query: How does the coronavirus differ from seasonal flu?

positive: Comprehensive overview of COVID-19 based on current evidence In December 2019, twenty-seven pneumonia patients with unknown causes originated in South China seafood market in Wuhan. The virus infection spread rapidly and swept through China in less than a month. Subsequently, the virus was proven a novel coronavirus and named SARS-CoV-2. The outbreak of novel coronavirus has been determined as a Public Health Emergency of International Concern (PHEIC) by WHO on January 31, 2020. Similar to other coronaviruses like the Middle East Respiratory Syndrome (MERS) CoV and Severe Acute Respiratory Syndrome (SARS) CoV, the novel coronavirus was reported to spread via respiratory droplets and close contact from human to human, which means the virus is highly infectious and dangerous. Unfortunately, till now the virus has spread to over 200 countries/territories/areas around the world and the Coronavirus Disease 2019 (COVID-19) outbreak is continuing to grow. Currently, information sharing and transparency are essential for risk assessment and epidemic control in all endemic areas. In this article, we compared SARS-CoV-2 with SARS-CoV and influenza virus, discussed current researching progress of COVID-19, including clinical characteristics, pathological changes, treatment measures, and so on.

positive: The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? OBJECTIVES: To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China. METHODS: Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. Comparisons between the viruses were made. RESULTS: Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally. CONCLUSIONS: We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.

positive: Temperature Decreases Spread Parameters of the New Covid-19 Case Dynamics (1) Background: The virulence of coronavirus diseases due to viruses like SARS-CoV or MERS-CoV decreases in humid and hot weather. The putative temperature dependence of infectivity by the new coronavirus SARS-CoV-2 or covid-19 has a high predictive medical interest. (2) Methods: External temperature and new covid-19 cases in 21 countries and in the French administrative regions were collected from public data. Associations between epidemiological parameters of the new case dynamics and temperature were examined using an ARIMA model. (3) Results: We show that, in the first stages of the epidemic, the velocity of contagion decreases with country- or region-wise temperature. (4) Conclusions: Results indicate that high temperatures diminish initial contagion rates, but seasonal temperature effects at later stages of the epidemy remain questionable. Confinement policies and other eviction rules should account for climatological heterogeneities, in order to adapt the public health decisions to possible geographic or seasonal gradients.

positive: Understanding the emerging coronavirus: what it means for health security and infection prevention

positive: First COVID-19 mortality case in Taiwan with bacterial co-infection by national surveillance of critically ill patients with influenza-negative pneumonia A 63-year-old diabetic smoker with alcoholism was the first mortality case of coronavirus disease 2019 (COVID-19) in Taiwan. As concurrently infected with Klebsiella pneumoniae and subsequently with Klebsiella aerogenes, he was exposed by a national survey of patients with critically influenza-negative pneumonia. We recommend COVID-19 screening for patients with severe flu-like syndrome and protecting health-care workers from being infected.

positive: Histopathology and genetic susceptibility in COVID-19 pneumonia BACKGROUND: The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. AIMS: To provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID-19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease. MATERIALS AND METHOD: We assessed the available early literature for histopathological patterns of COVID-19 pneumonia and underlying risk factors. RESULT: The histopathological spectrum of COVID-19 pneumonia includes variable patterns of epithelial damage, vascular complications, fibrosis and inflammation. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. DISCUSSION: While some risk factors and their potential role in COVID-19 pneumonia are increasingly recognized, little is known about the mechanisms behind episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. CONCLUSION: The answer to many of the remaining questions regarding COVID-19 pneumonia pathogenesis may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping.

positive: How Should the Rehabilitation Community Prepare for 2019-nCoV? With the novel coronavirus 2019 (2019-nCoV) pandemic spreading quickly in the United States and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so most of the world's population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it is currently mainly social distancing and infection control measures.

positive: Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey BACKGROUND: During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium. METHODS: From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR) and probable (positive influenza A antigen or culture) pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers. RESULTS: During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%), concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002) and a higher mortality rate (4% vs 0%, p = 0.06). Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications. CONCLUSION: Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.

positive: Potential of age distribution profiles for the prediction of COVID-19 infection origin in a patient group The COVID-19 pandemic is a serious and global public health concern. It is now well known that COVID-19 cases may result in mild symptoms leading to patient recovery. However, severity of infection, fatality rates, and treatment responses across different countries, age groups, and demographic groups suggest that the nature of infection is diverse, and a timely investigation of the same is needed for evolving sound treatment and preventive strategies. This paper reports an the analysis of age distribution patterns in six groups of Indian COVID-19 patient populations based on their likely geographical origin of infection viz. the United Kingdom, North America, the European Union, the Middle East, and Asian countries. It was observed that patient groups stratified in this way had a distinct age profile and that some of these groups e.g. patient groups from Asia, the European Union, and the United Kingdom formed a different cluster than those from North America, the Middle East, and other regions. Patient age profiles of a population were found to be highly predictive of the group they belong to, and there are indications of their distinct recovery and fatality rates across gender. Altogether this study provides a scalable framework to estimate the source of infection in a new population of COVID-19 patients with unknown origin. It is also concluded that greater public availability of age and other demographic profile details of patients may be helpful in gaining robust insights into COVID-19 infection origins. Datasets and scripts used in this work are shared at http://covid.sciwhylab.org.

positive: The WHO global influenza surveillance and response system (GISRS)—A future perspective In the centenary year of the devastating 1918‐19 pandemic, it seems opportune to reflect on the success of the WHO Global Influenza Surveillance and Response System (GISRS) initiated 70 years ago to provide early warning of changes in influenza viruses circulating in the global population to help mitigate the consequences of such a pandemic and maintain the efficacy of seasonal influenza vaccines. Three pandemics later and in the face of pandemic threats from highly pathogenic zoonotic infections by different influenza A subtypes, it continues to represent a model platform for global collaboration and timely sharing of viruses, reagents and information to forestall and respond to public health emergencies.

positive: Establishing seasonal and alert influenza thresholds in Morocco BACKGROUND: Several statistical methods of variable complexity have been developed to establish thresholds for influenza activity that may be used to inform public health guidance. We compared the results of two methods and explored how they worked to characterize the 2018 influenza season performance–2018 season. METHODS: Historical data from the 2005/2006 to 2016/2018 influenza season performance seasons were provided by a network of 412 primary health centers in charge of influenza like illness (ILI) sentinel surveillance. We used the WHO averages and the moving epidemic method (MEM) to evaluate the proportion of ILI visits among all outpatient consultations (ILI%) as a proxy for influenza activity. We also used the MEM method to evaluate three seasons of composite data (ILI% multiplied by percent of ILI with laboratory-confirmed influenza) as recommended by WHO. RESULTS: The WHO method estimated the seasonal ILI% threshold at 0.9%. The annual epidemic period began on average at week 46 and lasted an average of 18 weeks. The MEM model estimated the epidemic threshold (corresponding to the WHO seasonal threshold) at 1.5% of ILI visits among all outpatient consultations. The annual epidemic period began on week 49 and lasted on average 14 weeks. Intensity thresholds were similar using both methods. When using the composite measure, the MEM method showed a clearer estimate of the beginning of the influenza epidemic, which was coincident with a sharp increase in confirmed ILI cases. CONCLUSIONS: We found that the threshold methodology presented in the WHO manual is simple to implement and easy to adopt for use by the Moroccan influenza surveillance system. The MEM method is more statistically sophisticated and may allow a better detection of the start of seasonal epidemics. Incorporation of virologic data into the composite parameter as recommended by WHO has the potential to increase the accuracy of seasonal threshold estimation.

positive: A close look at the biology of SARS-CoV-2, and the potential influence of weather conditions and seasons on COVID-19 case spread BACKGROUND: There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus, respiratory syncytial virus, human metapneumovirus and influenza virus, in cold weather. The pattern of outbreak of the coronavirus disease 2019 (COVID-19) in China during the flu season is further proof that meteorological conditions may potentially influence the susceptibility of human populations to coronaviruses, a situation that may become increasingly evident as the current global pandemic of COVID-19 unfolds. MAIN BODY: A very rapid spread and high mortality rates have characterized the COVID-19 pandemic in countries north of the equator where air temperatures have been seasonally low. It is unclear if the currently high rates of COVID-19 infections in countries of the northern hemisphere will wane during the summer months, or if fewer people overall will become infected with COVID-19 in countries south of the equator where warmer weather conditions prevail through most of the year. However, apart from the influence of seasons, evidence based on the structural biology and biochemical properties of many enveloped viruses similar to the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 (aetiology of COVID-19), support the higher likelihood of the latter of the two outcomes. Other factors that may potentially impact the rate of virus spread include the effectiveness of infection control practices, individual and herd immunity, and emergency preparedness levels of countries. CONCLUSION: This report highlights the potential influence of weather conditions, seasons and non-climatological factors on the geographical spread of cases of COVID-19 across the globe.

positive: The application of DNA nucleotide footprint plotting in coronavirus Direct visualization of the key features of coronavirus genomes can lead to a better understanding of this virus as well as a method to distinguish this type of virus from others. The DNA nucleotide footprint plotter is a tool that makes it possible for straightforward visualization of the characteristics of viral genomes. It can also distinguish different gene types and gene structures. The current project provides a novel tool for biological studies that can contribute to breakthroughs in coronavirus diagnosis, treatment, and prevention.

positive: Will Coronavirus Disease 2019 Become Seasonal? This manuscript explores the question of the seasonality of severe acute respiratory syndrome coronavirus 2 by reviewing 4 lines of evidence related to viral viability, transmission, ecological patterns, and observed epidemiology of coronavirus disease 2019 in the Southern Hemispheres' summer and early fall.

positive: Coronavirus nCOVID-19: A Pandemic Disease and the Saudi precautions Now nCOVID-19 has a foothold in many countries, and the threat of a pandemic situation has risen. Recently a novel coronavirus (nCOVID-19) has first emerged in China, causing multiple symptoms in humans and closely related to those caused by SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). The nCOVID-19 has reported in Wuhan city of China has recently infected over six million people and at least 0.4 million confirmed deaths all over the world, while 2.8 million people has recovered from this deadly virus. Many instances of this respiratory syndrome coronavirus infection have already reported in more than 216 countries and territories. In contrast, the majority of cases reported in the USA, Brazil, Russia, Spain, UK, Italy, France and many more countries. In today's context, the coronavirus is one of the significant issues faced by the world with plenty of cases. In these circumstances, rapid reviews which recommended by WHO (World Health Organization), and these recommendations are very significant, helpful and cover current data with different preventive measures developed by the Saudi CDC (Saudi Centre for Disease Prevention and Control). This review article describes the possible modes of transmission so that proper preventive actions should be taking. Importantly, this work mentioned the animal reservoir through which may infect humans, and it must be identified to break the transmission chain. In additions, this review paper briefly discussed the spread of the coronavirus in the Arabian Peninsula and what precaution measures are in place by each country to limit the spreading of this virus. Taking into consideration the preventive measures by pharmacists as part of health care professions, however, the number of infected people, especially those with close contact with nCOVID-19 patients, are rise day by day and currently seems unstoppable.

positive: Characteristic CT findings distinguishing 2019 novel coronavirus disease (COVID-19) from influenza pneumonia OBJECTIVES: To investigate the different CT characteristics which may distinguish influenza from 2019 coronavirus disease (COVID-19). METHODS: A total of 13 confirmed patients with COVID-19 were enrolled from January 16, 2020, to February 25, 2020. Furthermore, 92 CT scans of confirmed patients with influenza pneumonia, including 76 with influenza A and 16 with influenza B, scanned between January 1, 2019, to February 25, 2020, were retrospectively reviewed. Pulmonary lesion distributions, number, attenuation, lobe predomination, margin, contour, ground-glass opacity involvement pattern, bronchial wall thickening, air bronchogram, tree-in-bud sign, interlobular septal thickening, intralobular septal thickening, and pleural effusion were evaluated in COVID-19 and influenza pneumonia cohorts. RESULTS: Peripheral and non-specific distributions in COVID-19 showed a markedly higher frequency compared with the influenza group (p < 0.05). Most lesions in COVID-19 showed balanced lobe localization, while in influenza pneumonia they were predominantly located in the inferior lobe (p < 0.05). COVID-19 presented a clear lesion margin and a shrinking contour compared with influenza pneumonia (p < 0.05). COVID-19 had a patchy or combination of GGO and consolidation opacities, while a cluster-like pattern and bronchial wall thickening were more frequently seen in influenza pneumonia (p < 0.05). The lesion number and attenuation, air bronchogram, tree-in-bud sign, interlobular septal thickening, and intralobular septal thickening were not significantly different between the two groups (all p > 0.05). CONCLUSIONS: Though viral pneumonias generally show similar imaging features, there are some characteristic CT findings which may help differentiating COVID-19 from influenza pneumonia. KEY POINTS: • CT can play an early warning role in the diagnosis of COVID-19 in the case of no epidemic exposure. • CT could be used for the differential diagnosis of influenza and COVID-19 with satisfactory accuracy. • COVID-19 had a patchy or combination of GGO and consolidation opacities with peripheral distribution and balanced lobe predomination.

positive: Immunohistochemical assessment of respiratory viruses in necropsy samples from lethal non-pandemic seasonal respiratory infections. BACKGROUND/AIM Acute respiratory infections are an important cause of childhood morbidity and mortality throughout the world, and viruses have often been reported to be an aetiological agent. This study aimed to identify respiratory viruses in paraffin-embedded samples of paediatric lung necropsy specimens, using immunohistochemistry on tissue microarray slides. METHODS Retrospective study in 200 lung tissue samples from children who had died from severe respiratory infections during 1985-2005. Immunoperoxidase assay was performed to detect the viruses that were most commonly associated with respiratory tract infections: influenza virus A (FLU A), influenza virus B (FLU B), respiratory syncytial virus (RSV), adenovirus (AdV) and parainfluenza virus (PIV) types 1, 2 and 3. RESULTS Viruses were detected in 71 (35.5%) cases. Most positive cases were observed in children younger than 6 months. In 42.3% of cases, only one virus was detected: 11 (36.7%) RSV; 7 (23.3%) AdV; 4 (13.3%) PIV2; 3 (10%) FLU A; 2 (6.7%) FLU B; 2 (6.7%) PIV3; and 1 (3.3%) PIV1. Co-infection with more than one virus was observed in 41 (57.7%) cases. No positive correlations were observed between the presence of viral antigens and seasonality of the infection, sex, age or histopathological findings. CONCLUSIONS Non-pandemic seasonal respiratory viruses are involved in a significant number of deaths in paediatric patients; these findings highlight the importance of laboratory investigation of these agents in patients hospitalised with severe acute respiratory infections.

positive: How coronavirus lockdowns stopped flu in its tracks

positive: [SARS-CoV-2 infection (COVID-19): what can we expect?] - Case numbers in China are clearly declining, case numbers in many European regions are no longer increasing exponentially.- Data on mortality from SARS-CoV-2 infection are contradictory; mortality is certainly lower than for SARS and MERS, but probably higher than for most seasonal flu outbreaks in recent years- The main complication of SARS-CoV-2 infection is pneumonia with development of acute respiratory distress syndrome (ARDS)- Asymptomatic and oligosymptomatic courses with virus shedding are not uncommon; they may be more frequent in children than in adults. Virus excretion in asymptomatic people and in the pre-symptomatic phase of an infection is relevant for transmission- An effective antiviral therapy has not yet been established. Steroids for anti-inflammatory therapy are not recommended- It is very important to prepare all actors in the health care system for a longer-term burden of inpatients and complications and to create the necessary capacities. Low-threshold diagnostic testing and rapid detection of infection chains remain essential for better control of the pandemic. An effective vaccine is urgent.

positive: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study BACKGROUND: Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. METHODS: We retrospectively retrieved data for paediatric patients (aged 0-16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. FINDINGS: From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5-38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir-ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. INTERPRETATION: Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. FUNDING: Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.

positive: Active surveillance documents rates of clinical care seeking due to respiratory illness BACKGROUND: Respiratory viral infections are a leading cause of disease worldwide. However, the overall community prevalence of infections has not been properly assessed, as standard surveillance is typically acquired passively among individuals seeking clinical care. METHODS: We conducted a prospective cohort study in which participants provided daily diaries and weekly nasopharyngeal specimens that were tested for respiratory viruses. These data were used to analyze healthcare seeking behavior, compared with cross‐sectional ED data and NYC surveillance reports, and used to evaluate biases of medically attended ILI as signal for population respiratory disease and infection. RESULTS: The likelihood of seeking medical attention was virus‐dependent: higher for influenza and metapneumovirus (19%‐20%), lower for coronavirus and RSV (4%), and 71% of individuals with self‐reported ILI did not seek care and half of medically attended symptomatic manifestations did not meet the criteria for ILI. Only 5% of cohort respiratory virus infections and 21% of influenza infections were medically attended and classifiable as ILI. We estimated 1 ILI event per person/year but multiple respiratory infections per year. CONCLUSION: Standard, healthcare‐based respiratory surveillance has multiple limitations. Specifically, ILI is an incomplete metric for quantifying respiratory disease, viral respiratory infection, and influenza infection. The prevalence of respiratory viruses, as reported by standard, healthcare‐based surveillance, is skewed toward viruses producing more severe symptoms. Active, longitudinal studies are a helpful supplement to standard surveillance, can improve understanding of the overall circulation and burden of respiratory viruses, and can aid development of more robust measures for controlling the spread of these pathogens.

positive: Comparison of Hospitalized Patients with pneumonia caused by COVID-19 and influenza A in children under 5 years Abstract Background Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to differentiate COVID-19 from other respiratory infectious diseases, such as influenza viruses. Methods This was a retrospective study. Two group of COVID-19 patients (n=57) and influenza A patients (n=59) were enrolled. We analyzed and compared their clinical manifestations, imaging characteristics and treatments. Results The proportions of cough (70.2%), fever (54.4%) and gastrointestinal symptoms (14.1%) in COVID-19 patients were lower than those of influenza A patients (98.3%, P<0.001; 84.7%, P<0.001; and 35.6%, P=0.007; respectively). In addition, COVID-19 patients showed significantly lower levels of leukocytes (7.87 vs. 9.89×109/L, P=0.027), neutrophils (2.43 vs. 5.16×109/L, P<0.001), C-reactive protein (CRP; 3.7 vs. 15.1mg/L, P=0.001) and procalcitonin (PCT; 0.09 vs. 0.68mm/h, P<0.001), while lymphocyte levels (4.58 vs. 3.56×109/L; P=0.006) were significantly higher compared with influenza A patients. In terms of CT imaging, ground-glass opacification in chest CT was more common in COVID-19 patients than in influenza A patients (42.1% vs. 15%, P=0.032). In contrast, consolidation was more common in influenza A patients (25%) than that in COVID-19 patients (5.2%, P=0.025). Conclusion The clinical manifestations and laboratory tests of COVID-19 children are milder than those of influenza A children under 5 years. Additionally, imaging results more commonly presented as ground-glass opacities in COVID-19 patients.

positive: Can the summer temperature drop COVID-19 cases? Abstract Objective In spite of huge global, national and local preventive measures including travel restriction, social distancing and quarantines, outbreak of novel coronavirus SARS-CoV-2 develops COVID-19 worldwide pandemic. SARS-CoV-2 emerging from Wuhan, China took only three months to cover > 200 countries worldwide by infecting more than 2.4 million people and killing more than 150000 people. Though, this infection at the early stage creates seasonal flu-like symptoms with a higher illness, it eventually causes a higher mortality. Epidemiological studies not only find the causes of many health issues, but also suggest preventive measures. This study aimed to see the link between environment temperature and COVID-19 cases. Study design The monthly average environment temperature (MAET) and various COVID-19 cases of a country were collected, and analyzed to see the relationship between these parameters. Methods Univariate analysis and statistical modeling were used to determine the relationship between environment temperature and different COVID-19 cases. Results This study found that the majorities of the countries having higher COVID-19 cases are located in the higher latitude (colder region) in the globe. As of 20th April data available, statistical analyses by various methods have found that strong negative correlations with statistical significance exist between MAET and several COVID-19 cases including total cases, active cases and cases per million of a country [Spearman correlation coefficients were -0.45, -0.42, and -0.50 for total cases, active cases and cases/per million, respectively]. Analysis by statistical log-linear regression model further supports that the chance of COVID-19 patients is fewer in warmer countries than in colder countries. Conclusion This pilot study proposes that cold environment may be an additional risk factor for COVID-19 cases.

positive: COVID-19: what is next for public health?

positive: The association between the seasonality of pediatric pandemic influenza virus outbreak and ambient meteorological factors in Shanghai BACKGROUND AND OBJECTIVES: The number of pediatric patients diagnosed with influenza types A and B is increasing annually, especially in temperate regions such as Shanghai (China). The onset of pandemic influenza viruses might be attributed to various ambient meteorological factors including temperature, relative humidity (Rh), and PM(1) concentrations, etc. The study aims to explore the correlation between the seasonality of pandemic influenza and these factors. METHODS: We recruited pediatric patients aged from 0 to 18 years who were diagnosed with influenza A or B from July 1st, 2017 to June 30th, 2019 in Shanghai Children’s Medical Centre (SCMC). Ambient meteorological data were collected from the Shanghai Meteorological Service (SMS) over the same period. The correlation of influenza outbreak and meteorological factors were analyzed through preliminary Pearson’s r correlation test and subsequent time-series Poisson regression analysis using the distributed lag non-linear model (DLNM). RESULTS: Pearson’s r test showed a statistically significant correlation between the weekly number of influenza A outpatients and ambient meteorological factors including weekly mean, maximum, minimum temperature and barometric pressure (P < 0.001), and PM(1) (P < 0.01). While the weekly number of influenza B outpatients was statistically significantly correlated with weekly mean, maximum and minimum temperature (P < 0.001), barometric pressure and PM(1) (P < 0.01), and minimum Rh (P < 0.05). Mean temperature and PM(1) were demonstrated to be the statistically significant variables in the DLNM with influenza A and B outpatients through time-series Poisson regression analysis. A U-shaped curve relationship was noted between the mean temperature and influenza A cases (below 15 °C and above 20 °C), and the risks increased for influenza B with mean temperature below 10 °C. PM(1) posed a risk after a concentration of 23 ppm for both influenza A and B. High PM(1), low and the high temperature had significant effects upon the number of influenza A cases, whereas low temperature and high PM(1) had significant effects upon the number of influenza B cases. CONCLUSION: This study indicated that mean temperature and PM(1) were the primary factors that were continually associated with the seasonality of pediatric pandemic influenza A and B and the recurrence in the transmission and spread of influenza viruses.

positive: Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.

positive: Seasonality of Respiratory Viral Infections The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

positive: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France. There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.

positive: Seasonality of Respiratory Viral Infections. The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

positive: A Comparison of Clinical and Chest CT Findings in Patients With Influenza A (H1N1) Virus Infection and Coronavirus Disease (COVID-19). OBJECTIVE. The purpose of this study was to compare clinical and chest CT findings in patients with influenza A (H1N1) pneumonia and coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Thirty patients with diagnosed influenza A (H1N1) virus infection (group A) and 30 patients with diagnosed COVID-19 (group B) were retrospectively enrolled in the present study. The clinical characteristics and chest CT findings of the two groups were compared. RESULTS. Fever, cough, expectoration, and dyspnea were the main symptoms in both groups with viral pneumonia, with cough and expectoration more frequently found in group A. Lymphopenia, an elevated C-reactive protein level, and an increased erythrocyte sedimentation rate were common laboratory test findings in the two groups. The median time from symptom onset to CT in group A and group B was 6 and 15 days, respectively, and the median total CT score of the pulmonary lobes involved was 6 and 13, respectively. Linear opacification, crazy-paving sign, vascular enlargement, were more common in group B. In contrast, bronchiectasis and pleural effusion were more common in group A. Other common CT features, including peripheral or peribronchovascular distribution, ground-glass opacities (GGOs), consolidation, subpleural line, air bronchogram, and bronchial distortion, did not show statistical significance. CONCLUSION. On CT, the significant differences between influenza A (H1N1) pneumonia and COVID-19 pneumonia were findings of linear opacification, crazy-paving sign, vascular enlargement, pleural thickening, and pleural effusion, which were more common in patients with COVID-19 pneumonia, and bronchiectasis and pleural effusion, which were more common in patients with influenza A (H1N1) pneumonia. Other imaging findings, including peripheral or peribronchovascular distribution, ground-glass opacities (GGO), consolidation, subpleural line, air bronchogram, and bronchial distortion, were not significantly different between the two patient groups.

positive: A novel presentation of COVID-19 via community acquired infection

positive: Evaluating Symptom Severity of Influenza Viral Infection Using the Influenza Patient-reported Outcomes Instrument (FLU-PRO) in a Healthy Human Challenge Model BACKGROUND: To apply the validated FLU-PRO scoring method to assess influenza symptom severity in a healthy human challenge model. METHODS: Healthy adults admitted to the NIH Clinical Center (Day -1) underwent a 9 day inpatient quarantine after intranasal challenge with H1N1pdm (Day 0). Participants completed the 32 item FLU-PRO diary twice daily for 14 days to assess presence and severity of symptoms across six body systems. Secondary analyses included descriptive statistics to examine FLU-PRO scores over the course of illness and analysis of variance to compare severity scores on Day 3 post-challenge by viral shedding, and pre-challenge hemagglutinin and neuraminidase inhibition (HAI and NAI) titers. RESULTS: 61 of 65 subjects reported symptoms (Days: Median 5, Mean 6 ± 7), of which 37 (61%) had viral shedding. Pre-challenge, 39 (64%) and 10 (16%) subjects had low (<40) HAI and NAI titers, respectively. Mean daily FLU-PRO symptom severity domain and total scores are shown in Figure 1. Symptoms were present across all FLU-PRO domains from Day 1 post-challenge. Nose, throat, body, and GI symptoms reached peak severity at Day 3, followed by chest and eye symptoms at Day 4. Subjects with viral shedding had significantly higher mean FLU-PRO scores compared with those without, except for Eye and GI domains (P < .05); mean FLU-PRO scores were significantly higher for subjects with low NAI titer (P < .05) across all domains. No significant differences were observed between HAI titer groups. FLU-PRO scores of the low HAI-low NAI group (n = 10) were significantly higher (more severe) than the other two groups (P < .05) ((high HAI-low NAI (n = 22), low HAI-high NAI (n = 29)). CONCLUSION: The FLU-PRO can be used to track symptom onset, severity, and recovery from influenza infection in clinical research. In this challenge study, scores were responsive to change even in mild disease and distinguished known clinical subgroups. The use of NAI as an independent predictor of influenza disease severity was also supported. Funded by NCI Contract No. HHSN261200800001E and in part by the Intramural Research Program of the NIH, NIAID DISCLOSURES: J. L. Poon, Evidera: Employee, Salary; R. Yu, Evidera: Employee, Salary; N. K. Leidy, Evidera: Employee, Salary

positive: Chest Computed Tomography Findings in COVID-19 and Influenza: A Narrative Review OBJECTIVE: The COVID-19 pandemic and annual influenza epidemic are responsible for thousands of deaths globally. With a similarity in clinical as well as laboratory findings, there is a need to differentiate these two conditions on chest CT scan. This paper attempts to use existing literature to draw out differences in chest CT findings in COVID-19 and influenza. METHODS: A search was conducted using PubMed. 17 original studies on chest CT findings in COVID-19 and influenza were identified for full-text review and data analysis. Findings. COVID-19 and influenza share similar chest CT findings. The differences found show that COVID-19 ground-glass opacities are usually peripherally located with the lower lobes being commonly involved, while influenza has a central, peripheral, or random distribution usually affecting the five lobes. Vascular engorgement, pleural thickening, and subpleural lines were reported in COVID-19 patients. In contrast, pneumomediastinum and pneumothorax were reported only in studies on influenza. Conclusion and Relevance. COVID-19 and influenza have overlapping chest CT features with few differences which can assist in telling apart the two pathologies. Additional studies are needed to further define the differences and degree between COVID-19 and influenza.

positive: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic. A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.

positive: Measuring COVID-19 and Influenza in the Real World via Person-Generated Health Data Background: Since the beginning of the COVID-19 pandemic data from smartphones and connected sensors has been used to learn about symptoms presentation and management outside the clinic walls. However, reports on the validity of such data are still sparse, especially when it comes to symptom progression and relevance of wearable sensors. Objective: To understand the relevance of Person-GeneratedHealth Data (PGHD) as a means for early detection, monitoring and management of COVID-19 in everyday life. This includes quantifying prevalence and progression of symptoms from self-reports as well as changes in activity and physiological parameters continuously measured from wearable sensors, and contextualizing findings for COVID-19 patients with those from cohorts of flu patients. Design, Setting, and Participants: Retrospective digital cohort study of individuals with a self-reported positive SARS-CoV-2 or influenza test followed over the period 2019-12-02 to2020-04-27. Three cohorts were derived: Patients who self-reported being diagnosed with flu prior to the SARS-CoV-2 pandemic (N=6270, of which 1226 also contributed sensorPGHD); Patients who reported being diagnosed with flu during the SARS-CoV-2 pandemic (N=426, of which 85 also shared sensor PGHD); and patients who reported being diagnosed withCOVID-19 (N=230, of which sensor PGHD was available for 41).The cohorts were derived from a large-scale digital participatory surveillance study designed to track Influenza-like Illness(ILI) incidence and burden over time. Exposures: Self-reported demographic data, comorbidities, and symptoms experienced during a diagnosed ILI episode, including SARS-CoV-2.Physiological and behavioral parameters measured daily from commercial wearable sensors, includingResting Heart Rate (RHR), total step count, and nightly sleep hours. Main Outcomes and Measures: We investigated the percent-age of individuals experiencing symptoms of a given type (e.g.shortness of breath) across demographic groups and over time. We examined illness duration, and care seeking behavior, and how RHR, step count, and nightly sleep hours deviated from expected behavior on healthy days over the course of the infection episode. Results: Self-reported symptoms of COVID-19 present differently from flu. COVID-19 cases tended to last longer than flu(median of 12 vs. 9 days), are uniquely characterized by chest pain/pressure, shortness of breath, and anosmia. The fraction of elevated RHR measurements collected daily from commercial wearable devices rise significantly in the 2 days surrounding ILI symptoms onset, but does not appear to do so in a way specific to COVID-19. Steps lost due to COVID-19 persists for longer. Conclusion and Relevance: PGHD can be a valid source of longitudinal real world data to detect and monitor COVID-19-related symptoms and behaviors at population scale. PGHD may provide continuous, near realtime feedback to intervention effectiveness that otherwise requires waiting for symptoms to develop into contacts with the healthcare system. It has also the potential to increase pre-test probability of other downstream diagnostics. To effectively leverage PGHD for participatory surveillance it is crucial to invest in the creation of trusted, long-term communication channels with individuals through whichdata can be efficiently collected, consented, and contextualized,while protecting the privacy of individuals and ultimately facilitating the transition in and out of care.

positive: Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1 Background Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. Research question The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. Study Design and Methods This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. Results The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the COVID-19 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao 2/Fio 2 of 198.2 mm Hg in the COVID-19 cohort was significantly higher than the Pao 2/Fio 2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). Interpretation There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

positive: Clinical features of COVID-19 and influenza: A comparative study on Nord Franche-Comte cluster Clinical descriptions about influenza-like illnesses (ILI) in COVID-19 seem non-specific. We aimed to compare the clinical features of COVID-19 and influenza. We retrospectively investigated the clinical features and outcomes of confirmed cases of COVID-19 and influenza in Nord Franche-Comté Hospital between February 26(th) and March 14(th) 2020. We used SARS-CoV-2 RT-PCR and influenza virus A/B RT-PCR in respiratory samples to confirm the diagnosis. We included 124 patients. The mean age was 59(±19[19-98]) years with 69% female. 70 patients with COVID-19 and 54 patients with influenza A/B. Regarding age, sex and comorbidities, no differences were found between the two groups except a lower Charlson index in COVID-19 group (2[±2.5] vs 3[±2.4],p=0.003). Anosmia (53% vs 17%,p<0.001), dysgeusia (49% vs 20%,p=0.001), diarrhea (40% vs 20%,p=0.021), frontal headache (26% vs 9%,p=0.021) and bilateral cracklings sounds (24% vs 9%,p=0.034) were statistically more frequent in COVID-19. Sputum production (52% vs 29%,p=0.010), dyspnea (59% vs 34%,p=0.007), sore throat (44% vs 20%,p=0.006), conjunctival hyperhemia (30% vs 4%,p<0.001), tearing (24% vs 6%,p=0.004), vomiting (22% vs 3%,p=0.001) and rhonchi sounds (17% vs 1%,p=0.002) were more frequent with influenza infection. We described several clinical differences which can help the clinicians during the co-circulation of influenza and SARS-CoV-2.

positive: Chapter 8 Big Data Applications in Health Sciences and Epidemiology Abstract There is growing concern about our preparedness for controlling the spread of pandemics such as H1N1 Influenza. The dynamics of epidemic spread in large-scale populations are very complex. Further, human behavior, social contact networks, and pandemics are closely intertwined and evolve as the epidemic spread. Individuals’ changing behaviors in response to public policies and their evolving perception of how an infectious disease outbreak is unfolding can dramatically alter normal social interactions. Effective planning and response strategies must take these complicated interactions into account. Mathematical models are key to understanding the spread of epidemics. In this chapter, we discuss a recent approach of diffusion in network models for studying the complex dynamics of epidemics in large-scale populations. Analyzing these models leads to very challenging computational problems. Further, using these models for forecasting epidemic spread and developing public health policies leads to issues that are characteristic of big data applications. The chapter describes the state of the art in computational and big data epidemiology.

positive: A COVID-19 Epidemiological Model for Community and Policy Maker Use An epidemiological model for COVID-19 was developed and implemented in MATLAB/GNU Octave for use by public health practitioners, policy makers and the general public. The model distinguishes four stages in the disease: infected, sick, seriously sick, and better. The model was preliminarily parameterized based on observations of the spread of the disease. The model is consistent with a mortality rate of 1.5 %. Preliminary simulations with the model indicate that concepts such as"herd immunity"and"flattening the curve"are highly misleading in the context of this virus. Public policies based on these concepts are inadequate to protect the population. Only reducing the R0 of the virus below 1 is an effective strategy for maintaining the death burden of COVID-19 within the normal range of seasonal flu. As R0 values estimated with the model range from 2.82 worldwide outside of China and 3.83 in the Western world in late February - early March 2020, this means social distancing with effectiveness greater than 65 % (worldwide) or 75 % (Western world) are needed to combat the virus successfully.

positive: Mask crisis during the COVID-19 outbreak On December 31, 2019, the World Health Organization (WHO) reported a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. As of February 29, 2020, the National Health Commission of China has reported 79,389 confirmed cases of SARS-CoV-2 infection in 34 provinces. The masks can be used to block respiratory transmission from human to human, and are an effective way to control influenza. It is, therefore, necessary to wear a mask when respiratory infectious diseases are prevalent. China has a population of 1.4 billion. Assuming that two-thirds of the people in China must wear a mask every day, the daily demand for masks will reach 900 million. The Chinese government has taken many measures to solve these problems. Additionally, more measures should be taken to properly dispose of mask garbage. Although the outbreak originated in China, person-to-person transmission of SARS-CoV-2 has been confirmed, which means that it can be spread to anywhere in the world if prevention measures fail. The issues regarding face mask shortages and garbage in China, therefore, deserve worldwide attention.

positive: Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study BACKGROUND: A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong. We examined the effect of these interventions and behavioural changes of the public on the incidence of COVID-19, as well as on influenza virus infections, which might share some aspects of transmission dynamics with COVID-19. METHODS: We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (R(t)) for COVID-19 and influenza A H1N1 to estimate changes in transmissibility over time. Attitudes towards COVID-19 and changes in population behaviours were reviewed through three telephone surveys done on Jan 20–23, Feb 11–14, and March 10–13, 2020. FINDINGS: COVID-19 transmissibility measured by R(t) has remained at approximately 1 for 8 weeks in Hong Kong. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% CI 34–53%) reduction in transmissibility in the community, from an estimated R(t) of 1·28 (95% CI 1·26–1·30) before the start of the school closures to 0·72 (0·70–0·74) during the closure weeks. Similarly, a 33% (24–43%) reduction in transmissibility was seen based on paediatric hospitalisation rates, from an R(t) of 1·10 (1·06–1·12) before the start of the school closures to 0·73 (0·68–0·77) after school closures. Among respondents to the surveys, 74·5%, 97·5%, and 98·8% reported wearing masks when going out, and 61·3%, 90·2%, and 85·1% reported avoiding crowded places in surveys 1 (n=1008), 2 (n=1000), and 3 (n=1005), respectively. INTERPRETATION: Our study shows that non-pharmaceutical interventions (including border restrictions, quarantine and isolation, distancing, and changes in population behaviour) were associated with reduced transmission of COVID-19 in Hong Kong, and are also likely to have substantially reduced influenza transmission in early February, 2020. FUNDING: Health and Medical Research Fund, Hong Kong.

positive: Do Humidity and Temperature Impact the Spread of the Novel Coronavirus?

positive: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 80,000 confirmed infections and 2,700 fatalities (as of Feb 27, 2020). Imported cases and transmission clusters of various sizes have been reported globally suggesting a pandemic is likely. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.

positive: Transmission Dynamics of COVID-19 and Impact on Public Health Policy In this work we construct a mathematical model for the transmission and spread of coronavirus disease 2019 or COVID-19. Our model features delay terms to account for (a) the time lapse or latency period between contracting the disease and displaying symptoms, and (b) the time lag in testing patients for the virus due to the limited numbers of testing facilities currently available. We find that the delay introduces a significant disparity between the actual and reported time-trajectories of cases in a particular region. Specifically, the reported case histories lag the actual histories by a few days. Hence, to minimize the spread of the disease, lockdowns and similarly drastic social isolation measures need to be imposed some time before the reported figures are approaching their peak values. We then account for the social reality that lockdowns can only be of a limited duration in view of practical considerations. We find that the most effective interval for imposing such a limited-time lockdown is one where the midpoint of the lockdown period coincides with the actual peak of the spread of the disease in the absence of the lockdown. We further show that the true effectivity of imposing a lockdown may be misrepresented and grossly underestimated by the reported case trajectories in the days following the action.

positive: A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses World Health Organization has declared the ongoing outbreak of coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern. The virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. Human infection with SARS-CoV-2 leads to a wide range of clinical manifestations ranging from asymptomatic, mild, moderate to severe. The severe cases present with pneumonia, which can progress to acute respiratory distress syndrome. The outbreak provides an opportunity for real-time tracking of an animal coronavirus that has just crossed species barrier to infect humans. The outcome of SARS-CoV-2 infection is largely determined by virus-host interaction. Here, we review the discovery, zoonotic origin, animal hosts, transmissibility and pathogenicity of SARS-CoV-2 in relation to its interplay with host antiviral defense. A comparison with SARS-CoV, Middle East respiratory syndrome coronavirus, community-acquired human coronaviruses and other pathogenic viruses including human immunodeficiency viruses is made. We summarize current understanding of the induction of a proinflammatory cytokine storm by other highly pathogenic human coronaviruses, their adaptation to humans and their usurpation of the cell death programmes. Important questions concerning the interaction between SARS-CoV-2 and host antiviral defence, including asymptomatic and presymptomatic virus shedding, are also discussed.

positive: Coronavirus, as a source of pandemic pathogens The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary The genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.

positive: COVID-19 pneumonia: CT findings of 122 patients and differentiation from influenza pneumonia OBJECTIVES: To investigate the clinical and chest CT characteristics of COVID-19 pneumonia and explore the radiological differences between COVID-19 and influenza. MATERIALS AND METHODS: A total of 122 patients (61 men and 61 women, 48 ± 15 years) confirmed with COVID-19 and 48 patients (23 men and 25 women, 47 ± 19 years) confirmed with influenza were enrolled in the study. Thin-section CT was performed. The clinical data and the chest CT findings were recorded. RESULTS: The most common symptoms of COVID-19 were fever (74%) and cough (63%), and 102 patients (83%) had Wuhan contact. Pneumonia in 50 patients with COVID-19 (45%) distributed in the peripheral regions of the lung, while it showed mixed distribution in 26 patients (74%) with influenza (p = 0.022). The most common CT features of the COVID-19 group were pure ground-glass opacities (GGO, 36%), GGO with consolidation (51%), rounded opacities (35%), linear opacities (64%), bronchiolar wall thickening (49%), and interlobular septal thickening (66%). Compared with the influenza group, the COVID-19 group was more likely to have rounded opacities (35% vs. 17%, p = 0.048) and interlobular septal thickening (66% vs. 43%, p = 0.014), but less likely to have nodules (28% vs. 71%, p < 0.001), tree-in-bud sign (9% vs. 40%, p < 0.001), and pleural effusion (6% vs. 31%, p < 0.001). CONCLUSIONS: There are significant differences in the CT manifestations of patients with COVID-19 and influenza. Presence of rounded opacities and interlobular septal thickening, with the absence of nodules and tree-in-bud sign, and with the typical peripheral distribution, may help us differentiate COVID-19 from influenza. KEY POINTS: • Typical CT features of COVID-19 include pure ground-glass opacities (GGO), GGO with consolidation, rounded opacities, bronchiolar wall thickening, interlobular septal thickening, and a peripheral distribution. • Presence of rounded opacities and interlobular septal thickening, with the absence of nodules and tree-in-bud sign, and with the typical peripheral distribution, may help us differentiate COVID-19 from influenza.

positive: Prior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children Background: Children have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS). Methods: This cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup). Findings: SARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55.6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66.9 -100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection. Interpretation: Prior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection.

positive: A new transmission route for the propagation of the SARS-CoV-2 coronavirus We explore here how variation in the SARS-CoV-2 virus tropism could influence epidemic spread. We use a compartmental model fit to the existing data. The model indicates that Wuhan quarantine measures were effective but that alternative virus forms (gut tropism) and a second propagation route (through environment) was present. For Singapore and Shenzhen region the secondary route does not seem to be active yet. Adequate prevention measures taking into account both routes should be implemented.

positive: Potential Immunotherapeutic Targets For Hypoxia Due to COVI-FLU. The world is currently embroiled in a pandemic of coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel betacoronavirus SARS-CoV-2. The severity of COVID-19 disease ranges from asymptomatic to fatal acute respiratory distress syndrome (ARDS). In few patients, the disease undergoes phenotypic differentiation between 7-14 days of acute illness, either resulting in full recovery or symptom escalation. However, the mechanism of such variation is not clear, but the facts suggest that patient's immune status, co-morbidities, and the systemic effects of the viral infection (potentially depending on the SARS-CoV-2 strain involved) play a key role. Subsequently, patients with the most severe symptoms tend to have poor outcomes, manifest severe hypoxia, and possess elevated levels of pro-inflammatory cytokines (including IL-1β, IL-6, IFN-γ, and TNF-α) along with elevated levels of the anti-inflammatory cytokine IL-10, marked lymphopenia, and elevated neutrophil-to-lymphocyte ratios. Based on the available evidence, we propose a mechanism wherein SARS-CoV-2 infection induces direct organ damage while also fueling an IL-6-mediated cytokine release syndrome (CRS) and hypoxia, resulting in escalating systemic inflammation, multi-organ damage, and end-organ failure. Elevated IL-6 and hypoxia together predisposes patients to pulmonary hypertension, and the presence of asymptomatic hypoxia in COVID-19 further compounds this problem. Due to the similar downstream mediators, we discuss the potential synergistic effects and systemic ramifications of SARS-CoV-2 and influenza virus during co-infection, a phenomenon we have termed "COVI-Flu." Additionally, the differences between CRS and cytokine storm are highlighted. Finally, novel management approaches, clinical trials, and therapeutic strategies toward both SARS-CoV-2 and COVI-Flu infection are discussed, highlighting host response optimization and systemic inflammation reduction.

positive: [Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia]. The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.

positive: Towards a data-driven characterization of behavioral changes induced by the seasonal flu In this work, we aim to determine the main factors driving self-initiated behavioral changes during the seasonal flu. To this end, we designed and deployed a questionnaire via Influweb, a Web platform for participatory surveillance in Italy, during the 2017 − 18 and 2018 − 19 seasons. We collected 599 surveys completed by 434 users. The data provide socio-demographic information, level of concerns about the flu, past experience with illnesses, and the type of behavioral changes voluntarily implemented by each participant. We describe each response with a set of features and divide them in three target categories. These describe those that report i) no (26%), ii) only moderately (36%), iii) significant (38%) changes in behaviors. In these settings, we adopt machine learning algorithms to investigate the extent to which target variables can be predicted by looking only at the set of features. Notably, 66% of the samples in the category describing more significant changes in behaviors are correctly classified through Gradient Boosted Trees. Furthermore, we investigate the importance of each feature in the classification task and uncover complex relationships between individuals’ characteristics and their attitude towards behavioral change. We find that intensity, recency of past illnesses, perceived susceptibility to and perceived severity of an infection are the most significant features in the classification task and are associated to significant changes in behaviors. Overall, the research contributes to the small set of empirical studies devoted to the data-driven characterization of behavioral changes induced by infectious diseases.

positive: Estimating the Early Outbreak Cumulative Incidence of COVID-19 in the United States: Three Complementary Approaches Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the weekly incidence of COVID-19. Unfortunately, a lack of systematic testing across the United States (US) due to equipment shortages and varying testing strategies has hindered the usefulness of the reported positive COVID-19 case counts. We introduce three complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 during the early outbreak in each state in the US as well as in New York City, using a combination of excess influenza-like illness reports, COVID-19 test statistics, and COVID-19 mortality reports. Instead of relying on an estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our three approaches, there is a consistent conclusion that estimated state-level COVID-19 symptomatic case counts from March 1 to April 4, 2020 varied from 5 to 50 times greater than the official positive test counts. Nationally, our estimates of COVID-19 symptomatic cases in the US as of April 4 have a likely range of 2.2 to 5.1 million cases, with possibly as high as 8.1 million cases, up to 26 times greater than the cumulative confirmed cases of about 311,000. Extending our method to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 6.0 to 12.2 million, which compares with 1.5 million positive test counts. Our approaches demonstrate the value of leveraging existing influenza-like-illness surveillance systems during the flu season for measuring the burden of new diseases that share symptoms with influenza-like-illnesses. Our methods may prove useful in assessing the burden of COVID-19 during upcoming flu seasons in the US and other countries with comparable influenza surveillance systems.

positive: On the global trends and spread of the COVID-19 outbreak: preliminary assessment of the potential relation between location-specific temperature and UV index The novel coronavirus, since its first outbreak in December, has, up till now, affected approximately 114,542 people across 115 countries. Many international agencies are devoting efforts to enhance the understanding of the evolving COVID-19 outbreak on an international level, its influences, and preparedness. At present, COVID-19 appears to affect individuals through person-to-person means, like other commonly found cold or influenza viruses. It is widely known and acknowledged that viruses causing influenza peak during cold temperatures and gradually subside in the warmer temperature, owing to their seasonality. Thus, COVID-19, due to its regular flu-like symptoms, is also expected to show similar seasonality and subside as the global temperatures rise in the northern hemisphere with the onset of spring. Despite these speculations, however, the systematic analysis in the global perspective of the relation between COVID-19 spread and meteorological parameters is unavailable. Here, by analyzing the region- and city-specific affected global data and corresponding meteorological parameters, we show that there is an optimum range of temperature and UV index strongly affecting the spread and survival of the virus, whereas precipitation, relative humidity, cloud cover, etc. have no effect on the virus. Unavailability of pharmaceutical interventions would require greater preparedness and alert for the effective control of COVID-19. Under these conditions, the information provided here could be very helpful for the global community struggling to fight this global crisis. It is, however, important to note that the information presented here clearly lacks any physiological evidences, which may merit further investigation. Thus, any attempt for management, implementation, and evaluation strategies responding to the crisis arising due to the COVID-19 outbreak must not consider the evaluation presented here as the foremost factor.

positive: The effects of regional climatic condition on the spread of COVID-19 at global scale The pandemic outbreak of the novel coronavirus epidemic disease (COVID-19) is spreading like a diffusion-reaction in the world and almost 208 countries and territories are being affected around the globe. It became a sever health and socio-economic problem, while the world has no vaccine to combat this virus. This research aims to analyze the connection between the fast spread of COVID-19 and regional climate parameters over a global scale. In this research, we collected the data of COVID-19 cases from the time of 1st reported case to the 5th June 2020 in different affected countries and regional climatic parameters data from January 2020 to 5th June 2020. It was found that most of the countries located in the relatively lower temperature region show a rapid increase in the COVID-19 cases than the countries locating in the warmer climatic regions despite their better socio-economic conditions. A correlation between metrological parameters and COVID-19 cases was observed. Average daylight hours are correlated to total the COVID-19 cases with a coefficient of determination of 0.42, while average high-temperature shows a correlation of 0.59 and 0.42 with total COVID-19 cases and death cases respectively. The finding of the study will help international health organizations and local administrations to combat and well manage the spread of COVID-19.

positive: Performance of suspected influenza case definitionbefore and during the COVID-19 pandemic Background: The influenza-related burden remains high and the COVID-19 pandemic may difficult its accurate surveillance. This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. Methods: A cross-sectional analysis of a cohort study took place and cases fulfilling the suspected case criteria (n = 20,511), and with laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection were analyzed. Results: A high sensitivity and modest specificity were documented, and this later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the Area Under the Receiver Operating Characteristics among the analyzed periods. Conclusions: The evaluated case definition remains to be a cost-effective alternative to identify patients who may benefit from influenza-specific antiviral drugs, even during the COVID-19 global outbreak.

positive: Mask crisis during the COVID-19 outbreak. On December 31, 2019, the World Health Organization (WHO) reported a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. As of February 29, 2020, the National Health Commission of China has reported 79,389 confirmed cases of SARS-CoV-2 infection in 34 provinces. The masks can be used to block respiratory transmission from human to human, and are an effective way to control influenza. It is, therefore, necessary to wear a mask when respiratory infectious diseases are prevalent. China has a population of 1.4 billion. Assuming that two-thirds of the people in China must wear a mask every day, the daily demand for masks will reach 900 million. The Chinese government has taken many measures to solve these problems. Additionally, more measures should be taken to properly dispose of mask garbage. Although the outbreak originated in China, person-to-person transmission of SARS-CoV-2 has been confirmed, which means that it can be spread to anywhere in the world if prevention measures fail. The issues regarding face mask shortages and garbage in China, therefore, deserve worldwide attention.

positive: Collateral Benefits on Other Respiratory Infections during Fighting COVID-19 Abstract Purpose: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan. Method: We collected week-case data of severe influenza, invasive Streptococcus pneumoniae disease and death toll from pneumonia among 25 calendar weeks of the influenza season for four years (2016-2020), which were reported to Taiwan CDC. Trend and slope differences between years were compared. Result: A downturn trend of severe influenza, invasive Streptococcus pneumoniae disease and the death toll from pneumonia per week in 2019/2020 season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential COVID-19 outbreak in Taiwan. Conclusions: Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive Streptococcus pneumoniae disease activity, and the death toll from pneumonia reported to CDC in Taiwan.

positive: COVID-19: Tracking the Pandemic with A Simple Curve Approximation Tool (SCAT) Background In the current COVID-19 pandemic, much focus is put on 'flattening the curve'. This epidemiological 'curve' refers to the cases versus time graph, which shows the rise of a disease to its peak before descending. The aim in a pandemic is to flatten this curve by reducing the peak and spreading out the timeline. However, the models used to predict this curve are often not clearly outlined, no model parameters are given, and models are not tested against real data. This lack of detail makes it difficult to recreate the curve. What is much needed is a simple tool for approximating the curve to allow ideas to be tested and comparisons made. Methods This work presents a Simple Curve Approximation Tool (SCAT) which can be used by anyone. This tool allows the user to approximate and draw the curve and allows testing of assumptions, trajectories and the wildly varying figures reported in the media. The mathematics behind SCAT is clearly outlined here but understanding of this is not required. SCAT is provided online as a downloadable MS Excel workbook with some sample cases shown. Throughout this work, the parameters used are specified so that all results can be easily reproduced. Findings Although not intended as a prediction tool, SCAT has achieved less than 0.5 % error in short-term forward prediction. It also shows a very significant improvement on the pandemic exponential approximations found throughout media reporting. As a comparison tool, it highlights obvious differences between COVID-19 and other diseases, such as influenza, and between countries at different stages of the pandemic (China, Italy and the UK are used here for demonstration purposes). Interpretation SCAT allows for quick approximation of the curve and creates meaningful comparisons and understandable visualisations for COVID-19 and other diseases. Funding None.

positive: Characteristic CT findings distinguishing 2019 novel coronavirus disease (COVID-19) from influenza pneumonia OBJECTIVES: To investigate the different CT characteristics which may distinguish influenza from 2019 coronavirus disease (COVID-19). METHODS: A total of 13 confirmed patients with COVID-19 were enrolled from January 16, 2020, to February 25, 2020. Furthermore, 92 CT scans of confirmed patients with influenza pneumonia, including 76 with influenza A and 16 with influenza B, scanned between January 1, 2019, to February 25, 2020, were retrospectively reviewed. Pulmonary lesion distributions, number, attenuation, lobe predomination, margin, contour, ground-glass opacity involvement pattern, bronchial wall thickening, air bronchogram, tree-in-bud sign, interlobular septal thickening, intralobular septal thickening, and pleural effusion were evaluated in COVID-19 and influenza pneumonia cohorts. RESULTS: Peripheral and non-specific distributions in COVID-19 showed a markedly higher frequency compared with the influenza group (p < 0.05). Most lesions in COVID-19 showed balanced lobe localization, while in influenza pneumonia they were predominantly located in the inferior lobe (p < 0.05). COVID-19 presented a clear lesion margin and a shrinking contour compared with influenza pneumonia (p < 0.05). COVID-19 had a patchy or combination of GGO and consolidation opacities, while a cluster-like pattern and bronchial wall thickening were more frequently seen in influenza pneumonia (p < 0.05). The lesion number and attenuation, air bronchogram, tree-in-bud sign, interlobular septal thickening, and intralobular septal thickening were not significantly different between the two groups (all p > 0.05). CONCLUSIONS: Though viral pneumonias generally show similar imaging features, there are some characteristic CT findings which may help differentiating COVID-19 from influenza pneumonia. KEY POINTS: â¢ CT can play an early warning role in the diagnosis of COVID-19 in the case of no epidemic exposure. â¢ CT could be used for the differential diagnosis of influenza and COVID-19 with satisfactory accuracy. â¢ COVID-19 had a patchy or combination of GGO and consolidation opacities with peripheral distribution and balanced lobe predomination.

positive: Air Pollution and temperature are associated with increased COVID-19 incidence: a time series study OBJECTIVES: Although the COVID-19 is known to cause by human-to-human transmission, it remains largely unclear whether ambient air pollutants and meteorological parameters could promote its transmission. METHODS: A retrospective study is conducted to study whether air quality index (AQI), four ambient air pollutants (PM(2.5), PM(10), NO(2) and CO) and five meteorological variables (daily temperature, highest temperature, lowest temperature, temperature difference and sunshine duration) could increase COVID-19 incidence in Wuhan and XiaoGan between Jan 26(th) to Feb 29(th) in 2020. RESULTS: First, a significant correlation was found between COVID-19 incidence and AQI in both Wuhan (R(2) = 0.13, p < 0.05) and XiaoGan (R(2) = 0.223, p < 0.01). Specifically, among four pollutants, COVID-19 incidence was prominently correlated with PM(2.5) and NO(2) in both cities. In Wuhan, the tightest correlation was observed between NO(2) and COVID-19 incidence (R(2) = 0.329, p < 0.01). In XiaoGan, in addition to the PM(2.5) (R(2) = 0.117, p < 0.01) and NO(2) (R(2) = 0.015, p < 0.05), a notable correlation was also observed between the PM(10) and COVID-19 incidence (R(2) = 0.105, p < 0.05). Moreover, temperature is the only meteorological parameter that constantly correlated well with COVID-19 incidence in both Wuhan and XiaoGan, but in an inverse correlation (p < 0.05). CONCLUSIONS: AQI, PM(2.5), NO(2), and temperature are four variables that could promote the sustained transmission of COVID-19.

positive: Patterns of seasonal and pandemic influenza-associated health care and mortality in Ontario, Canada BACKGROUND: Mathematical and statistical models are used to project the future time course of infectious disease epidemics and the expected future burden on health care systems and economies. Influenza is a particularly important disease in this context because it causes annual epidemics and occasional pandemics. In order to forecast health care utilization during epidemics—and the effects of hospitalizations and deaths on the contact network and, in turn, on transmission dynamics—modellers must make assumptions about the lengths of time between infection, visiting a physician, being admitted to hospital, leaving hospital, and death. More reliable forecasts could be be made if the distributions of times between these types of events (“delay distributions”) were known. METHODS: We estimated delay distributions in the province of Ontario, Canada, between 2006 and 2010. To do so, we used encrypted health insurance numbers to link 1.34 billion health care billing records to 4.27 million hospital inpatient stays. Because the four year period we studied included three typical influenza seasons and the 2009 influenza pandemic, we were able to compare the delay distributions in non-pandemic and pandemic settings. We also estimated conditional probabilities such as the probability of hospitalization within the year if diagnosed with influenza. RESULTS: In non-pandemic [pandemic] years, delay distribution medians (inter-quartile ranges) were: Service to Admission 6.3 days (0.1–17.6 days) [2.4 days (-0.3–13.6 days)], Admission to Discharge 3 days (1.4–5.9 days) [2.6 days (1.2–5.1 days)], Admission to Death 5.3 days (2.1–11 days) [6 days (2.6–13.1 days)]. (Service date is defined as the date, within the year, of the first health care billing that included a diagnostic code for influenza-like-illness.) Among individuals diagnosed with either pneumonia or influenza in a given year, 19% [16%] were hospitalized within the year and 3% [2%] died in hospital. Among all individuals who were hospitalized, 10% [12%] were diagnosed with pneumonia or influenza during the year and 5% [5%] died in hospital. CONCLUSION: Our empirical delay distributions and conditional probabilities should help facilitate more accurate forecasts in the future, including improved predictions of hospital bed demands during influenza outbreaks, and the expected effects of hospitalizations on epidemic dynamics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-7369-x) contains supplementary material, which is available to authorized users.

positive: Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

positive: Going viral – Covid-19 impact assessment: A perspective beyond clinical practice In the realm of infectious diseases, a global outbreak is a worst-case scenario In the past, outbreaks such as plague, Spanish flu, severe acute respiratory syndrome, and H1N1 (swine flu) have caused great human suffering The novel coronavirus, christened as Covid-19, is a zoonotic disease which originated from the Wuhan province in China and spread like wildfire killing people and devastating the global economy Mammoth efforts are still on to control this viral strain from further spread Cities have been blocked, air travel banned, ships have been quarantined, and panic-stricken people have been evacuated from China As Covid-19 continues to ravage countries across the globe, this article is an effort to provide an overview of the impact of Covid-19 and tickle wits of intellectuals to think how easily a nanometer organism can virtually bring down superpowers of the world

positive: Climate impact on spreading of airborne infectious diseases: Complex network based modeling of climate influences on influenza like illnesses In this study we combined a wide range of data sets to simulate the outbreak of an airborne infectious disease that is directly transmitted from human to human. The basis is a complex network whose structures are inspired by global air traffic data (from openflights.org) containing information about airports, airport locations, direct flight connections and airplane types. Disease spreading inside every node is realized with a Susceptible-Exposed-Infected-Recovered (SEIR) compartmental model. Disease transmission rates in our model are depending on the climate environment and therefore vary in time and from node to node. To implement the correlation between water vapor pressure and influenza transmission rate [J. Shaman, M. Kohn, Proc. Natl. Acad. Sci. 106, 3243 (2009)], we use global available climate reanalysis data (WATCH-Forcing-Data-ERA-Interim, WFDEI). During our sensitivity analysis we found that disease spreading dynamics are strongly depending on network properties, the climatic environment of the epidemic outbreak location, and the season during the year in which the outbreak is happening.

positive: Excess registered deaths in England and Wales during the COVID-19 pandemic, March 2020 to May 2020 Official counts of COVID-19 deaths have been criticized for potentially including people who did not die of COVID-19 but merely died with COVID-19. I address that critique by fitting a generalized additive model to weekly counts of all deaths registered in England and Wales during the 2010s. The model produces baseline rates of death registrations expected without the COVID-19 pandemic, and comparing those baselines to recent counts of registered deaths exposes the emergence of excess deaths late in March 2020. By April's end, England and Wales registered 45,300 $\pm$ 3200 excess deaths of adults aged 45+. Through 22 May, the last day of available all-deaths data, 56,600 $\pm$ 4400 were registered (about 53% of which were of men). Both the ONS's corresponding count of 43,205 death certificates which mention COVID-19, and the Department of Health and Social Care's count of 33,671 deaths, are appreciably less, implying that their counting methods have underestimated, not overestimated, the pandemic's true death toll. If underreporting rates have held steady during May, about 59,000 direct and indirect COVID-19 deaths might have been registered through the end of May but not yet publicly reported in full.

positive: The costs of preventing the spread of respiratory infection in family physician offices: a threshold analysis BACKGROUND: Influenza poses concerns about epidemic respiratory infection. Interventions designed to prevent the spread of respiratory infection within family physician (FP) offices could potentially have a significant positive influence on the health of Canadians. The main purpose of this paper is to estimate the explicit costs of such an intervention. METHODS: A cost analysis of a respiratory infection control was conducted. The costs were estimated from the perspective of provincial government. In addition, a threshold analysis was conducted to estimate a threshold value of the intervention's effectiveness that could generate potential savings in terms of averted health-care costs by the intervention that exceed the explicit costs. The informational requirements for these implicit costs savings are high, however. Some of these elements, such as the cost of hospitalization in the event of contacting influenza, and the number of patients passing through the physicians' office, were readily available. Other pertinent points of information, such as the proportion of infected people who require hospitalization, could be imported from the existing literature. We take an indirect approach to calculate a threshold value for the most uncertain piece of information, namely the reduction in the probability of the infection spreading as a direct result of the intervention, at which the intervention becomes worthwhile. RESULTS: The 5-week intervention costs amounted to a total of $52,810.71, or $131,094.73 prorated according to the length of the flu season, or $512,729.30 prorated for the entire calendar year. The variable costs that were incurred for this 5-week project amounted to approximately $923.16 per participating medical practice. The (fixed) training costs per practice were equivalent to $73.27 for the 5-week intervention, or $28.14 for 13-week flu season, or $7.05 for an entire one-year period. CONCLUSION: Based on our conservative estimates for the direct cost savings, there are indications that the outreach facilitation intervention program would be cost effective if it can achieve a reduction in the probability of infection on the order of 0.83 (0.77, 1.05) percentage points. A facilitation intervention initiative tailored to the environment and needs of the family medical practice and walk-in clinics is of promise for improving respiratory infection control in the physicians' offices.

positive: Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19) Importance: Coronavirus disease 2019 (COVID-19) infection has resulted in a global crisis. Investigating the potential association of climate and seasonality with the spread of this infection could aid in preventive and surveillance strategies. Objective: To examine the association of climate with the spread of COVID-19 infection. Design, Setting, and Participants: This cohort study examined climate data from 50 cities worldwide with and without substantial community spread of COVID-19. Eight cities with substantial spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) were compared with 42 cities that have not been affected or did not have substantial community spread. Data were collected from January to March 10, 2020. Main Outcomes and Measures: Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020. Climate data (latitude, mean 2-m temperature, mean specific humidity, and mean relative humidity) were obtained from ERA-5 reanalysis. Results: The 8 cities with substantial community spread as of March 10, 2020, were located on a narrow band, roughly on the 30° N to 50° N corridor. They had consistently similar weather patterns, consisting of mean temperatures of between 5 and 11 °C, combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m3). There was a lack of substantial community establishment in expected locations based on proximity. For example, while Wuhan, China (30.8° N) had 3136 deaths and 80â¯757 cases, Moscow, Russia (56.0° N), had 0 deaths and 10 cases and Hanoi, Vietnam (21.2° N), had 0 deaths and 31 cases. Conclusions and Relevance: In this study, the distribution of substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements was consistent with the behavior of a seasonal respiratory virus. Using weather modeling, it may be possible to estimate the regions most likely to be at a higher risk of substantial community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.

positive: The Epidemic Severity Index: Estimating Relative Local Severity of Novel Disease Outbreaks Determining the severity of a novel pathogen in the early stages is difficult in the absence of reliable data. The pattern of outbreaks for COVID-19 across the globe have differed markedly above and below +40N latitudes, suggesting very different levels of severity, but countries worldwide have implemented the same lockdown strategies. Existing methods for estimating severity appear not to have been useful in informing strategic decisions, possibly due to mismatches between the data required and those available, overly sophisticated methods with undesirable biases, or perhaps confusion and uncertainly generated by the wide range of estimates these methods produced early on. The Epidemic Severity Index (ESI) is a simple, robust method for estimating the local severity of novel epidemic outbreaks using early and widely-available data and that does not depend on any estimated values. ESI allows rapid, meaningful comparisons across territories that can be tracked as the outbreaks unfold. The ESI quantifies severity relative to a parameterised baseline rather than attempting to estimate values for infection fatality rates, case fatality rates or transmission rates. The relative nature of the ESI sidesteps any problems of confidence associated with absolute rate estimation methods and offers immediate practical strategic value.

positive: Political Intrusions into the International Health Regulations Treaty and Its Impact on Management of Rapidly Emerging Zoonotic Pandemics: What History Tells Us For a large number of health care providers world-wide, the coronavirus disease 2019 (COVID-19) pandemic is their first experience in population-based care. In past decades, lower population densities, infectious disease outbreaks, epidemics, and pandemics were rare and driven almost exclusively by natural disasters, predatory animals, and war. In the early 1900s, Sir William Osler first advanced the knowledge of zoonotic diseases that are spread from reservoir animals to human animals. Once rare, they now make up 71% or more of new diseases. Globally, zoonotic spread occurs for many reasons. Because the human population has grown in numbers and density, the spread of these diseases accelerated though rapid unsustainable urbanization, biodiversity loss, and climate change. Furthermore, they are exacerbated by an increasing number of vulnerable populations suffering from chronic deficiencies in food, water, and energy. The World Health Organization (WHO) and its International Health Regulation (IHR) Treaty, organized to manage population-based diseases such as Influenza, severe acute respiratory syndrome (SARS), H1N1, Middle East respiratory syndrome (MERS), HIV, and Ebola, have failed to meet population-based expectations. In part, this is due to influence from powerful political donors, which has become most evident in the current COVID-19 pandemic. The global community can no longer tolerate an ineffectual and passive international response system, nor tolerate the self-serving political interference that authoritarian regimes and others have exercised over the WHO. In a highly integrated globalized world, both the WHO with its IHR Treaty have the potential to become one of the most effective mechanisms for crisis response and risk reduction world-wide. Practitioners and health decision-makers must break their silence and advocate for a stronger treaty, a return of the WHO’s singular global authority, and support highly coordinated population-based management. As Osler recognized, his concept of “one medicine, one health” defines what global public health is today.

positive: Room Temperature Isothermal Colorimetric Padlock Probe Rolling Circle Amplification for Viral RNA Detection Seasonal flu and pandemics, which account for millions of infections and hundreds of thousands of deaths, require rapid and reliable detection mechanisms for preventive and therapeutic measures. Current methods of viral detection have limitations in speed, accuracy, accessibility, and usability. This project presents a novel, widely applicable viral diagnosis that uses a modified version of the traditional rolling circle amplification (RCA) to be sensitive, specific, direct, colorimetric, and operable at room temperature. We are specifically aiming to detect SARS-CoV-2, Influenza A (H1N1pdm09), and Influenza B (Victoria Lineage). Results using synthetic viral DNA sequences show that the diagnostic test could take as fast as 30 minutes and detect up to picomolar concentrations of DNA strands. The next step for this project is to test the assay with synthetic viral RNA to verify the results. We envision that the implementation of this type of diagnostic test could allow faster responses to outbreaks of related viruses and quicker societal recovery.

positive: Could enhanced influenza and pneumococcal vaccination programs help limit the potential damage from SARS-CoV-2 to fragile health systems of southern hemisphere countries this winter?

positive: Excess cases of influenza-like illnesses synchronous with coronavirus disease (COVID-19) epidemic, France, March 2020 Several French regions where coronavirus disease (COVID-19) has been reported currently show a renewed increase in ILI cases in the general practice-based Sentinelles network. We computed the number of excess cases by region from 24 February to 8 March 2020 and found a correlation with the number of reported COVID-19 cases so far. The data suggest larger circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the French population than apparent from confirmed cases.

positive: Knowledge of novel coronavirus (SARS-COV-2) among a Georgian population Introduction Georgia confirmed its first case of SARS-COV-2 infection on February 26, 2020 and by March 31, a total of 110 cases have been reported. Limited understanding about epidemics can lead to panic and disrupt public health efforts to contain transmission. It is important to understand perceptions of the population regarding the disease. This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus among Georgian population, including health care workers (HCWs). Materials and methods The online survey was conducted using a Facebook advertisement. The target was the whole country and the language used was Georgian. We collected information on demographic data, knowledge of the disease, including perceived differences between coronavirus and influenza. We also included questions to capture the populations perceptions about government preparedness to combat the new coronavirus. Results The survey was open for three days (March 2-4, 2020). 5228 participants completed the survey. Of these, 40.3% were 25-45 years old, 58.2% were female, 20.7% had university degree and 10.3% were HCWs. For 25.8% of respondents, COVID-19 and influenza are the same diseases; 10.9% did not know if they are different. The majority correctly identified the transmission route and symptoms (96.9% and 98.0%, respectively). 19.1% think that Georgia is ready for COVID 19 epidemic, while according to 55% the county is not ready, but HCWs are trying hard to respond properly. For 18% response is inadequate. There was no difference in knowledge between HCWs, non-HCWs and unemployed. 20% of HCWs as well as other study subjects believe that SARS-COV-2 vaccine and medications do exist but are simply not available in Georgia. Conclusion Given that information regarding coronavirus is changing very rapidly, the need to reach people with time-sensitive educational messages as well as prevention strategies is vital.

positive: The epidemiology and clinical characteristics of co-infection of SARS-CoV-2 and influenza viruses in patients during COVID-19 outbreak In this study, we performed a single-centred study of 307 SARS-CoV-2 infected patients. It was found that co-infection of SARS-CoV-2 and influenza virus was common during COVID-19 outbreak. And patients co-infected with SARS-CoV-2 and influenza B virus have a higher risk of developing poor outcomes so a detection of both viruses was recommended during COVID-19 outbreak. This article is protected by copyright. All rights reserved.

positive: An Introduction to COVID-19 A novel coronavirus (CoV) named ‘2019-nCoV’ or ‘2019 novel coronavirus’ or ‘COVID-19’ by the World Health Organization (WHO) is in charge of the current outbreak of pneumonia that began at the beginning of December 2019 near in Wuhan City, Hubei Province, China [1–4]. COVID-19 is a pathogenic virus. From the phylogenetic analysis carried out with obtainable full genome sequences, bats occur to be the COVID-19 virus reservoir, but the intermediate host(s) has not been detected till now.

positive: Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis Abstract Objective To better inform efforts to treat and control the current outbreak with a comprehensive characterization of COVID-19. Methods We searched PubMed, EMBASE, Web of Science, and CNKI (Chinese Database) for studies published as of March 2, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2 . Publication bias was assessed using Egger's test. Results 43 studies involving 3600 patients were included. Among COVID-19 patients, fever (83.3% [95% CI 78.4–87.7]), cough (60.3% [54.2–66.3]), and fatigue (38.0% [29.8–46.5]) were the most common clinical symptoms. The most common laboratory abnormalities were elevated C-reactive protein (68.6% [58.2–78.2]), decreased lymphocyte count (57.4% [44.8–69.5]) and increased lactate dehydrogenase (51.6% [31.4–71.6]). Ground-glass opacities (80.0% [67.3–90.4]) and bilateral pneumonia (73.2% [63.4–82.1]) were the most frequently reported findings on computed tomography. The overall estimated proportion of severe cases and case-fatality rate (CFR) was 25.6% (17.4–34.9) and 3.6% (1.1–7.2), respectively. CFR and laboratory abnormalities were higher in severe cases, patients from Wuhan, and older patients, but CFR did not differ by gender. Conclusions The majority of COVID-19 cases are symptomatic with a moderate CFR. Patients living in Wuhan, older patients, and those with medical comorbidities tend to have more severe clinical symptoms and higher CFR.

positive: Coherence of Influenza Surveillance Data across Different Sources and Age Groups, Beijing, China, 2008-2015 Influenza is active during the winter and spring in the city of Beijing, which has a typical temperate climate with four clear distinct seasons. The clinical and laboratory surveillance data for influenza have been used to construct critical indicators for influenza activities in the community, and previous studies have reported varying degrees of association between laboratory-confirmed influenza specimens and outpatient consultation rates of influenza-like illness in subtropical cities. However, few studies have reported on this issue for cities in temperate regions, especially in developing countries. Furthermore, the mechanism behind age-specific seasonal epidemics remains unresolved, although it has been widely discussed. We utilized a wavelet analysis method to monitor the coherence of weekly percentage of laboratory-confirmed influenza specimens with the weekly outpatient consultation rates of influenza-like illness in Beijing, China. We first examined the seasonal pattern of laboratory-confirmed cases of influenza A (subtyped into seasonal A(H1N1) and A(H3N2) and pandemic virus A(H1N1) pdm09) and influenza B separately within the period from 2008–2015; then, we detected the coherence of clinical and laboratory surveillance data in this district, specially examining weekly time series of age-specific epidemics of influenza-like illnesses in the whole study period for three age categories (age 0–5, 5–15 and 25–60). We found that influenza A and B were both active in winter but were not always seasonally synchronous in Beijing. Synchronization between age ranges was found in most epidemic peaks from 2008–2015. Our findings suggested that peaks of influenza-like illness in individuals aged 0–5 and 5–15 years consistently appeared ahead of those of adults, implying the possibility that schoolchildren may lead epidemic fluctuations.

positive: Pollen Explains Flu-Like and COVID-19 Seasonality Current models for flu-like epidemics insufficiently explain multi-cycle seasonality. Meteorological factors alone do not predict seasonality, given substantial climate differences between countries that are subject to flu-like epidemics or COVID-19. Pollen is documented to be antiviral and allergenic, play a role in immuno-activation, and seems to create a bio-aerosol lowering the reproduction number of flu-like viruses. Therefore, we hypothesize that pollen may explain the seasonality of flu-like epidemics including COVID-19. We tested the Pollen-Flu Seasonality Theory for 2016-2020 flu-like seasons, including COVID-19, in The Netherlands with its 17 million inhabitants. We combined changes in flu-like incidence per 100K/Dutch citizens (code: ILI) with weekly pollen counts and meteorological data for the same period. Finally, a discrete, predictive model is tested using pollen and meteorological threshold values displaying inhibitory effects on flu-like incidence. We found a highly significant inverse association of r(224)= -.38 between pollen and changes in flu-like incidence corrected for incubation period, confirming our expectations for the 2019/2020 COVID-19 season. We found that our predictive model has the highest inverse correlation with changes in flu-like incidence of r(222) = -.48 (p < .001) when pollen thresholds of 610 total pollen grains/m3 per week, 120 allergenic pollen grains/m3 per week, and a solar radiation threshold of 510 J/cm2 are passed. The passing of at least the pollen thresholds, preludes the beginning and end of flu-like seasons. Solar radiation is a supportive factor, temperature makes no difference, and relative humidity associates even with flu-like incidence increases. We conclude that pollen is a predictor for the inverse seasonality of flu-like epidemics including COVID-19, and solar radiation is a co-inhibitor. The observed seasonality of COVID-19 during Spring, suggests that COVID-19 may revive in The Netherlands after week 33, the start being preceded by the relative absence of pollen, and follows standard pollen-flu seasonality patterns.

positive: Coronavirus Disease 2019 (COVID-19) and Pregnancy: Responding to a Rapidly Evolving Situation As the world confronts coronavirus disease 2019 (COVID-19), an illness caused by yet another emerging pathogen (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), obstetric care providers are asking what this means for pregnant women. The global spread has been swift, and many key questions remain. The case-fatality rate for persons cared for in the United States and whether asymptomatic persons transmit the virus are examples of questions that need to be answered to inform public health control measures. There are also unanswered questions specific to pregnant women, such as whether pregnant women are more severely affected and whether intrauterine transmission occurs. Although guidelines for pregnant women from the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention have been rapidly developed based on the best available evidence, additional information is critically needed to inform key decisions, such as whether pregnant health care workers should receive special consideration, whether to temporarily separate infected mothers and their newborns, and whether it is safe for infected women to breastfeed. Some current recommendations are well supported, based largely on what we know from seasonal influenza: patients should avoid contact with ill persons, avoid touching their face, cover coughs and sneezes, wash hands frequently, disinfect contaminated surfaces, and stay home when sick. Prenatal clinics should ensure all pregnant women and their visitors are screened for fever and respiratory symptoms, and symptomatic women should be isolated from well women and required to wear a mask. As the situation with COVID-19 rapidly unfolds, it is critical that obstetricians keep up to date.

positive: Next-generation influenza vaccines: opportunities and challenges Seasonal influenza vaccines lack efficacy against drifted or pandemic influenza strains. Developing improved vaccines that elicit broader immunity remains a public health priority. Immune responses to current vaccines focus on the haemagglutinin head domain, whereas next-generation vaccines target less variable virus structures, including the haemagglutinin stem. Strategies employed to improve vaccine efficacy involve using structure-based design and nanoparticle display to optimize the antigenicity and immunogenicity of target antigens; increasing the antigen dose; using novel adjuvants; stimulating cellular immunity; and targeting other viral proteins, including neuraminidase, matrix protein 2 or nucleoprotein. Improved understanding of influenza antigen structure and immunobiology is advancing novel vaccine candidates into human trials.

positive: Pathogenicity and transmissibility of 2019-nCoV—A quick overview and comparison with other emerging viruses Abstract A zoonotic coronavirus, tentatively labeled as 2019-nCoV by the World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.

positive: COVID-19 created chaos across the globe: Three novel quarantine epidemic models The latest version of human coronavirus said to be COVID-19 came out as a sudden pandemic disease within human population and in the absence of vaccination and proper treatment till date, it daunting threats heavily to human lives, infecting more than 12, 11, 214 people and death more than 67, 666 people in 208 countries across the globe as on April 06, 2020, which is highly alarming. When no treatment or vaccine is available till date and to avoid COVID-19 to be transmitted in the community, social distancing is the only way to prevent the disease, which is well taken into account in our novel epidemic models as a special compartment, that is, home isolation. Based on the transmitting behaviour of COVID-19 in the human population, we develop three quarantine models of this pandemic taking into account the compartments: susceptible population, immigrant population, home isolation population, infectious population, hospital quarantine population, and recovered population. Local and global asymptotic stability is proved for all the three models. Extensive numerical simulations are performed to establish the analytical results with suitable examples. Our research reveals that home isolation and quarantine to hospitals are the two pivot force-control policies under the present situation when no treatment is available for this pandemic.

positive: On the Centenary of the Spanish Flu: Being Prepared for the Next Pandemic

positive: [Be alert to superposed effect of seasonal influenza while fighting against COVID-19]. COVID-19 continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the COVID-19 epidemic.

positive: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020. Importance Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.

positive: On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management As the Coronavirus (COVID-19) expands its impact from China, expanding its catchment into surrounding regions and other countries, increased national and international measures are being taken to contain the outbreak. The placing of entire cities in ‘lockdown’ directly affects urban economies on a multi-lateral level, including from social and economic standpoints. This is being emphasised as the outbreak gains ground in other countries, leading towards a global health emergency, and as global collaboration is sought in numerous quarters. However, while effective protocols in regard to the sharing of health data is emphasised, urban data, on the other hand, specifically relating to urban health and safe city concepts, is still viewed from a nationalist perspective as solely benefiting a nation’s economy and its economic and political influence. This perspective paper, written one month after detection and during the outbreak, surveys the virus outbreak from an urban standpoint and advances how smart city networks should work towards enhancing standardization protocols for increased data sharing in the event of outbreaks or disasters, leading to better global understanding and management of the same.

positive: Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital. METHODS: Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray™ Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections. RESULTS: Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.

positive: Awareness, Attitudes, and Actions Related to COVID-19 Among Adults With Chronic Conditions at the Onset of the U.S. Outbreak: A Cross-sectional Survey BACKGROUND: The evolving outbreak of coronavirus disease 2019 (COVID-19) is requiring social distancing and other measures to protect public health. However, messaging has been inconsistent and unclear. OBJECTIVE: To determine COVID-19 awareness, knowledge, attitudes, and related behaviors among U.S. adults who are more vulnerable to complications of infection because of age and comorbid conditions. DESIGN: Cross-sectional survey linked to 3 active clinical trials and 1 cohort study. SETTING: 5 academic internal medicine practices and 2 federally qualified health centers. PATIENTS: 630 adults aged 23 to 88 years living with 1 or more chronic conditions. MEASUREMENTS: Self-reported knowledge, attitudes, and behaviors related to COVID-19. RESULTS: A fourth (24.6%) of participants were “very worried” about getting the coronavirus. Nearly a third could not correctly identify symptoms (28.3%) or ways to prevent infection (30.2%). One in 4 adults (24.6%) believed that they were “not at all likely” to get the virus, and 21.9% reported that COVID-19 had little or no effect on their daily routine. One in 10 respondents was very confident that the federal government could prevent a nationwide outbreak. In multivariable analyses, participants who were black, were living below the poverty level, and had low health literacy were more likely to be less worried about COVID-19, to not believe that they would become infected, and to feel less prepared for an outbreak. Those with low health literacy had greater confidence in the federal government response. LIMITATION: Cross-sectional study of adults with underlying health conditions in 1 city during the initial week of the COVID-19 U.S. outbreak. CONCLUSION: Many adults with comorbid conditions lacked critical knowledge about COVID-19 and, despite concern, were not changing routines or plans. Noted disparities suggest that greater public health efforts may be needed to mobilize the most vulnerable communities. PRIMARY FUNDING SOURCE: National Institutes of Health.

positive: Co-infection with Influenza A and COVID-19 COVID-19, also called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China. It has caused significant morbidity and mortality worldwide and has been declared a global pandemic by the WHO. Influenza occurs mainly during the winter, with the burden of disease determined by several factors, including the effectiveness of the vaccine that season, the characteristics of the circulating viruses, and how long the season lasts. We describe the case of a 66-year-old woman who was diagnosed with influenza A and COVID-19 co-infection. LEARNING POINTS: COVID-19 can co-occur with other viral infections. Some of these co-infections have active treatments, while supportive treatment is the mainstay of treatment for others.

positive: COVID-19 versus seasonal influenza 2019-2020: USA Severe mitigation efforts in the USA to reduce the incidence of COVID-19 infections have led to a massive rise in unemployment, social disruption, and appear to be leading to a severe economic depression. In contrast, no such interventions were regarded as necessary to manage seasonal influenza in 2019-2020. Another mitigation approach is proposed for COVID-19 that would allow society to function and yet should still be effective.

positive: Modeling the impact of mass influenza vaccination and public health interventions on COVID-19 epidemics with limited detection capability The emerging coronavirus SARS-CoV-2 has caused a COVID-19 pandemic. SARS-CoV-2 causes a generally mild, but sometimes severe and even life-threatening infection, known as COVID-19. Currently, there exist no effective vaccines or drugs and, as such, global public authorities have so far relied upon non pharmaceutical interventions (NPIs). Since COVID-19 symptoms are aspecific and may resemble a common cold, if it should come back with a seasonal pattern and coincide with the influenza season, this would be particularly challenging, overwhelming and straining the healthcare systems, particularly in resource-limited contexts, and would increase the likelihood of nosocomial transmission. In the present study, we devised a mathematical model focusing on the treatment of people complaining of influenza-like-illness (ILI) symptoms, potentially at risk of contracting COVID-19 or other emerging/re-emerging respiratory infectious agents during their admission at the health-care setting, who will occupy the detection kits causing a severe shortage of testing resources. The model is used to assess the effect of mass influenza vaccination on the spread of COVID-19 and the other respiratory pathogens in the case of a coincidence of the outbreak with the influenza season. Here, we show that increasing influenza vaccine uptake or enhancing the public health interventions would facilitate the management of respiratory outbreaks coinciding with the peak flu season, especially, compensate the shortage of the detection resources. However, how to increase influenza vaccination coverage rate remains challenging. Public health decision- and policy-makers should adopt evidence-informed strategies to improve influenza vaccine uptake.

positive: Symptomatology during seasonal coronavirus infections in children is associated with viral and bacterial co-detection Lower respiratory tract symptoms during seasonal coronavirus infections in children are associated with RSV co-detection and increased levels of Haemophilus and Fusobacterium species.

positive: An Aberration Detection-Based Approach for Sentinel Syndromic Surveillance of COVID-19 and Other Novel Influenza-Like Illnesses Coronavirus Disease 2019 (COVID-19) has emerged as a significant global concern, triggering harsh public health restrictions in a successful bid to curb its exponential growth. As discussion shifts towards relaxation of these restrictions, there is significant concern of second-wave resurgence. The key to managing these outbreaks is early detection and intervention, and yet there is significant lag time associated with usage of laboratory confirmed cases for surveillance purposes. To address this, syndromic surveillance can be considered to provide a timelier alternative for first-line screening. Existing syndromic surveillance solutions are however typically focused around a known disease and have limited capability to distinguish between outbreaks of individual diseases sharing similar syndromes. This poses a challenge for surveillance of COVID-19 as its active periods are tend to overlap temporally with other influenza-like illnesses. In this study we explore performing sentinel syndromic surveillance for COVID-19 and other influenza-like illnesses using a deep learning-based approach. Our methods are based on aberration detection utilizing autoencoders that leverages symptom prevalence distributions to distinguish outbreaks of two ongoing diseases that share similar syndromes, even if they occur concurrently. We first demonstrate that this approach works for detection of outbreaks of influenza, which has known temporal boundaries. We then demonstrate that the autoencoder can be trained to not alert on known and well-managed influenza-like illnesses such as the common cold and influenza. Finally, we applied our approach to 2019–2020 data in the context of a COVID-19 syndromic surveillance task to demonstrate how implementation of such a system could have provided early warning of an outbreak of a novel influenza-like illness that did not match the symptom prevalence profile of influenza and other known influenza-like illnesses.

positive: Susceptible supply limits the role of climate in the early SARS-CoV-2 pandemic Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios based on known coronavirus biology. We find that while variations in weather may be important for endemic infections, during the pandemic stage of an emerging pathogen the climate drives only modest changes to pandemic size. A preliminary analysis of non-pharmaceutical control measures indicates that they may moderate the pandemic-climate interaction via susceptible depletion. Our findings suggest, without effective control measures, strong outbreaks are likely in more humid climates and summer weather will not substantially limit pandemic growth.

positive: Likelihood of survival of coronavirus disease 2019

positive: Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.

positive: Is there a clinical difference between influenza A and B virus infections in hospitalized patients?: Results after routine polymerase chain reaction point-of-care testing in the emergency room from 2017/2018 PURPOSE: The clinical presentation, complications and mortality in molecularly confirmed influenza A and B infections were analyzed. METHODS: This retrospective observational single-centre study included all influenza positive patients older than 18 years who were hospitalized and treated at the flu isolation ward during 2017/2018. The diagnosis was based on point-of-care tests with the Alere(TM). RESULTS: Of the 396 patients tested positive for influenza, 24.2% had influenza A and 75.8% influenza B. Influenza A patients were younger (median age 67.5 years vs. 77 years, p < 0.001), were more often smokers (27.7% vs. 16.8%, p = 0.021), had chronic pulmonary diseases more frequently (39.6% vs. 26.3%, p = 0.013), presented with a higher body temperature (38.6 °C vs. 38.3 °C, p = 0.004), leucocyte count (8 G/L vs. 6.8 G/L, p = 0.002), C‑reactive protein (CRP) level (41 mg/l vs. 23 mg/l, p < 0.001) and had dyspnea more often (41.7% vs. 28%, p = 0.012). Influenza B patients had an underlying chronic kidney disease in 37% vs. 18.8% (p < 0.001) and presented with vomiting on admission more frequently (21.7% vs. 11.5%, p = 0.027). Influenza A patients were admitted for 8 days vs. 7 days (p = 0.023). There were no differences in the rate of complications; however, 22 (5.6%) patients died during the hospital stay. The in-hospital mortality was higher in influenza A patients (8.3% vs 4.7%, p = 0.172). CONCLUSION: Some differences were found between influenza A and B virus infections but symptoms were overlapping, which necessitates polymerase chain reaction point-of-care testing for accurate diagnosis. Influenza A was a more severe disease than influenza B during the period 2017/2018.

positive: Population based estimates of comorbidities affecting risk for complications from COVID-19 in the US We used 2017 Behavioral Risk Factor Surveillance System (BRFSS) data (N=444,649) to estimate the proportion of US adults who report comorbidities that suggest heightened risk of complications from COVID-19. Co-morbidities included cardiovascular disease, chronic obstructive pulmonary disease (COPD), diabetes, asthma, hypertension, and/or cancer other than skin, based on data from China. Overall 45.4% (95% CI 45.1-45.7) of adults reported any of the 6 comorbidities, increasing from 19.8% (19.1-20.4) for ages 18-29 years to 80.7% (79.5-81.8) for ages 80+ years. State rates ranged from 37.3% (36.2-38.5) in Utah to 58.7% (57.0-60.4) in West Virginia. Rates also varied by race/ethnicity, health insurance status, and employment. Excluded were residents of nursing homes or assisted living facilities. Although almost certainly an underestimate of all adults at risk due to these exclusions, these results should help in estimating healthcare needs for adults with COVID-19 complications living in the community.

positive: COVID-19 in Brazil: advantages of a socialized unified health system and preparation to contain cases The outbreak of new coronavirus disease 2019 (COVID-19) reported for the first time in Wuhan, China in late December 2019 have rapidly spread to other countries and it was declared on January 30, 2020 as a public health emergency of international concern (PHEIC) by the World Health Organization. Before the first COVID-19 cases were reported in Brazil, several measures have been implemented including the adjustment of legal framework to carry out isolation and quarantine. As the cases increased significantly, new measures, mainly to reduce mortality and severe cases, have also been implemented. Rapid and robust preparedness actions have been undertaken in Brazil while first cases have not yet been identified in Latin-American. The outcome of this early preparation should be analyzed in future studies.

positive: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.

positive: An open call for influenza vaccination pending the new wave of COVID‐19 In their study, Yue et al. reported influenza co-infection among COVID-19 patients as 57.3%. The study included a period of January 12-February 21, 2020 in Wuhan, China. We have recently detected this rate as 0.54% in Turkey. This difference between rates of co-infection can be explained by the seasonality of the influenza virus. Our study included the period of March 10-May 10. Another study from Wuhan, including the period of 28 January-29 February 2020, reported the rate of influenza co-infection among critically ill COVID-19 patients as 49.5%. Zhu et al. reported 2.7% influenza co-infections among COVID-19 patients, in their study from January 22-February 2. Two studies from USA reported low rates of 0.08% in March 16-April 20, and 0.9% in March 3-March 25. Therefore, studies from the influenza season reported very high rates of co-infection. When the COVID-19 came to Europe and America, the influenza season was almost over and thus the co-infection rates are low. A recent research found moderate to strong correlation between higher influenza vaccine uptake in the elderly and lower COVID-19 deaths in Italy. This might be explained by the prevention of influenza co-infection. In elderly, both influenza and COVID-19 have higher rates of mortality. The impact of prevention of influenza in this fragile group is higher. Current influenza-COVID-19 co-infection reports suggest that co-infection rates are as high as 57% when influenza is circulating. Pending the new waves of COVID-19, it is reasonable to recommend influenza vaccination especially for elderly, but most probably, to general population. This article is protected by copyright. All rights reserved.

positive: Emerging respiratory infections threatening public health in the Asia‐Pacific region: A position paper of the Asian Pacific Society of Respirology In past decades, we have seen several epidemics of respiratory infections from newly emerging viruses, most of which originated in animals. These emerging infections, including severe acute respiratory syndrome coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV) and the pandemic influenza A(H1N1) and avian influenza (AI) viruses, have seriously threatened global health and the economy. In particular, MERS‐CoV and AI A(H7N9) are still causing infections in several areas, and some clustering of cases of A(H5N1) and A(H7N9) may imply future possible pandemics. Additionally, given the inappropriate use of antibiotics and international travel, the spread of carbapenem‐resistant Gram‐negative bacteria is also a significant concern. These infections with epidemic or pandemic potential present a persistent threat to public health and a huge burden on healthcare services in the Asia‐Pacific region. Therefore, to enable efficient infection prevention and control, more effective international surveillance and collaboration systems, in the context of the ‘One Health’ approach, are necessary.

positive: Social distancing measures: evidence of interruption of seasonal influenza activity and early lessons of the SARS-CoV-2 pandemic

positive: Social Distancing against COVID-19: Implication for the Control of Influenza Social distancing has been adopted as one of basic protective measures against coronavirus disease 2019 (COVID-19). During 2019-2020 season, influenza epidemic period was exceptionally short and epidemic peak was low in comparison with previous seasons in Korea. Influenza epidemic pattern was bimodal in 2016-2017 and 2018-2019 seasons, however, influenza viruses have rarely been circulating in spring, 2020 in Korea. Although multiple factors could affect the size of influenza epidemic, extensive application of nonpharmaceutical interventions including mask wearing and social distancing in response to COVID-19 seems to be a major factor of reduced influenza epidemic. Social distancing measures with high feasibility and high acceptability should be implemented even if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are developed in the future. Establishment of guideline for workplace social distancing is needed and it would contribute to reduce disease burden of influenza, especially in vaccine mismatch year.

positive: [Comparison of pathological changes and pathogenic mechanisms caused by H1N1 influenza virus, highly pathogenic H5N1 avian influenza virus, SARS-CoV, MERS-CoV and 2019-nCoV]. 我国武汉出现的新型冠状病毒肺炎疫情经过迅速发展已对全国造成严重影响，但到目前为止对新型冠状病毒肺炎病理变化和发病机制却知之甚少。该文总结重症流感病毒H1N1、高致病性禽流感病毒H5N1、SARS-CoV、MERS-CoV及2019-nCoV几种引起重大疫情病毒感染性疾病的病理改变，尸检肺组织均表现为弥漫性肺泡损伤（diffuse alveolar damage，DAD），但不同病毒引起的病理表现存在差异，重症流感病毒2009 H1N1病毒与受体α-2，6-SA及α-2，3-SA结合，除DAD病变外，常伴有上呼吸道、气管、支气管和细支气管的炎性病变，且较易合并细菌感染。高致病性禽流感病毒H5N1主要结合α-2，3-SA受体，主要累及肺泡上皮及细支气管，少见上呼吸道及气管、支气管病变，常伴局灶肺出血及肺组织坏死，机化及纤维化较少见。SARS-CoV通过结合血管紧张素转换酶2（ACE2）进入细胞，病变与病程相关，DAD渗出期一般见于病程10~14 d死亡患者。病程大于10 d患者表现为DAD机化期，并常伴有闭塞性细支气管炎伴机化性肺炎样改变及肺泡腔内显著多核巨细胞。SARS-CoV及H5N1感染患者肺外器官均可见脾和淋巴结内淋巴细胞耗竭、急性肾小管坏死、骨髓内噬血细胞现象。.

positive: Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19) A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.

positive: What Should Gastroenterologists and Patients Know About COVID-19?

positive: Comparison of Influenza Epidemiological and Virological Characteristics between Outpatients and Inpatients in Zhejiang Province, China, March 2011–June 2015 Given the rapid rate of global spread and consequently healthcare costs related to influenza, surveillance plays an important role in monitoring the emerging pandemics in China. However, the characteristics of influenza in Southeast of China haven’t been fully studied. Our study use the surveillance data collected from 16 sentinel hospitals across Zhejiang Province during March 2011 through June 2015, including the demographic information and respiratory specimens from influenza-like illness (ILI) patients and severe acute respiratory illness (SARI) patients. As analysis results, most SARI and ILI patients were in the age group of 0–4 years old (62.38% of ILI and 71.54% of SARI). The respiratory specimens have statistically significantly higher positive rate for influenza among ILI patients than that among SARI patients (p < 0.001). The comparison between ILI patients and SARI patients shows no statistically significantly difference in detecting influenza virus type and influenza A virus subtype. The SARI and ILI patients were found to be positively correlated for overall positive rate (r = 0.63, p < 0.001), the weekly percentage of A(H1N1)pdm09 (r = 0.51, p < 0.001), influenza B virus (r = 0.17, p = 0.013), and A/H3N2 (r = 0.43, p < 0.001) among all the positive numbers. Our study demonstrated that the activities of influenza virus, including its subtypes, had a similar temporal pattern between ILI and SARI cases.

positive: Eco-epidemiological assessment of the COVID-19 epidemic in China, January–February 2020 Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance as the pandemic develops. Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation. Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25° latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5–7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios. Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single confirmed case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 confirmed cases. Weekly means of maximum daily temperature varied from −28.0°C to 30.1°C, minimum daily temperature from −42.4°C to 23.0°C, maximum solar radiation from 0.04 to 2.74 MJm(−2) and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence. Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.

positive: The calendar of epidemics: Seasonal cycles of infectious diseases

positive: Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2): A global pandemic and treatments strategies The emergence and rapid spread of novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a potentially fatal disease is swiftly evolving public health crises worldwide. The origin of SARS-CoV-2 infection was first reported in people exposed to wet animal market in Wuhan City, China in December 2019. It was suggested that the infection is likely to be of zoonotic origin and transmitted to human through yet unknown intermediary. As of (22/05/2020), there are around 4,995,996 confirmed cases reported by WHO with 327,821 deaths. SARS-CoV-2 infection is transmitted via inhalation or direct contact of infected people's droplets. It has an incubation period ranging from 2 to 14 days or more. The rate of spread of SARS-CoV-2 is more than partially resembled coronavirus (SARS-CoV and MERS). The symptoms are similar to influenza like, breathlessness, sore throat and fatigue therefore, infected person is isolated and administrated with effective treatments. Infection is mild in most but in elderly (>50 years) and those with cardiac and respiratory disorder, it may progress to pneumonia, acute respiratory distress syndrome, and multi organ failure. People with strong immunity or those developed herd immunity are asymptomatic. Fatality rate ranges to 3-4% on case basis. Diagnosis of SARS-CoV-2 is recommended in respiratory secretions by special molecular tests like PCR, chest scan and common laboratory diagnosis. Currently, the existing treatment is essentially supportive and role of antiviral agents is yet to be established as there is no vaccination or therapy available. This review focuses on epidemiology, symptoms, transmission, pathogenesis, ongoing available treatments and future perspectives of SARS-CoV-2.

positive: The COVID-19 Pandemic: Changing Lives and Lessons Learned

positive: Mortality burden from seasonal influenza in Chongqing, China, 2012-2018 Purpose: To estimate influenza-associated excess mortality rates (EMRs) in Chongqing from 2012 to 2018.Methods: We obtained weekly mortality data for all-cause and four underlying causes of death (circulatory and respiratory disease (CRD), pneumonia and influenza (P&I), chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IDH)), and influenza surveillance data, from 2012 to 2018. A negative-binomial regression model was used to estimate influenza-associated EMRs in two age groups (<65 years and ≥65 years).Results: It was estimated that an annual average of 10025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths. The average EMR for all-cause death associated with influenza was 33.5 (95% confidence interval (CI): 31.5-35.6) per 100 000 persons, and in separate cause-specific models we attributed 24.7 (95% CI: 23.3-26.0), 0.8 (95% CI: 0.7-0.8), 8.5 (95% CI: 8.1-9.0) and 5.0 (95% CI: 4.7-5.3) per 100 000 persons EMRs to CRD, P&I, COPD and IDH, respectively. The estimated EMR for influenza B virus was 20.6 (95% CI: 20.3-21.0), which was significantly higher than the rates of 5.3 (95% CI: 4.5-6.1) and 7.5 (95% CI: 6.7-8.3) for A(H3N2) and A(H1N1) pdm09 virus, respectively. The estimated EMR was 152.3 (95% CI: 136.1-168.4) for people aged ≥65 years, which was significantly higher than the rate for those aged <65 years (6.8, 95% CI: 6.3-7.2).Conclusions: Influenza was associated with substantial EMRs in Chongqing, especially among elderly people. Influenza B virus caused a relatively higher excess mortality impact compared with A(H1N1)pdm09 and A(H3N2). It is advisable to optimize future seasonal influenza vaccine reimbursement policy in Chongqing to curb disease burden.

positive: The Coronavirus Pandemic: What Does the Evidence Show? Coronavirus disease 2019 (COVID-19) is a newly emerged disease that has become a global public health concern as it rapidly spread around the world. The etiologic agent responsible for this disease has been named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses as it shows similar genomic features to that of SARS-CoV which caused a pandemic in 2002. This disease first appeared in Hubei province of China and it follows human-to-human transmission but the path this virus took to set up human infection remains a mystery. By 17 April 2020, globally there have been 2,074,529 confirmed cases with 139,378 deaths because of COVID-19. SARS-CoV-2 shows several similarities with SARS?CoV, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) with its clinical presentations. This can vary from asymptomatic infection to severe disease and mortality. Real-time reverse-transcription polymerase chain reaction (rRT-PCR) screening is considered as the standard laboratory test for the diagnosis of COVID-19. There is no proven antiviral agent against SARS-CoV-2 so the treatment for COVID-19 is symptomatic, aiming for the management of the symptoms and prevention of the complications. The outbreak of COVID-19 has led to the implementation of extraordinary public health measures throughout the world. Numerous antiviral compounds used to treat other infections are being clinically researched to find possible treatment. Similarly, the traditional public health outbreak response strategy of isolation, quarantine, social distancing and community containment has been implemented in multiple countries and has played an important role in the prevention of new outbreaks. This review aims to enhance our understanding of COVID 19. Keywords: Coronavirus disease 2019; COVID-19; SARS-CoV-2; novel coronavirus 2019; severe acute respiratory syndrome-2.

positive: Subsequent waves of viral pandemics, a hint for the future course of the SARS-CoV-2 pandemic. Background It is unknown if the SARS-CoV-2 pandemic will have a second wave. We analysed published data of five influenza pandemics (such as the Spanish Flu and the Swine Flu) and the SARS-CoV-1 pandemic to describe whether there were subsequent waves and how they differed. Methods We reanalysed literature and WHO reports on SARS-CoV-1 and literature on five influenza pandemics. We report frequencies of second and third waves, wave heights, wavelengths and time between subsequent waves. From this, we estimated peak-to-peak ratios to compare the wave heights, and wave-length-to-wave-length ratios to compare the wavelengths differences in days. Furthermore, we analysed the seasonality of the wave peaks and the time between the peak values of two waves. Results Second waves, the Spanish Flu excluded, were usually about the same height and length as first waves and were observed in 93% of the 57 described epidemic events of influenza pandemics and in 42% of the 19 epidemic events of the SARS-CoV-1 pandemic. Third waves occurred in 54% of the 28 influenza and in 11% of the 19 SARS-CoV-1 epidemic events. Third waves, the Spanish Flu excluded, usually peaked higher than second waves with a peak-to-peak ratio of 0.5. Conclusion While influenza epidemics are usually accompanied by 2nd waves, this is only the case in the minority of SARS-Cov1 epidemics.

positive: Coronaphobia: Fear and the 2019-nCoV outbreak

positive: Distinguishing between direct and indirect consequences of covid-19.

positive: The COVID-19 pandemic in the USA: what might we expect?

positive: Co-infection of SARS-CoV-2 and Influenza virus in Early Stage of the COVID-19 Epidemic in Wuhan, China • Of the 1001 influenza positive samples, 3 outpatients and 1 inpatient were co-infected with SARS-CoV-2 in Wuhan in January, 2020. • Clinical and laboratory features indicate the 3 outpatients showed mild symptoms, and the inpatient experienced malignant tumor and had worse outcomes from COVID-19. • In January, when the testing capacity is insufficient, co-infection of SARS-CoV-2 with influenza viruses in winter influenza activity peak season may contribute the expansion of SARS-CoV-2 in the local population.

positive: Inequality in acute respiratory infection outcomes in the United States: A review of the literature and its implications for public health policy and practice. Seasonal and pandemic respiratory viruses such as influenza and the novel coronavirus (SARS-COV-2) currently sweeping the globe have often been described as 'equal opportunity infectors', implying little socioeconomic disparity in susceptibility. However, early data from the COVID-19 pandemic has underscored that the burden of respiratory viruses actually reflect and magnify existing socioeconomic inequalities. We review the literature on socioeconomic and racial disparities in acute respiratory infection (ARI), as well as ARI-associated hospitalization and mortality. Our goal is to identify key principles of the relationship between socioeconomic inequality and ARI outcomes, as well as highlighting poorly understood areas that need to be addressed by research and policy in the wake of the COVID-19 pandemic. We find that there has been descriptive work in this area, but that there is a distinct lack of cohesive methodology in the literature exploring social determinants and ARI. We propose the fundamental cause theory is a useful framework for guiding future research of disparities in ARI and for the design of interventions to alleviate these disparities.

positive: N95 Respirators vs Medical Masks for Preventing Influenza Among Health Care Personnel: A Randomized Clinical Trial. Importance Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections. Objective To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP. Design, Setting, and Participants A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups. Interventions Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness. Main Outcomes and Measures The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed. Results Among 2862 randomized participants (mean [SD] age, 43 [11.5] years; 2369 [82.8%]) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, [95% CI, -0.5% to 2.5%]; P = .18) (adjusted odds ratio [OR], 1.18 [95% CI, 0.95-1.45]). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, -21.9 per 1000 HCP-seasons [95% CI, -48.2 to 4.4]; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, -8.9 per 1000 HCP-seasons, [95% CI, -33.3 to 15.4]; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, -8.6 per 1000 HCP-seasons [95% CI, -28.2 to 10.9]; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, -11.3 per 1000 HCP-seasons [95% CI, -23.8 to 1.3]; P = .08). In the respirator group, 89.4% of participants reported "always" or "sometimes" wearing their assigned devices vs 90.2% in the mask group. Conclusions and Relevance Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza. Trial Registration ClinicalTrials.gov Identifier: NCT01249625.

positive: Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 Severe coronavirus disease 2019 (COVID-19) is commonly complicated with coagulopathy, the difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 has not been analyzed. Coagulation results and clinical features of consecutive patients with severe pneumonia induced by SARS-CoV2 (COVID group) and non-SARS-CoV2 (non-COVID group) in Tongji hospital were retrospectively analyzed and compared. Whether patients with elevated D-dimer could benefit from anticoagulant treatment was evaluated. There were 449 COVID patients and 104 non-COVID patients enrolled into the study. The 28-day mortality in COVID group was approximately twofold of mortality in non-COVID group (29.8% vs. 15.4%, P = 0.003), COVID group were older (65.1 ± 12.0 vs. 58.4 ± 18.0, years, P < 0.001) and with higher platelet count (215 ± 100 vs. 188 ± 98, ×10(9)/L, P = 0.015), comparing to non-COVID group. The 28-day mortality of heparin users were lower than nonusers In COVID group with D-dimer > 3.0 μg/mL (32.8% vs. 52.4%, P = 0.017). Patients with severe pneumonia induced by SARS-CoV2 had higher platelet count than those induced by non-SARS-CoV2, and only the former with markedly elevated D-dimer may benefit from anticoagulant treatment.

positive: Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1 BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. RESEARCH QUESTION: The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. STUDY DESIGN AND METHODS: This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. RESULTS: The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao2/Fio2 of 198.5 mm Hg in the COVID-19 cohort was significantly higher than the Pao2/Fio2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). INTERPRETATION: There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

positive: SARS-CoV-2 detection in patients with influenza-like illness. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei Province, China in late December 2019. We re-analysed 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020 and found that 9 of the 640 throat swabs were positive for SARS-CoV-2 RNA by quantitative PCR, suggesting community transmission of SARS-CoV2 in Wuhan in early January 2020.

positive: Climatic influences on the worldwide spread of SARS-CoV-2 The rapid global spread of the novel, pathogenic, SARS-CoV-2 causing the severe acute respiratory disease COVID-19, becomes a major health problem worldwide and pose the need for international predictive programs. Given the lack of both specific drugs and an efficient preventive vaccine, the expectation that SARS-CoV-2 transmission rate might decrease in temperate regions during summer, dominated the social scene. Here, we attempted a prediction of the worldwide spread of the infections based on climatic data, expressed by 19 bioclimatic variables. The calculated probability maps shown that potential areas of infection follow a shift from the Tropical to Temperate and Mediterranean Bioclimatic regions, and back to the Tropics again. Maps show an increased probability of infections in Europe, followed by an expansion covering areas of the Middle East and Northern Africa, as well as Eastern coastal areas of North America, South-Eastern coastal areas of Latin America and two areas of Southern Australia, and later return to areas of Southeastern Asia, in a manner similar to that of influenza strains (H3N2). Our approach may therefore be of value for the worldwide spread of SARS-CoV-2, suggesting an optimistic scenario of asynchronous seasonal global outbreaks, like other viral respiratory diseases. Consequently, we suggest the incorporation of a climatic impact in the design and implementation of public health policies. Maps of our model are available (constantly updated up to the saturation of the model) at: https://navaak.shinyapps.io/CVRisk/.

positive: Differentiating between 2019 novel coronavirus pneumonia and influenza using a non-specific laboratory marker-based dynamic nomogram BACKGROUND: There is currently a lack of non-specific laboratory indicators as a quantitative standard to distinguish between the 2019 coronavirus disease (COVID-19) and an influenza A or B virus infection. Thus, the aim of this study was to establish a nomogram to detect COVID-19. METHODS: A nomogram was established using data collected from 457 patients (181 with COVID-19 and 276 with influenza A or B infection) at China. The nomogram used age, lymphocyte percentage, and monocyte count to differentiate COVID-19 from influenza. RESULTS: Our nomogram predicted probabilities of COVID-19 with an AUROC of 0.913 (95% confidence interval [CI], 0.883–0.937), greater than that of the lymphocyte-to-monocyte ratio (0.849, 95%CI, 0.812–0.880; p = 0.0007), lymphocyte percentage (0.808, 95%CI, 0.768–0.843; p < 0.0001), monocyte count (0.780, 95%CI, 0.739–0.817; p < 0.0001), or age (0.656, 95%CI, 0.610–0.699; p < 0.0001). The predicted probability conformed to the real observation outcomes of COVID-19, according to the calibration curves. CONCLUSIONS: We found that age, lymphocyte percentage, and monocyte count are risk factors for the early-stage prediction of patients infected with the 2019 novel coronavirus. As such, our research provides a useful test for doctors to differentiate COVID-19 from influenza.

positive: Symptom-Based Isolation Policies: Evidence from a Mathematical Model of Outbreaks of Influenza and COVID-19 BACKGROUND: Controlling the transmission of respiratory infections such as influenza and COVID-19 is a critical public health priority. Non-pharmaceutical intervention policies such as community quarantines, closures and travel bans are often implemented in emergencies but many of them are disruptive and difficult to maintain for extended periods of time. A promising alternative recommended by the CDC for influenza is requiring individuals showing fever symptoms to remain isolated at home until they are fever-free for at least one day, but there is limited evidence to support the effectiveness of such symptom-based isolation policies. METHODS: Here we introduce a computational model of symptom-based isolation that accounts for the timing of symptoms, viral shedding and the population structure. It was validated on outbreaks of influenza in schools and modified to account for COVID-19. It was then used to estimate the outbreak curves and the attack rates (the proportion of the population infected) under one or more days of fever-based isolation. RESULTS: Using the model we find evidence that symptom-based isolation policies could reduce the attack rates of both influenza and COVID-19 outbreaks, and flatten the outbreak curves. Specifically, we found that across a range of influenza scenarios, a CDC-recommended policy of one day isolation following fever can reduce the attack rate from 27% of the population to 12%, and to 3% if the isolation is extended to two days. In COVID-19 transmission, we estimate that implementing one day post-fever isolation would reduce the attack rate from 79% to 71%, and there is possible benefit from isolation for six days. In both influenza and COVID-19, the policies are predicted to reduce the peak number of infected but not shorten the outbreak duration. CONCLUSIONS: Symptom-based isolation could be an important tool to control influenza and COVID-19 outbreaks in schools, and potentially other settings. We recommend that schools implement a post-fever isolation policy of two days for influenza and six days for COVID-19.

positive: [Comparison of pathological changes and pathogenic mechanisms caused by H1N1 influenza virus, highly pathogenic H5N1 avian influenza virus, SARS-CoV, MERS-CoV and 2019-nCoV]

positive: Influenza, respiratory syncytial virus and SARS Abstract Acute lower respiratory tract infections (LRTIs) are a major worldwide health problem, particularly in childhood. About 30–50% of acute LRTIs are viral in origin; of these, influenza and respiratory syncytial virus are associated with the greatest disease burden in humans. Many different influenza A viruses occur naturally in animal reservoirs, and present a constant threat of zoonotic infections and global pandemics. The pandemic (H1N1) influenza virus that emerged in humans in 2009 contained a unique combination of genes originating in swine and the global human population was highly susceptible to the novel strain. The emergence of the severe acute respiratory syndrome coronavirus in 2003, and the ensuing worldwide epidemic, highlights the fact that respiratory viral infections in humans may originate in animals. Preventative measures for influenza include annual vaccination and treatment with antiviral drugs such as the neuraminidase inhibitors oseltamivir and zanamivir. Subtype-dependent resistance to antivirals can develop and should be closely monitored.

positive: NKG2A and COVID-19: another brick in the wall

positive: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0–16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.

positive: On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic BACKGROUND: It has been observed that, historically, strains of pandemic influenza led to succeeding seasonal waves, albeit with decidedly different patterns. Recent studies suggest that the 2009 A(H1N1)pdm09 pandemic has had an impact on the circulation patterns of seasonal influenza strains in the post-pandemic years. In this work we aim to investigate this issue and also to compare the relative transmissibility of these waves of differing strains using Taiwan influenza surveillance data before, during and after the pandemic. METHODS: We make use of the Taiwan Center for Disease Control and Prevention influenza surveillance data on laboratory-confirmed subtyping of samples and a mathematical model to determine the waves of circulating (and co-circulating) H1, H3 and B virus strains in Taiwan during 2008–2014; or namely, short before, during and after the 2009 pandemic. We further pinpoint the turning points and relative transmissibility of each wave, in order to ascertain whether any temporal pattern exists. RESULTS/FINDINGS: For two consecutive years following the 2009 pandemic, A(H1N1)pdm09 circulated in Taiwan (as in most of Northern Hemisphere), sometimes co-circulating with AH3. From the evolution point of view, A(H1N1)pdm09 and AH3 were able to sustain their circulation patterns to the end of 2010. In fact, A(H1N1)pdm09 virus circulated in six separate waves in Taiwan between summer of 2009 and spring of 2014. Since 2009, a wave of A(H1N1)pmd09 occurred every fall/winter influenza season during our study period except 2011–2012 season, when mainly influenza strain B circulated. In comparing transmissibility, while the estimated per capita weekly growth rates for cumulative case numbers (and the reproduction number) seem to be lower for most of the influenza B waves (0.06~0.26; range of 95% CIs: 0.05~0.32) when compared to those of influenza A, the wave of influenza B from week 8 to week 38 of 2010 immediately following the fall/winter wave of 2009 A(H1N1) pdm09 was substantially higher at r = 0.89 (95% CI: 0.49, 1.28), in fact highest among all the waves detected in this study. Moreover, when AH3 or A(H1N1)pdm09 exhibit high incidence, reported cases of subtype B decreases and vice versa. Further modeling analysis indicated that during the study period, Taiwan nearly experienced at least one wave of influenza epidemic of some strain every summer except in 2012. DISCUSSION: Estimates of R for seasonal influenza are consistent with that of temperate and tropical-subtropical regions, while estimate of R for A(H1N1)pdm09 is comparatively less than countries in Europe and North America, but similar to that of tropical-subtropical regions. This offers indication of regional differences in transmissibility of influenza virus that exists only for pandemic influenza. Despite obvious limitations in the data used, this study, designed to qualitatively compare the temporal patterns and transmissibility of the waves of different strains, illustrates how influenza subtyping data can be utilized to explore the mechanism for various influenza strains to compete or to circulate, to possibly provide predictors of future trends in the evolution of influenza viruses of various subtypes, and perhaps more importantly, to be of use to future annual seasonal influenza vaccine design.

positive: Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus On 15 April and 17 April 2009, novel swineorigin influenza A (H1N1) virus was identifi ed in specimens obtained from two epidemiologically unlinked patients in the United States. The ongoing outbreak of novel H1N1 2009 influenza (swine influenza) has caused more than 3,99,232 laboratory confi rmed cases of pandemic influenza H1N1 and over 4735 deaths globally. This novel 2009 influenza virus designated as H1N1 A/swine/California/04/2009 virus is not zoonotic swine flu and is transmitted from person to person and has higher transmissibility then that of seasonal influenza viruses. In India the novel H1N1 virus infection has been reported from all over the country. A total of 68,919 samples from clinically suspected persons have been tested for influenza A H1N1 across the country and 13,330 (18.9%) of them have been found positive with 427 deaths. At the All India Institute of Medical Sciences, New Delhi India, we tested 1096 clinical samples for the presence of novel H1N1 influenza virus and seasonal influenza viruses. Of these 1096 samples, 194 samples (17.7%) were positive for novel H1N1 influenza virus and 197 samples (18%) were positive for seasonal influenza viruses. During outbreaks of emerging infectious diseases accurate and rapid diagnosis is critical for minimizing further spread through timely implementation of appropriate vaccines and antiviral treatment. Since the symptoms of novel H1N1 influenza infection are not specifi c, laboratory confi rmation of suspected cases is of prime importance.

positive: Recent advances in influenza vaccines Seasonal influenza remains a major public health problem, responsible for hundreds of thousands of deaths every year, mostly of elderly people. Despite the wide availability of vaccines, there are multiple problems decreasing the effectiveness of vaccination programs. These include viral variability and hence the requirement to match strains by estimating which will become prevalent each season, problems associated with vaccine and adjuvant production, and the route of administration as well as the perceived lower vaccine efficiency in older adults. Clinical protection is still suboptimal for all of these reasons, and vaccine uptake remains too low in most countries. Efforts to improve the effectiveness of influenza vaccines include developing universal vaccines independent of the circulating strains in any particular season and stimulating cellular as well as humoral responses, especially in the elderly. This commentary assesses progress over the last 3 years towards achieving these aims. Since the beginning of 2020, an unprecedented international academic and industrial effort to develop effective vaccines against the new coronavirus SARS-CoV-2 has diverted attention away from influenza, but many of the lessons learned for the one will synergize with the other to mutual advantage. And, unlike the SARS-1 epidemic and, we hope, the SARS-CoV-2 pandemic, influenza will not be eliminated and thus efforts to improve influenza vaccines will remain of crucial importance.

positive: Modeling the impact of mass influenza vaccination and public health interventions on COVID-19 epidemics with limited detection capability The emerging coronavirus SARS-CoV-2 has caused a COVID-19 pandemic. SARS-CoV-2 causes a generally mild, but sometimes severe and even life-threatening infection, known as COVID-19. Currently, there exist no effective vaccines or drugs and, as such, global public authorities have so far relied upon non pharmaceutical interventions (NPIs). Since COVID-19 symptoms are aspecific and may resemble a common cold, if it should come back with a seasonal pattern and coincide with the influenza season, this would be particularly challenging, overwhelming and straining the healthcare systems, particularly in resource-limited contexts, and would increase the likelihood of nosocomial transmission. In the present study, we devised a mathematical model focusing on the treatment of people complaining of influenza-like-illness (ILI) symptoms, potentially at risk of contracting COVID-19 or other emerging/re-emerging respiratory infectious agents during their admission at the health-care setting, who will occupy the detection kits causing a severe shortage of testing resources. The model is used to assess the effect of mass influenza vaccination on the spread of COVID-19 and other respiratory pathogens in the case of a coincidence of the outbreak with the influenza season. Here, we show that increasing influenza vaccine uptake or enhancing the public health interventions would facilitate the management of respiratory outbreaks coinciding with the peak flu season, especially, compensate the shortage of the detection resources. However, how to increase influenza vaccination coverage rate remains challenging. Public health decision- and policy-makers should adopt evidence-informed strategies to improve influenza vaccine uptake.

positive: Understanding dynamics of pandemics Along the centuries, novel strain of virus such as influenza produces pandemics which increase illness, death and disruption in the countries. Spanish flu in 1918, Asian flu in 1957, Hong Kong flu in 1968 and swine flu in 2009 were known pandemic which had various characteristics in terms of morbidity and mortality. A current pandemic is caused by novel corona virus originated from China. COVID-19 pandemic is very similar to Spanish, Hong Kong, Asian and swine influenza pandemics in terms of spreading to world by the mobilized people. Burden of pandemic is considered in terms of disease transmissibility and the growth rate of epidemic and duration of pandemic can be calculated by transmissibility characteristic. The case definition, finding out cases and first case cluster, proper treatment, sufficient stockpiles of medicine and population cooperation with the containment strategy should be considered for reduction of burden of pandemic.

positive: Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing BACKGROUND: Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed the characteristics of different respiratory viral infections. METHODS: Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in a fever clinic. RESULTS: Overall, 1860 patients were screened, and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infections, respectively. The COVID-19 group had a higher rate of contact with the epidemic area within 14 days and of clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever to the highest temperature was higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had a lower white blood cell count and neutrophil count than Flu A virus and RSV infection groups, but higher lymphocyte count than Flu A and B virus infection groups. The COVID-19 group (83.33%) had a higher rate of pneumonia in chest CT scans than Flu A and B virus infection groups. CONCLUSIONS: Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of a specific respiratory virus; however, epidemic history was significant for the screening of COVID-19.

positive: [Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia] The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.

positive: Does this patient have COVID-19? A practical guide for the internist Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its 'semeiotic'. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.

positive: The social politics of pandemic influenzas: the question of (permeable) international, inter-species, and interpersonal boundaries Purpose – This chapter considers the social politics of H5N1 (“avian influenza”), the 2009 H1N1 pandemic, and the response to it within the context of the history of pandemic influenzas and the continuing need for robust preventative public health systems more generally. In particular, the author considers how the borders between nations, species, and individuals are thrown into relief and called into question by influenza outbreaks and their management. Methodology/approach – This work relies on literature review, media research, and critical and interpretative sociological methods. Findings – While panic surrounding new and potentially highly virulent influenza strains is reasonable, such panic is not sustainable and belies the fact that every year presents the danger of a pandemic. This chapter argues that, if public health systems only respond to immediate panic and fail to consider how quickly airborne diseases can cross all sorts of borders, they do not attend to the real need for far-seeing, long-term, internationally collaborative disease prevention and disaster preparedness. Contribution to the field – The author offers a critical and wellness- and prevention-oriented perspective on what priorities should be emphasized in the rapidly growing fields of disaster studies and disaster preparedness, which, by their nature, tend to be crisis oriented and focused on the micro-term, with planning done on a case-by-case basis. Such a narrow focus can render preventative health systems inflexible and unable to rise to the challenge of a disease that can spread easily through casual contact.

positive: Influenza Influenza continues to baffle humans by its constantly changing nature. The twenty-first century has witnessed considerable advances in the understanding of the influenza viral pathogenesis, its synergy with bacterial infections and diagnostic methods. However, challenges continue: to find a less expensive and more reliable point-of-care test for use in developing countries, to produce more efficacious antiviral drugs, to explore ways to combat emerging antiviral resistance and to develop vaccines that can either be produced in a shorter production time or can overcome the need for annual matching with the circulating influenza strains. Most importantly for India, as a nation that suffered the highest mortality in the influenza pandemic 1918, there is an urgent need to gear up our existing preparedness for the next pandemic which is capable to hit at any moment in time.

positive: Assessing the interactions between COVID-19 and influenza in the United States The 2019–2020 influenza sentinel surveillance data exhibits unexpected trends. Typical influenza seasons have a small herald wave, followed by a decrease due to school closure during holidays, and then a main post-holiday peak that is significantly larger than the pre-holiday wave. During the 2019–2020 influenza season, influenza-like illness data in the United States appears to have a markedly lower main epidemic peak compared to what would be expected based on the pre-holiday peak. We hypothesize that the 2019–2020 influenza season does have a lower than expected burden and that this deflation is due to a behavioral or ecological interaction with COVID-19. We apply an intervention analysis to assess if this influenza season deviates from expectations, then we compare multiple hypothesized drivers of the decrease in influenza in a spatiotemporal regression model. Lastly, we develop a mechanistic metapopulation model, incorporating transmission reduction that scales with COVID-19 risk perception. We find that the 2019–2020 ILI season is smaller and decreases earlier than expected based on prior influenza seasons, and that the increase in COVID-19 risk perception is associated with this decrease. Additionally, we find that a 5% average reduction in transmission is sufficient to reproduce the observed flu dynamics. We propose that precautionary behaviors driven by COVID-19 risk perception or increased isolation driven by undetected COVID-19 spread dampened the influenza season. We suggest that when surveillance for a novel pathogen is limited, surveillance streams of co-circulating infections may provide a signal.

positive: Sustainability of Coronavirus on different surfaces Abstract COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.

positive: Impact of Public Health Interventions on Seasonal Influenza Activity During the SARS-CoV-2 Outbreak in Korea BACKGROUND: COVID-19 was introduced in Korea early and experienced a large outbreak in mid-February. We aimed to review the public health interventions used during the COVID-19 outbreak and describe the impact on seasonal influenza activity in Korea. METHODS: National response strategies and public health interventions, along with daily COVID-19 confirmed cases in Korea were reviewed during the pandemic. National influenza surveillance data were compared between seven sequential seasons. Characteristics of each season, including the rate of influenza-like illness (ILI), duration of epidemic, date of termination of epidemic, distribution of influenza virus strain and hospitalization were analyzed. RESULTS: After various public health interventions including enforced public education on hand hygiene, cough etiquette and staying at home with respiratory symptoms, universal mask use in public places, refrain from non-essential social activities and school closure, the duration of the influenza epidemic in 2019/2020 decreased by 6-12 weeks and the influenza activity peak rated 49.8 ILI/1,000 visits compared to 71.9-86.2 ILI/1,000 visits of previous seasons. During the period of enforced social distancing from week 9 to 17 of 2020, influenza hospitalization cases were 11.9-26.9-fold lower compared with previous seasons. During the 2019/2020 season, influenza B accounted for only 4%, in contrast with previous seasons in which influenza B accounted for 26.6% to 54.9% of all cases. CONCLUSIONS: Efforts to activate high level national response not only led to a decrease in COVID-19, but also substantial decrease in seasonal influenza activity. Interventions applied to control COVID-19 may serve as useful strategies for prevention and control of influenza in upcoming seasons.

positive: Forecasting the 2017/2018 seasonal influenza epidemic in England using multiple dynamic transmission models: a case study BACKGROUND: Since the 2009 A/H1N1 pandemic, Public Health England have developed a suite of real-time statistical models utilising enhanced pandemic surveillance data to nowcast and forecast a future pandemic. Their ability to track seasonal influenza and predict heightened winter healthcare burden in the light of high activity in Australia in 2017 was untested. METHODS: Four transmission models were used in forecasting the 2017/2018 seasonal influenza epidemic in England: a stratified primary care model using daily, region-specific, counts and virological swab positivity of influenza-like illness consultations in general practice (GP); a strain-specific (SS) model using weekly, national GP ILI and virological data; an intensive care model (ICU) using reports of ICU influenza admissions; and a synthesis model that included all data sources. For the first 12 weeks of 2018, each model was applied to the latest data to provide estimates of epidemic parameters and short-term influenza forecasts. The added value of pre-season population susceptibility data was explored. RESULTS: The combined results provided valuable nowcasts of the state of the epidemic. Short-term predictions of burden on primary and secondary health services were initially highly variable before reaching consensus beyond the observed peaks in activity between weeks 3–4 of 2018. Estimates for R(0) were consistent over time for three of the four models until week 12 of 2018, and there was consistency in the estimation of R(0) across the SPC and SS models, and in the ICU attack rates estimated by the ICU and the synthesis model. Estimation and predictions varied according to the assumed levels of pre-season immunity. CONCLUSIONS: This exercise successfully applied a range of pandemic models to seasonal influenza. Forecasting early in the season remains challenging but represents a crucially important activity to inform planning. Improved knowledge of pre-existing levels of immunity would be valuable.

positive: Focus on Mental Health During the Coronavirus (COVID-19) Pandemic: Applying Learnings from the Past Outbreaks The 2019 novel coronavirus (COVID-19) has gained global attention after it originated from China at the end of 2019, and later turned into pandemic as it affected about 118,000 in 114 countries by March 11, 2020. By March 13, 2020, it was declared a national emergency in the United States as the number of COVID-19 cases, and the death toll rose exponentially. To contain the spread of the disease, the world scientist community came together. However, the unpreparedness of the nations, even with the advanced medical sciences and resources, has failed to address the mental health aspect amongst the public, as all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of COVID-19 pneumonia. Our efforts in this review are to evaluate and study similar outbreaks from the past to understand its adverse impact on mental health, implement adequate steps to tackle and provide a background to physicians and healthcare workers at the time of such outbreaks to apply psychological first aid.

positive: Can an effective SARS-CoV-2 vaccine be developed for the older population? The emergence of SARS-CoV-2 and its inordinately rapid spread is posing severe challenges to the wellbeing of millions of people worldwide, health care systems and the global economy. While many younger people experience no or mild symptoms on infection, older adults are highly susceptible to life-threatening respiratory and systemic conditions which demand a full understanding and leveraging of knowledge of the differences between immunity in young and old people. Consequently, we welcome papers addressing any issues relevant to immunity and ageing in the context of SARS-CoV-2, and will endeavour to fast-track peer-review. We aim to provide a platform exclusively for discussions of individual and age differences in susceptibility and immune responses to COVID caused by SARS-CoV-2 infection and how to prevent or reduce severity of disease in older adults.

positive: The Relationship between the Global Burden of Influenza from 2017-2019 and COVID-19 Background SARS-CoV-2 and Influenza are lipid-enveloped viruses with differential morbidity and mortality but shared modes of transmission. We assessed whether historical patterns of regional influenza burden are reflected in the observed heterogeneity in COVID-19 cases across and within regions of the world. Methods Weekly surveillance data reported in FluNet from January 2017-December 2019 for influenza and World Health Organization for COVID-19 (to May 31, 2020) across the seven World Bank regions were used to assess the total and annual number of influenza and COVID-19 cases per country, within and across all regions, to generate comparative descending ranks from highest to lowest burden of disease. Results Across and within regions, rankings of influenza and COVID-19 were relatively consistent. Europe and Central Asia and North America ranked first and second for COVID-19 and second and first for influenza, respectively. East Asia and the Pacific traditionally ranked higher for influenza but to date, has been less affected by COVID-19. Between regions, Sub-Saharan Africa ranked amongst the least affected by both influenza and COVID-19. Conclusion Consistency in distribution of the burden of COVID-19 and influenza suggest shared individual, structural, and environmental determinants of transmission. Regions with discrepancies between influenza and COVID-19 burden may provide further insight into the potential impact of non-pharmacologic interventions and intersections with environmental conditions. Ultimately, forecasting trends and informing interventions for novel respiratory pathogens like COVID-19 should leverage patterns in the relative burden of past respiratory pathogens and the relative impact of non-pharmacologic intervention strategies as prior information.

positive: Severity and outcomes of influenza-related pneumonia in type A and B strains in China, 2013–2019 BACKGROUND: Inconsistencies exist regarding the severity of illness caused by different influenza strains. The aim of this study was to compare the clinical outcomes of hospitalized adults and adolescents with influenza-related pneumonia (Flu-p) from type A and type B strains in China. METHODS: We retrospectively reviewed data from Flu-p patients in five hospitals in China from January 2013 to May 2019. Multivariate logistic and Cox regression models were used to assess the effects of influenza virus subtypes on clinical outcomes, and to explore the risk factors of 30-day mortality for Flu-p patients. RESULTS: In total, 963 laboratory-confirmed influenza A-related pneumonia (FluA-p) and 386 influenza B-related pneumonia (FluB-p) patients were included. Upon adjustment for confounders, multivariate logistic regression models showed that FluA-p was associated with an increased risk of invasive ventilation (adjusted odds ratio [aOR]: 3.824, 95% confidence interval [CI]: 2.279–6.414; P < 0.001), admittance to intensive care unit (aOR: 1.630, 95% CI: 1.074–2.473, P = 0.022) and 30-day mortality (aOR: 2.427, 95% CI: 1.568–3.756, P < 0.001) compared to FluB-p. Multivariate Cox regression models confirmed that influenza A virus infection (hazard ratio: 2.637, 95% CI: 1.134–6.131, P = 0.024) was an independent predictor for 30-day mortality in Flu-p patients. CONCLUSIONS: The severity of illness and clinical outcomes of FluA-p patients are more severe than FluB-p. This highlights the importance of identifying the virus strain during the management of severe influenza.

positive: Diagnosing COVID-19: Did We Miss Anything? In late 2019, a mass of patients showing symptoms of a pneumonia-like disease of unknown origin emerged in Wuhan, China. Little did the world know it was the prelude of what would be a devastating pandemic. Samples were collected from these patients and the use of unbiased sequencing, and subsequent isolation of the pathogen using human airway epithelial cells led to the discovery of a novel coronavirus, named 2019-nCoV by the World Health Organization (WHO) and Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The disease caused by this virus is officially called the coronavirus disease 2019 (COVID-19).

positive: Initial success in the identification and management of the coronavirus disease 2019 (COVID-19) indicates human-to-human transmission in Wuhan, China Coronavirus (CoV) has been one of the major pandemic threats to human health in the last two decades. The human coronavirus was first identified in 1960s. CoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV have caused numerous disasters or human deaths worldwide. Recently, an outbreak of the previously unknown deadly CoV disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome CoV 2 (SARS-CoV-2, early named 2019-nCoV) occurred in Wuhan, China, and it had caused 81238 cases of confirmed infection, including 3250 deaths until March 19, 2020. Its risks and pandemic potential have brought global consideration. We summarized epidemiology, virological characteristics, clinical symptoms, diagnostic methods, clinical treatments, and prevention methods for COVID-19 to present a reference for the future wave of probable CoV outbreaks.

positive: The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2â114â269 people, resulting in 145â144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

positive: Coronavirus: Update Related to the Current Outbreak of COVID-19. In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection.

positive: Are children less susceptible to COVID-19?

positive: Meteorological factors and domestic new cases of coronavirus disease (COVID-19) in nine Asian cities: A time-series analysis AIM To investigate the associations of meteorological factors and the daily new cases of coronavirus disease (COVID-19) in nine Asian cities. METHOD Pearson correlation and generalized additive modeling were performed to assess the relationships between daily new COVID-19 cases and meteorological factors (daily average temperature and relative humidity) with the most updated data currently available. RESULTS The Pearson correlation showed that daily new confirmed cases of COVID-19 were more correlated with the average temperature than with relative humidity. Daily new confirmed cases were negatively correlated with the average temperature in Beijing (r=-0.565, P<0.01), Shanghai (r=-0.471, P<0.01), and Guangzhou (r=-0.530, P<0.01) , yet in contrast, positively correlated with that in Japan (r=0.441, P<0.01). In most of the cities (Shanghai, Guangzhou, Hong Kong, Seoul, Tokyo, and Kuala Lumpur), generalized additive modeling analysis showed the number of daily new confirmed cases was positively associated with both average temperature and relative humidity, especially in lagged 3d model, where a positive influence of temperature on the daily new confirmed cases was discerned in 5 cities except in Beijing, Wuhan, Korea, and Malaysia. Nevertheless, the results were inconsistent across cities and lagged time, suggesting meteorological factors were unlikely to greatly influence the COVID-19 epidemic. CONCLUSION The associations between meteorological factors and the number of COVID-19 daily cases are inconsistent across cities and lagged time. Large-scale public health measures and expanded regional research are still required until a vaccine becomes available and herd immunity is established.

positive: Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to sweep the world, causing infection of millions and death of hundreds of thousands. The respiratory disease that it caused, COVID-19 (stands for coronavirus disease in 2019), has similar clinical symptoms with other two CoV diseases, severe acute respiratory syndrome and Middle East respiratory syndrome (SARS and MERS), of which causative viruses are SARS-CoV and MERS-CoV, respectively. These three CoVs resulting diseases also share many clinical symptoms with other respiratory diseases caused by influenza A viruses (IAVs). Since both CoVs and IAVs are general pathogens responsible for seasonal cold, in the next few months, during the changing of seasons, clinicians and public heath may have to distinguish COVID-19 pneumonia from other kinds of viral pneumonia. This is a discussion and comparison of the virus structures, transmission characteristics, clinical symptoms, diagnosis, pathological changes, treatment and prevention of the two kinds of viruses, CoVs and IAVs. It hopes to provide information for practitioners in the medical field during the epidemic season.

positive: Estimating and Projecting Air Passenger Traffic during the COVID-19 Coronavirus Outbreak and its Socio-Economic Impact Abstract Due to the coronavirus global crisis, most countries have put in place restrictive measures in order to confine the pandemia and contain the number of casualties. Among the restrictive measures, air traffic suspension is certainly quite effective in reducing the mobility on the global scale in the short term but it also has high socio-economic impact on the long and short term. The main focus of this study is to collect and prepare data on air passengers traffic worldwide with the scope of analyze the impact of travel ban on the aviation sector. Based on historical data from January 2010 till October 2019, a forecasting model is implemented in order to set a reference baseline. Making use of airplane movements extracted from online flight tracking platforms and on-line booking systems, this study presents also a first assessment of recent changes in flight activity around the world as a result of the COVID-19 pandemic. To study the effects of air travel ban on aviation and in turn its socio-economic, several scenarios are constructed based on past pandemic crisis and the observed flight volumes. It turns out that, according to these hypothetical scenarios, in the first Quarter of 2020 the impact of aviation losses could have negatively reduced World GDP by 0.02% to 0.12% according to the observed data and, in the worst case scenarios, at the end of 2020 the loss could be as high as 1.41-1.67% and job losses may reach the value of 25-30 millions. Focusing on EU27, the GDP loss may amount to 1.66-1.98% by the end of 2020 and the number of job losses from 4.2 to 5 millions in the worst case scenarios. Some countries will be more affected than others in the short run and most European airlines companies will suffer from the travel ban. We hope that that these preliminary results may be of help for informed policy making design of exit strategies from this global crisis.

positive: Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan BACKGROUND: As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults from 2010 to 2018. METHODS: Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. RESULTS: In total, 993 HCoV infections were identified during the 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range, 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. CONCLUSIONS: Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.

positive: Distinguishing COVID-19 from influenza pneumonia in the early stage through CT imaging and clinical features Purpose: To identify differences in CT imaging and clinical features between COVID-19 and influenza pneumonia in the early stage, and to identify the most valuable features in the differential diagnosis. Materials and Method: A consecutive cohort of 73 COVID-19 and 48 influenza pneumonia patients were retrospectively recruited from five independent institutions. The courses of both diseases were confirmed to be in the early stages (mean 2.66 (SD 2.62) days for COVID-19 and mean 2.19 (SD 2.10) days for influenza pneumonia after onset). The chi-square test, student`s t-test, and Kruskal-Wallis H-test were performed to compare CT imaging and clinical features between the two groups. Spearman or Kendall correlation tests between feature metrics and diagnosis outcomes were also assessed. The diagnostic performance of each feature in differentiating COVID-19 from influenza pneumonia was evaluated with univariate analysis. The corresponding area under the curve (AUC), accuracy, specificity, sensitivity and threshold were reported. Results: The ground-glass opacification (GGO) was the most common imaging feature in COVID-19, including pure-GGO (75.3%) and mixed-GGO (78.1%), mainly in peripheral distribution. For clinical features, most COVID-19 patients presented normal white blood cell (WBC) count (89.04%) and neutrophil count (84.93%). Twenty imaging features and 6 clinical features were identified to be significantly different between the two diseases. The diagnosis outcomes correlated significantly with the WBC count (r=-0.526, P<0.001) and neutrophil count (r=-0.500, P<0.001). Four CT imaging features had absolute correlations coefficients higher than 0.300 (P<0.001), including crazy-paving pattern, mixed-GGO in peripheral area, pleural effusions, and consolidation. Conclusions: Among a total of 1537 lesions and 62 imaging and clinical features, 26 features were demonstrated to be significantly different between COVID-19 and influenza pneumonia. The crazy-paving pattern was recognized as the most powerful imaging feature for the differential diagnosis in the early stage, while WBC count yielded the highest diagnostic efficacy in clinical manifestations.

positive: Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes Background. The threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. PubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.

positive: Type I and III interferons disrupt lung epithelial repair during recovery from viral infection Excessive cytokine signalling frequently exacerbates lung tissue damage during respiratory viral infection. Type I and III interferons (IFN-α/β and IFN-λ) are host-produced antiviral cytokines and currently considered as COVID-19 therapy. Prolonged IFN-α/β responses can lead to harmful proinflammatory effects, whereas IFN-λ mainly signals in epithelia, inducing localised antiviral immunity. Here we show that IFN signalling interferes with lung repair during influenza recovery, with IFN-λ driving these effects most potently. IFN-induced p53 directly reduces epithelial proliferation and differentiation, increasing disease severity and susceptibility to bacterial superinfections. Hence, excessive or prolonged IFN-production aggravates viral infection by impairing lung epithelial regeneration. Therefore, timing and duration are critical parameters of endogenous IFN action, and should be considered carefully for IFN therapeutic strategies against viral infections like influenza and COVID-19. One Sentence Summary A novel IFN-mediated mechanism of immunopathology during respiratory virus infection by interference with lung tissue repair.

positive: Identifying potential undocumented COVID-19 using publicly reported influenza-like-illness and laboratory-confirmed influenza disease in the United States: An approach to syndromic surveillance? In the absence of widespread testing, syndromic surveillance approaches may be useful for understanding potential undocumented coronavirus disease 2019 (COVID-19) in the United States. We used publicly available data from the Centers for Disease Control and Prevention FluView Interactive to evaluate its potential for COVID-19 syndromic surveillance. Unlike the prior 3 influenza seasons, we found a 76% decrease in influenza positive tests and a 27% increase in influenza like illness during the weeks since COVID-19 outbreaks began in the United States, which suggests FluView's potential utility for COVID-19 syndromic surveillance.

positive: Counting the cost of COVID-19 Coronavirus disease 2019 (COVID-19) is the name given by the World Health Organization (WHO) to the highly contagious and infectious disease caused by the Novel Corona Virus or SARS-CoV-2, which was first reported on 31 December 2019 in Wuhan city of the capital of China's Hubei province. Due to the rapid increase in the number of infections worldwide, the WHO in March 2020, declared COVID-19 as a pandemic. Historically, first coronavirus had surfaced in 1965 with symptoms of common cold. Since then five different strands of this virus have emerged, most lethal of them was the Severe Acute Respiratory Syndrome (SARS), which infected about eight thousand people, killing ten percent of them. The COVID-19 is not the most deadly pandemic world has ever witnessed as the Spanish influenza pandemic, during 1918–19, killed more than fifty million people. Indeed COVID-19 has turned out to be the most lethal of all coronaviruses as it has infected at least three million people killing more than two hundred thousands of them in the first 4 months of its spread. Many politicians and social scientists have dubbed the depression, being caused by COVID-19, worse than that caused by the Second World War. In this article, we shall analyze economic, social, cultural, educational and political impact of the COVID-19.

positive: Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic.

positive: Genetic analysis of the novel SARS-CoV-2 host receptor TMPRSS2 in different populations The infection coronavirus disease 2019 (COVID-19) is caused by a virus classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At cellular level, virus infection initiates with binding of viral particles to the host surface cellular receptor angiotensin converting enzyme 2 (ACE2). SARS-CoV-2 engages ACE2 as the entry receptor and employs the cellular serine protease 2 (TMPRSS2) for S protein priming. TMPRSS2 activity is essential for viral spread and pathogenesis in the infected host. Understanding how TMPRSS2 protein expression in the lung varies in the population could reveal important insights into differential susceptibility to influenza and coronavirus infections. Here, we systematically analyzed coding-region variants in TMPRSS2 and the eQTL variants, which may affect the gene expression, to compare the genomic characteristics of TMPRSS2 among different populations. Our findings suggest that the lung-specific eQTL variants may confer different susceptibility or response to SARS-CoV-2 infection from different populations under the similar conditions. In particular, we found that the eQTL variant rs35074065 is associated with high expression of TMPRSS2 but with a low expression of the interferon (IFN)-α/β-inducible gene, MX1, splicing isoform. Thus, these subjects could account for a more susceptibility either to viral infection or to a decrease in cellular antiviral response.

positive: Animal models for the risk assessment of viral pandemic potential Pandemics affect human lives severely and globally. Experience predicts that there will be a pandemic for sure although the time is unknown. When a viral epidemic breaks out, assessing its pandemic risk is an important part of the process that characterizes genomic property, viral pathogenicity, transmission in animal model, and so forth. In this review, we intend to figure out how a pandemic may occur by looking into the past influenza pandemic events. We discuss interpretations of the experimental evidences resulted from animal model studies and extend implications of viral pandemic potentials and ingredients to emerging viral epidemics. Focusing on the pandemic potential of viral infectious diseases, we suggest what should be assessed to prevent global catastrophes from influenza virus, Middle East respiratory syndrome coronavirus, dengue and Zika viruses.

positive: Origin and Evolution of the 2019 Novel Coronavirus

positive: Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV) Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

positive: The possible beneficial adjuvant effect of influenza vaccine to minimize the severity of COVID-19

positive: Laboratory data analysis of novel coronavirus (COVID-19) screening in 2510 patients Abstract Background Novel coronavirus (COVID-19) is highly infectious and requires early detection, isolation, and treatment. We tried to find some useful information by analyzing the covid-19 screening data, so as to provide help for clinical practice. Method We collected nucleic acid and hematology data from 2510 patients for COVID-19 infection for retrospective analysis. Result COVID-19 and influenza A and B infection rates were 1.3%, 3%, and 3%, respectively. COVID-19 nucleic acid was detected in stool but not in tear samples from 8 positive patients. Among the 32 patients with COVID-19, 15 (47%) and 16 (50%) patients showed decreased lymphocyte count and lymphocyte ratio, 21(66%) and 24(75%) patients showed decreased eosinophil count and eosinophil ratio, and 18 (56%) patients showed increased C-reactive protein. Ten hematological indicators significantly differed in the blood of patients with COVID-19 and those with influenza A and B (P < 0.05). Eighteen hematological indicators significantly differed between patients with COVID-19 and negative patients (P < 0.05). Conclusion The positive rate of influenza A and B infection was higher than that of COVID-19. When pharyngeal swab collection may cause infection, fecal samples can be examined. Evaluation of pharyngeal swab and fecal samples can improve the positive rate of nucleic acid detection. The COVID-19 can cause some hematological indices changes.

positive: Social Distancing against COVID-19: Implication for the Control of Influenza Social distancing has been adopted as one of basic protective measures against coronavirus disease 2019 (COVID-19). During 2019–2020 season, influenza epidemic period was exceptionally short and epidemic peak was low in comparison with previous seasons in Korea. Influenza epidemic pattern was bimodal in 2016–2017 and 2018–2019 seasons, however, influenza viruses have rarely been circulating in spring, 2020 in Korea. Although multiple factors could affect the size of influenza epidemic, extensive application of nonpharmaceutical interventions including mask wearing and social distancing in response to COVID-19 seems to be a major factor of reduced influenza epidemic. Social distancing measures with high feasibility and high acceptability should be implemented even if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are developed in the future. Establishment of guideline for workplace social distancing is needed and it would contribute to reduce disease burden of influenza, especially in vaccine mismatch year.

positive: Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study) Background There is no specific antiviral therapy recommended for the disease caused by SARS-CoV-2 (COVID-19). Recent publications have drawn attention to the possible benefit of chloroquine (CQ). Our study aimed to comprehensively evaluate the safety and efficacy of two different CQ dosages in patients with established severe COVID-19. Methods We performed a parallel, double-blinded, randomized, phase IIb clinical trial, aiming to assess safety and efficacy of two different CQ dosages as adjunctive therapy of hospitalized patients with SARS in Manaus, Brazilian Amazon. Eligible participants were allocated to receive orally or via nasogastric tube high dose CQ (600mg CQ twice daily for 10 days or total dose 12g); or low dose CQ (450mg for 5 days, twice daily only on the first day, or total dose 2.7g). In addition, all patients received ceftriaxone and azithromycin. This study was registered with ClinicalTrials.gov, number NCT04323527. Findings Out of a pre-defined 440 patients sample size, 81 patients were enrolled. The high dose CQ arm presented more QTc>500ms (25%), and a trend toward higher lethality (17%) than the lower dosage. Fatality rate was 13.5% (95%CI=6.9-23.0%), overlapping with the CI of historical data from similar patients not using CQ (95%CI=14.5-19.2%). In 14 patients with paired samples, respiratory secretion at day 4 was negative in only one patient. Interpretation Preliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards. Such results forced us to prematurely halt patient recruitment to this arm. Given the enormous global push for the use of CQ for COVID-19, results such as the ones found in this trial can provide robust evidence for updated COVID-19 patient management recommendations.

positive: Comparison of short-term mortality between mechanically ventilated patients with COVID-19 and influenza in a setting of sustainable healthcare system

positive: The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection. SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2 114 269 people, resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

positive: A consideration of publication-derived immune-related associations in Coronavirus and related lung damaging diseases The severe acute respiratory syndrome virus SARS-CoV-2, a close relative of the SARS-CoV virus, is the cause of recent COVID-19 pandemic affecting, to date, over a 2 million individuals across the globe and demonstrating relatively high rates of infection and mortality. A third virus, the H5N1, responsible for avian influenza, has caused infection with some clinical similarities to those in COVID-19 infections. Cytokines, small proteins that modulate immune responses, have been directly implicated in some of the severe responses seen in COVID-19 patients, e.g. cytokine storms. Understanding the immune processes related to COVID-19, and other similar infections, could help identify diagnostic markers and therapeutic targets. Here we examine data of cytokine, immune cell types, and disease associations captured from biomedical literature associated with coronavirus, SARS, and H5N1 influenza, with the objective of identifying potentially useful relationships and areas for future research. Cytokine and cell-type associations captured from MeSH terms linked to thousands of PubMed abstracts, has identified differing patterns of associations between the three corpuses of abstracts (coronavirus, SARS, or H5N1 influenza). Clustering of cytokine-disease co-occurrences in the context of coronavirus has identified compelling clusters of co-morbidities and symptoms, some of which already known to be linked to COVID-19. Finally, network analysis identified sub-networks of cytokines and immune cell types associated with different manifestations, co-morbidities and symptoms of coronavirus, SARS, and H5N1. Systematic review of research in medicine is essential to facilitate evidence-based choices about health interventions. In a fast moving pandemic the approach taken here will identify trends and enable rapid comparison to the literature of related diseases.

positive: Early surveillance and public health emergency disposal measures between novel coronavirus disease 2019 and avian influenza in China: a case-comparison study Background: The novel coronavirus disease 2019 (COVID-19) outbreak is spreading rapidly throughout China and the world. Hence, early surveillance and public health emergency disposal are considered crucial to curb this emerging infectious disease. However, studies that investigated the early surveillance and public health emergency disposal for the prevention and control of the COVID-19 outbreak in China are relatively few. We aimed to compare the strengths and weaknesses of early surveillance and public health emergency disposal for prevention and control between COVID-19 and H7N9 avian influenza, which was commended by the international community, in China. Methods: A case-comparison study was conducted using a set of six key time nodes to form a reference framework for evaluating early surveillance and public health emergency disposal between H7N9 avian influenza (2013) in Shanghai, China and COVID-19 in Wuhan, China. Findings: A report to the local Center for Disease Control and Prevention, China, for the first hospitalized patient was sent after 6 and 20 days for H7N9 avian influenza and COVID-19, respectively. In contrast, the pathogen was identified faster in the case of COVID-19 than in the case of H7N9 avian influenza (12 days vs. 31 days). The government response regarding COVID-19 was 10 days later than that regarding avian influenza. The entire process of early surveillance and public health emergency disposal lasted 5 days longer in COVID-19 than in H7N9 avian influenza (46 days vs. 41 days). Conclusions: The identification of the unknown pathogen improved in China between the outbreaks of avian influenza and COVID-19. The longer emergency disposal period in the case of COVID-19 could be attributed to the government's slower response to the epidemic. Improving public health emergency management could lessen the adverse social effects of emerging infectious diseases and public health crisis in the future.

positive: Seasonal and pandemic influenza: 100 years of progress, still much to learn Influenza viruses are highly transmissible, both within and between host species. The severity of the disease they cause is highly variable, from the mild and inapparent through to the devastating and fatal. The unpredictability of epidemic and pandemic outbreaks is accompanied but the predictability of seasonal disease in wide areas of the Globe, providing an inexorable toll on human health and survival. Although there have been great improvements in understanding influenza viruses and the disease that they cause, our knowledge of the effects they have on the host and the ways that the host immune system responds continues to develop. This review highlights the importance of the mucosa in defence against infection and in understanding the pathogenesis of disease. Although vaccines have been available for many decades, they remain suboptimal in needing constant redesign and in only providing short-term protection. There are real prospects for improvement in treatment and prevention of influenza soon, based on deeper knowledge of how the virus transmits, replicates and triggers immune defences at the mucosal surface.

positive: SARS – CoV -2: reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis) Abstract The novel coronavirus COVID-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against COVID-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics (“Spanish flu” 1918, “Asian flu” 1956 and “the Hong Kong flu” 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4+ memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4+ memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting “lung crash” until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the COVID-19 will occur.

positive: A new dawn for the management of influenza?

positive: Social Distancing and Personal Protective Measures Decrease Influenza Morbidity and Mortality Seasonal influenza (flu) is an underappreciated source of disease morbidity and mortality worldwide. While vaccination remains the cornerstone of influenza prevention, common measures practiced during the COVID-19 pandemic such as social distancing, the use of protective face masks, and frequent hand washing are rarely utilized during flu season. In this investigation, we examined the effect of these preventative measures in decreasing influenza burden this year. We examined three countries with major COVID-19 outbreaks i.e. China, Italy and the United States, and compared the flu activity this year to the average of the last 4 years (2015-2019). We found that this year in China and Italy, there was a significantly steeper decline of flu cases than average, which correlated with an increase in positive COVID-19 case reports in those countries. These "averted" cases can be translated into a substantial decrease in morbidity and mortality. As such, we conclude that the current COVID-19 pandemic is a reminder that behavioral measures can decrease the burden of communicable respiratory infections, and these measures should be adopted to an extent during normal influenza season.

positive: Spread of SARS-CoV-2 Coronavirus likely to be constrained by climate As new cases of COVID-19 are being confirmed pressure is mounting to increase understanding of the factors underlying the spread the disease. Using data on local transmissions until the 23rd of March 2020, we develop an ensemble of 200 ecological niche models to project monthly variation in climate suitability for spread of SARS-CoV-2 throughout a typical climatological year. Although cases of COVID-19 are reported all over the world, most outbreaks display a pattern of clustering in relatively cool and dry areas. The predecessor SARS-CoV-1 was linked to similar climate conditions. Should the spread of SARS CoV-2 continue to follow current trends, asynchronous seasonal global outbreaks could be expected. According to the models, temperate warm and cold climates are more favorable to spread of the virus, whereas arid and tropical climates are less favorable. However, model uncertainties are still high across much of sub- Saharan Africa, Latin America and South East Asia. While models of epidemic spread utilize human demography and mobility as predictors, climate can also help constrain the virus. This is because the environment can mediate human-to-human transmission of SARS-CoV-2, and unsuitable climates can cause the virus to destabilize quickly, hence reducing its capacity to become epidemic.

positive: Pattern of early human-to-human transmission of Wuhan 2019-nCoV On December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number, R0, to be around 2.2 (90% high density interval 1.4—3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.

positive: The Emerging Pandemic of Coronavirus and the Urgent Need for Public Health Leadership

positive: Mutations, Recombination and Insertion in the Evolution of 2019-nCoV The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

positive: SARS-CoV-2 (COVID-19) by the numbers The COVID-19 pandemic is a harsh reminder of the fact that, whether in a single human host or a wave of infection across continents, viral dynamics is often a story about the numbers. In this article we provide a one-stop, curated graphical source for the key numbers (based mostly on the peer-reviewed literature) about the SARS-CoV-2 virus that is responsible for the pandemic. The discussion is framed around two broad themes: i) the biology of the virus itself; ii) the characteristics of the infection of a single human host.

positive: Are co-infections with COVID-19 and Influenza low or underreported? An observational study examining current published literature including three new unpublished cases As the COVID-19 pandemic continues, one major point of uncertainty is the impact this novel pathogen will have during the upcoming 2020-2021 flu season. While the influenza virus is a known contributor to human morbidity and mortality, the question of how a coinfection between COVID-19 and influenza might manifest is of utmost concern. The aim of this study was to review the limited cases of COVID-19/influenza coinfection currently available in the literature, along with cases in the community of El Paso, Texas, to determine whether any patterns of clinical presentation and morbidity emerged. An international review of the literature was conducted. Six published articles describing COVID-19/influenza coinfection were identified, with a total of thirteen patients described therein. Three additional patients were identified from the El Paso, Texas data. The most common presenting symptoms were fever and cough. The most common laboratory findings were elevated C-reactive protein and lymphocytopenia. Thirteen patients presented with viral pneumonia findings on CT, and nine had findings of ground-glass opacity. Finally, complications were reported in six patients, with most common complication being acute respiratory distress syndrome (ARDS). The results of the review indicate that, due to the similarity in presentation between COVID-19 and influenza, further analysis will be required to understand the effects of coinfection on morbidity and mortality. However, the limited number of coinfection cases in the literature indicates that the implementation of COVID-19 control measures may continue to play a role in limiting the spread of these human respiratory pathogens. This article is protected by copyright. All rights reserved.

positive: How coronavirus lockdowns stopped flu in its tracks.

positive: The dynamic effects of infectious disease outbreaks: The case of pandemic influenza and human coronavirus Pandemic influenza is a regularly recurring form of infectious disease; this work analyses its economic effects. Like many other infectious diseases influenza pandemics are usually of short, sharp duration. Human coronavirus is a less regularly recurring infectious disease. The human coronavirus pandemic of 2019 (COVID-19) has presented with seemingly high transmissibility and led to extraordinary socioeconomic disruption due to severe preventative measures by governments. To understand and compare these events, epidemiological and economic models are linked to capture the transmission of a pandemic from regional populations to regional economies and then across regional economies. In contrast to past pandemics, COVID-19 is likely to be of longer duration and more severe in its economic effects given the greater uncertainty surrounding its nature. The analysis indicates how economies are likely to be affected due to the risk-modifying behaviour in the form of preventative measures taken in response to the latest novel pandemic virus.

positive: Influenza, Measles, SARS, MERS, and Smallpox Influenza, measles, SARS, MERS, and smallpox illnesses are caused by highly infectious viral pathogens that induce critical illness. These biologically diverse viruses enter and replicate within host cells triggering viral- and host-mediated damage that results in pneumonia and multiorgan failure in severe cases. Early case identification and strict infection control limit healthcare transmission. Vaccination allowed smallpox eradication and limits global measles and seasonal influenza mortality. While SARS-coronavirus (CoV) is no longer circulating, MERS-CoV and zoonotic influenza viruses, with pandemic potential, remain persistent threats. Supportive critical care is the mainstay of treatment for severe disease due to these viral infections.

positive: Gilles de la Tourette Syndrome: advice in the times of COVID-19 The novel coronavirus disease (COVID-19) was identified as the cause of an outbreak of respiratory disease in China at the end of 2019. It then spread with enormous rapidity and by mid-March 2020 was declared a world pandemic. Gilles de la Tourette Syndrome (GTS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 1% of the population. The clinical symptoms include multiple motor and one or more phonic (vocal) tics. Germane to this communication is that 85% of patients with GTS have associated psychiatric co-morbidities, many of which are being exacerbated in the current global health crisis. In addition, several symptoms of GTS may mimic COVID-19, such as a dry cough and sniffing (phonic tics), while other symptoms such as spitting, inappropriate touching of others and “non-obscene socially inappropriate symptoms” can potentially get patients with GTS into trouble with the law. We suggest that a clear explanation of the COVID-19 illness and GTS is important to enable colleagues of various specialities who tend to patients with GTS. It is important to acknowledge at the outset that the information available on the COVID-19 pandemic changes daily, including cases infected, deaths reported, and how various national health systems are planning and or coping or not. It is fair to say that having read the current medical and lay press we conclude that it is not easy to reassure our patients with absolute certainty. However, notwithstanding that, we hope our documentation is of some assistance.

positive: Susceptibility and Sustainability of India against CoVid19: a multivariate approach Purpose: We are currently in the middle of a global crisis. Covid19 pandemic has suddenly threatened the existence of human life. Till date, as no medicine or vaccine is discovered, the best way to fight against this pandemic is prevention. The impact of different environmental, social, economic and health parameters is unknown and under research. It is important to identify the factors which can weaken the virus, and the nations which are more vulnerable to this virus. Materials and Methods: Data of weather, vaccination trends, life expectancy, lung disease, number of infected people in the pre-lockdown and post-lockdown period of highly infected nations are collected. These are extracted from authentic online resources and published reports. Analysis is done to find the possible impact of each parameter on CoVid19. Results: CoVid19 has no linear correlation with any of the selected parameters, though few parameters have depicted non-linear relationship in the graphs. Further investigations have shown better result for some parameters. A combination of the parameters results in a better correlation with infection rate. Conclusions: Though depending on the study outcome, the impact of CoVid19 in India can be predicted, the required lockdown period cannot be calculated due to data limitation.

positive: Scientometric Trends for Coronaviruses and Other Emerging Viral Infections COVID-19 is the most rapidly expanding coronavirus outbreak in the past two decades. To provide a swift response to a novel outbreak, prior knowledge from similar outbreaks is essential. Here, we study the volume of research conducted on previous coronavirus outbreaks, specifically SARS and MERS, relative to other infectious diseases by analyzing over 35 million papers from the last 20 years. Our results demonstrate that previous coronavirus outbreaks have been understudied compared to other viruses. We also show that the research volume of emerging infectious diseases is very high after an outbreak and drops drastically upon the containment of the disease. This can yield inadequate research and limited investment in gaining a full understanding of novel coronavirus management and prevention. Independent of the outcome of the current COVID-19 outbreak, we believe that measures should be taken to encourage sustained research in the field.

positive: Novel Coronavirus Disease (COVID-19) The present outbreak of the novel coronavirus initially called as “2019 novel coronavirus” or “2019-nCoV” by the World Health Organization (WHO), is also known as “Wuhan coronavirus” or “Wuhan pneumonia”, as it started in the Wuhan city of China in early December of 2019. This new coronavirus-associated acute respiratory deadly disease is now officially named as Corona Virus Disease-19 (COVID-19) by the WHO. From China, this epidemic has now spread to all over the world. On 11 March 2020, the WHO recognised COVID-19 as a pandemic. A pandemic refers to a disease that has spread to several countries, continents, if not worldwide. While the information available on this newly identified virus is limited and evolving, here is a quick run-down of what has been figured out so far.

positive: The burden of seasonal respiratory infections on a national telehealth service in England. Seasonal respiratory illnesses present a major burden on primary care services. We assessed the burden of respiratory illness on a national telehealth system in England and investigated the potential for providing early warning of respiratory infection. We compared weekly laboratory reports for respiratory pathogens with telehealth calls (NHS 111) between week 40 in 2013 and week 29 in 2015. Multiple linear regression was used to identify which pathogens had a significant association with respiratory calls. Children aged <5 and 5-14 years, and adults over 65 years were modelled separately as were time lags of up to 4 weeks between calls and laboratory specimen dates. Associations with respiratory pathogens explained over 83% of the variation in cold/flu, cough and difficulty breathing calls. Based on the first two seasons available, the greatest burden was associated with respiratory syncytial virus (RSV) and influenza, with associations found in all age bands. The most sensitive signal for influenza was calls for 'cold/flu', whilst for RSV it was calls for cough. The best-fitting models showed calls increasing a week before laboratory specimen dates. Daily surveillance of these calls can provide early warning of seasonal rises in influenza and RSV, contributing to the national respiratory surveillance programme.

positive: Non-pharmaceutical interventions used for COVID-19 had a major impact on reducing influenza in China in 2020 Stringent non-pharmaceutical measures to contain the COVID-19 outbreak in China also significantly reduced the spread of influenza in the winter season 2020.

positive: Coronavirus SARS‐CoV‐2: filtering fact from fiction in the infodemic: Q&A with virologist Professor Urs Greber As the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) continues to spread across the world, and the associated lung disease COVID-19 remains difficult to treat, information from media and private communication flows at high speed, often through unfiltered channels. Much of this information is speculative, as it derives from preliminary and inconclusive studies, and creates confusion as well as anxiety. This phenomenon was recently labelled as "infodemic" by the World Health Organization.

positive: Studying Communication Problems for Emergency Management of SARS and H7N9 in China BACKGROUND: Severe Acute Respiratory Syndrome (SARS) and Influenza A virus Subtype H7N9 (H7N9) have both had a great impact on China in the 21(st) century, causing significant negative impacts on health, the economy, and even global security. The control efforts for SARS were heavily criticized, the H7N9 response, 10 years later was acknowledged to be much better. AIMS: This article explores communication for emergency management of SARS in 2003 and H7N9 in 2013 in China, to provide useful evidence for government and practitioner on management improvement for infectious disease outbreaks response in China and international community in the future. METHODS: This study uses a qualitative case study approach, including in-depth interviews, literature review, and document, to analysis the emergency management of SARS in 2003 and H7N9 in 2013 in China, identified the problems of communication with the emergency management process for SARS and H7N9. RESULTS: The control efforts for SARS were slow to be mobilized and were heavily criticized and generally considered to be suboptimal, as the poor handling of SARS exposed serious communication problems in the then emergency management system processes. The H7N9 response, 10 years later, was acknowledged to be much better. CONCLUSION: Communication is very important in the prevention and control of infectious diseases. From SARS to H7N9, the progress had been made in information disclosure.

positive: Guidelines for preventing respiratory illness in older adults aged 60 years and above living in long-term care: A rapid review of clinical practice guidelines Background: The overall objective of this rapid review was to identify infection protection and control recommendations from published clinical practice guidelines (CPGs) for adults aged 60 years and older in long-term care settings Methods: Comprehensive searches in MEDLINE, EMBASE, the Cochrane Library, and relevant CPG publishers/repositories were carried out in early March 2020. Title/abstract and full-text screening, data abstraction, and quality appraisal (AGREE-II) were carried out by single reviewers. Results: A total of 17 relevant CPGs were identified, published in the USA (n=8), Canada (n=6), Australia (n=2), and the United Kingdom (n=1). All of the CPGs dealt with infection control in long-term care facilities (LTCF) and addressed various types of viral respiratory infections (e.g., influenza, COVID-19, severe acute respiratory syndrome). Ten or more CPGs recommended the following infection control measures in LTCF: hand hygiene (n=13), wearing personal protective equipment (n=13), social distancing or isolation (n=13), disinfecting surfaces (n=12), droplet precautions (n=12), surveillance and evaluation (n=11), and using diagnostic testing to confirm illness (n=10). While only two or more CPGs recommended these infection control measures: policies and procedures for visitors, staff and/or residents (n=9), respiratory hygiene/cough etiquette (n=9), providing supplies (n=9), staff and/or residents education (n=8), increasing communication (n=6), consulting or notifying health professionals (n=6), appropriate ventilation practices (n=2), and cohorting equipment (n=2). Ten CPGs also addressed management of viral respiratory infections in LTCF and recommended antiviral chemoprophylaxis (n=10) and one CPG recommended early mobilization of residents. Conclusion: The recommendations from current guidelines overall seem to support environmental measures for infection prevention and antiviral chemoprophylaxis for infection management as the most appropriate first-line response to viral respiratory illness in long-term care.

positive: Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan Abstract Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital. Methods Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray™ Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections. Results Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.

positive: Comparative seasonalities of influenza A, B and 'common cold' coronaviruses - setting the scene for SARS-CoV-2 infections and possible unexpected host immune interactions

positive: Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease 2019 Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

positive: Epidemiology, virology, and clinical features of severe acute respiratory syndrome -coronavirus-2 (SARS-CoV-2; Coronavirus Disease-19) A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been 2 novel coronavirus outbreaks in the past 2 decades. The outbreak of severe acute respiratory syndrome (SARS) in 2002–2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 deaths), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features.

positive: Infectious diseases in children and adolescents in China: analysis of national surveillance data from 2008 to 2017 OBJECTIVES: To outline which infectious diseases in the pre-covid-19 era persist in children and adolescents in China and to describe recent trends and variations by age, sex, season, and province. DESIGN: National surveillance studies, 2008-17. SETTING: 31 provinces in mainland China. PARTICIPANTS: 4 959 790 Chinese students aged 6 to 22 years with a diagnosis of any of 44 notifiable infectious diseases. The diseases were categorised into seven groups: quarantinable; vaccine preventable; gastrointestinal and enteroviral; vectorborne; zoonotic; bacterial; and sexually transmitted and bloodborne. MAIN OUTCOME MEASURES: Diagnosis of, and deaths from, 44 notifiable infectious diseases. RESULTS: From 2008 to 2017, 44 notifiable infectious diseases were diagnosed in 4 959 790 participants (3 045 905 males, 1 913 885 females) and there were 2532 deaths (1663 males, 869 females). The leading causes of death among infectious diseases shifted from rabies and tuberculosis to HIV/AIDS, particularly in males. Mortality from infectious diseases decreased steadily from 0.21 per 100 000 population in 2008 to 0.07 per 100 000 in 2017. Quarantinable conditions with high mortality have effectively disappeared. The incidence of notifiable infectious diseases in children and adolescents decreased from 280 per 100 000 in 2008 to 162 per 100 000 in 2015, but rose again to 242 per 100 000 in 2017, largely related to mumps and seasonal influenza. Excluding mumps and influenza, the incidence of vaccine preventable diseases fell from 96 per 100 000 in 2008 to 7 per 100 000 in 2017. The incidence of gastrointestinal and enterovirus diseases remained constant, but typhoid, paratyphoid, and dysentery continued to decline. Vectorborne diseases all declined, with a particularly noticeable reduction in malaria. Zoonotic infections remained at low incidence, but there were still unpredictable outbreaks, such as pandemic A/H1N1 2009 influenza. Tuberculosis remained the most common bacterial infection, although cases of scarlet fever doubled between 2008 and 2017. Sexually transmitted diseases and bloodborne infections increased significantly, particularly from 2011 to 2017, among which HIV/AIDS increased fivefold, particularly in males. Difference was noticeable between regions, with children and adolescents in western China continuing to carry a disproportionate burden from infectious diseases. CONCLUSIONS: China's success in infectious disease control in the pre-covid-19 era was notable, with deaths due to infectious diseases in children and adolescents aged 6-22 years becoming rare. Many challenges remain around reducing regional inequalities, scaling-up of vaccination, prevention of further escalation of HIV/AIDS, renewed efforts for persisting diseases, and undertaking early and effective response to highly transmissible seasonal and unpredictable diseases such as that caused by the novel SARS-CoV-2 virus.

positive: COVID-19 is not just a flu. Learn from Italy and act now

positive: Interest of a simple on-line screening registry for measuring ICU burden related to an influenza pandemic INTRODUCTION: The specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored. An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs. METHODS: We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden. RESULTS: Among the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry. The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non-infected patients for at least three weeks. Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died. The global Flu-OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks. Flu-ORs were significantly higher in University than in non-University hospitals. The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas. CONCLUSIONS: The peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals. An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs.

positive: Genomic Epidemiology and its importance in the study of the COVID-19 pandemic Not available.

positive: Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study BACKGROUND: A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong. We examined the effect of these interventions and behavioural changes of the public on the incidence of COVID-19, as well as on influenza virus infections, which might share some aspects of transmission dynamics with COVID-19. METHODS: We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (Rt) for COVID-19 and influenza A H1N1 to estimate changes in transmissibility over time. Attitudes towards COVID-19 and changes in population behaviours were reviewed through three telephone surveys done on Jan 20-23, Feb 11-14, and March 10-13, 2020. FINDINGS: COVID-19 transmissibility measured by Rt has remained at approximately 1 for 8 weeks in Hong Kong. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% CI 34-53%) reduction in transmissibility in the community, from an estimated Rt of 1·28 (95% CI 1·26-1·30) before the start of the school closures to 0·72 (0·70-0·74) during the closure weeks. Similarly, a 33% (24-43%) reduction in transmissibility was seen based on paediatric hospitalisation rates, from an Rt of 1·10 (1·06-1·12) before the start of the school closures to 0·73 (0·68-0·77) after school closures. Among respondents to the surveys, 74·5%, 97·5%, and 98·8% reported wearing masks when going out, and 61·3%, 90·2%, and 85·1% reported avoiding crowded places in surveys 1 (n=1008), 2 (n=1000), and 3 (n=1005), respectively. INTERPRETATION: Our study shows that non-pharmaceutical interventions (including border restrictions, quarantine and isolation, distancing, and changes in population behaviour) were associated with reduced transmission of COVID-19 in Hong Kong, and are also likely to have substantially reduced influenza transmission in early February, 2020. FUNDING: Health and Medical Research Fund, Hong Kong.

positive: Viruses of Respiratory Tract: an Observational Retrospective Study on Hospitalized Patients in Rome, Italy Respiratory tract infections account for high morbidity and mortality around the world. Fragile patients are at high risk of developing complications such as pneumonia and may die from it. Limited information is available on the extent of the circulation of respiratory viruses in the hospital setting. Most knowledge relates to influenza viruses (FLU) but several other viruses produce flu-like illness. The study was conducted at the University Hospital Policlinico Tor Vergata, Rome, Italy. Clinical and laboratory data from hospitalized patients with respiratory tract infections during the period October 2016–March 2019 were analysed. The retrospective analysis included 17 viral agents detected by FilmArray test and clinical data from medical records and hospital discharge sheets. Models were adjusted for relevant confounders such as clinical severity and risk of death, socio-demographic characteristics and surgical procedures. From a total of 539 specimens analysed, 180 (33.39%) were positive for one or more respiratory viruses. Among them, 83 (46.1 %) were positive for influenza viruses (FLU), 36 (20%) rhino/enteroviruses (RHV/EV), 17 (9.44%) human coronaviruses (HCOV-229E, -HKU1, -NL63, and -OC43), 17 (9.44%) respiratory syncytial virus, 15 (8.33%) human metapneumovirus (HMPV), 8 (4.44%) parainfluenza viruses (PIV) and 4 (2.22%) adenoviruses (ADV). The distribution of viral agents varied across age groups and month of detection. The positive specimens were from 168 patients [102 M, 66 F; median age (range): 64 years (19−93)]. Overall, 40% of them had a high-grade clinical severity and a 27% risk of death; 27 patients died and 22 of them (81.5%) had received a clinical diagnosis of pneumonia. Respiratory viral infections may have a severe course and a poor prognosis in hospitalized patients, due to underlying comorbidities. Monitoring the circulation of respiratory viruses in hospital settings is important to improve diagnosis, prevention and treatment.

positive: News from the front: Excess mortality and life expectancy in two major epicentres of the COVID-19 pandemic in Italy Existing studies commonly rely on national official reports to estimate the impact of COVID-19 on population health and human life. However, relying on national reports is problematic because classification and estimation of COVID-19 mortality are not consistent across countries. Likewise, delay coronavirus test results and shortage of testing kits can result in undercounting of coronavirus deaths. To overcome these problems, this study exploits all cause daily death registrations data provide by the Italian Statistical Office (ISTAT) from 1st January to 4th April 2020. This allows us to: 1) calculate excess mortality in 2020 compared to the years 2015 to 2019; and 2) estimate life expectancy on a seasonal and annual basis. We focus our analysis on Bergamo and Brescia, the two hardest hit provinces in Lombardy, northern Italy. Given the clustering nature of the epidemic, focusing on the areas with high concentration of severe illness and deaths allows us to capture the true impact of COVID-19 on mortality and life expectancy, which are likely to be underestimated in the national level data. We find that on the period 1 Jan to 4 April 2020, seasonal life expectancy in Bergamo reduced by around 8.1 and 6.5 years compared to 2019 for men and women respectively (4.5 and 3.4 years in Brescia). The drop in period life expectancy for 2020 may total up to 3 years in the case of men and 2 years in the case of women. Such a sharp decrease in life expectancy has not been experienced in modern history since the Second World War. This study shows that, in the absence of public health interventions to reduce the spread of the virus, COVID-19 has set life expectancy in Bergamo and Brescia back to the Italian life expectancy of 15 years ago.

positive: Abnormal respiratory patterns classifier may contribute to large-scale screening of people infected with COVID-19 in an accurate and unobtrusive manner Research significance: During the epidemic prevention and control period, our study can be helpful in prognosis, diagnosis and screening for the patients infected with COVID-19 (the novel coronavirus) based on breathing characteristics. According to the latest clinical research, the respiratory pattern of COVID-19 is different from the respiratory patterns of flu and the common cold. One significant symptom that occurs in the COVID-19 is Tachypnea. People infected with COVID-19 have more rapid respiration. Our study can be utilized to distinguish various respiratory patterns and our device can be preliminarily put to practical use. Demo videos of this method working in situations of one subject and two subjects can be downloaded online. Research details: Accurate detection of the unexpected abnormal respiratory pattern of people in a remote and unobtrusive manner has great significance. In this work, we innovatively capitalize on depth camera and deep learning to achieve this goal. The challenges in this task are twofold: the amount of real-world data is not enough for training to get the deep model; and the intra-class variation of different types of respiratory patterns is large and the outer-class variation is small. In this paper, considering the characteristics of actual respiratory signals, a novel and efficient Respiratory Simulation Model (RSM) is first proposed to fill the gap between the large amount of training data and scarce real-world data. Subsequently, we first apply a GRU neural network with bidirectional and attentional mechanisms (BI-AT-GRU) to classify 6 clinically significant respiratory patterns (Eupnea, Tachypnea, Bradypnea, Biots, Cheyne-Stokes and Central-Apnea). The proposed deep model and the modeling ideas have the great potential to be extended to large scale applications such as public places, sleep scenario, and office environment.

positive: From SARS to COVID-19: A previously unknown SARS- related coronavirus (SARS-CoV-2) of pandemic potential infecting humans – Call for a One Health approach Human coronaviruses continue to pose a threat to human health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 which causes coronavirus disease-2019 (COVID-19), an acute respiratory disease marked the third introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. This recent emergence of a previously unknown coronavirus in China leads to huge impacts on humans globally. Covid-19 is a challenge to global public health. Here, we discuss the COVID-19 outbreak in a one health context, highlighting the need for the implementation of one health measures and practices to improve human health and reduce the emergence of pandemic viruses.

positive: The epidemiology and clinical characteristics of co‐infection of SARS‐CoV‐2 and influenza viruses in patients during COVID‐19 outbreak In this study, we performed a single‐centred study of 307 SARS‐CoV‐2 infected patients. It was found that co‐infection of SARS‐CoV‐2 and influenza virus was common during COVID‐19 outbreak. And patients co‐infected with SARS‐CoV‐2 and influenza B virus have a higher risk of developing poor outcomes so a detection of both viruses was recommended during COVID‐19 outbreak. This article is protected by copyright. All rights reserved.

positive: Alterations of the Gut Microbiota in Patients with COVID-19 or H1N1 Influenza BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and SARS-CoV-2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. METHODS: We conducted a cross-sectional study of 30 COVID-19 patients, 24 influenza A (H1N1) patients, and 30 matched healthy controls (HC) to identify differences in the gut microbiota by 16S ribosomal RNA (rRNA) gene V3-V4 region sequencing. RESULTS: Compared with HC, COVID-19 patients had significantly reduced bacterial diversity, a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella and Actinomyces, and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HC with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the two cohorts with an AUC of 0.94. CONCLUSION: The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HC. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.

positive: Estimating the early death toll of COVID-19 in the United States BACKGROUND: Efforts to track the severity and public health impact of the novel coronavirus, COVID-19, in the US have been hampered by testing issues, reporting lags, and inconsistency between states. Evaluating unexplained increases in deaths attributed to broad outcomes, such as pneumonia and influenza (P&I) or all causes, can provide a more complete and consistent picture of the burden caused by COVID-19. METHODS: We evaluated increases in the occurrence of deaths due to P&I above a seasonal baseline (adjusted for influenza activity) or due to any cause across the United States in February and March 2020. These estimates are compared with reported deaths due to COVID-19 and with testing data. RESULTS: There were notable increases in the rate of death due to P&I in February and March 2020. In a number of states, these deaths pre-dated increases in COVID-19 testing rates and were not counted in official records as related to COVID-19. There was substantial variability between states in the discrepancy between reported rates of death due to COVID-19 and the estimated burden of excess deaths due to P&I. The increase in all-cause deaths in New York and New Jersey is 1.5–3 times higher than the official tally of COVID-19 confirmed deaths or the estimated excess death due to P&I. CONCLUSIONS: Excess P&I deaths provide a conservative estimate of COVID-19 burden and indicate that COVID-19-related deaths are missed in locations with inadequate testing or intense pandemic activity.

positive: Emergence of Novel Coronavirus and COVID-19: whether to stay or die out? The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus “SARS-CoV-2” (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect naïve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.

positive: COVID-19: Lessons for an Urban(izing) World The COVID-19 crisis has changed the face of many of our cities and questioned how we should manage urban life in the wake of a pandemic. This Commentary points to the need to learn urban governance lessons and to the potential value of urban experimentation in crisis.

positive: Estimating the Risks from COVID-19 Infection in Adult Chemotherapy Patients The SARS-CoV-2 (COVID-19) novel coronavirus represents a significant health risk, particularly in older patients. Cancer is one of the leading causes of death in most rich countries, and delivering chemotherapy may be associated with increased risk in the presence of a pandemic infection. Estimating this risk is crucial in making decisions about balancing risks and benefits from administering chemotherapy. However, there are no specific data about chemotherapy risks per se. Here we develop a simple model to estimate the potential harms in patients undergoing chemotherapy during a COVID outbreak. We use age-related case fatality rates as a basis for estimating risk, and use previous data from risk of death during influenza outbreaks to estimate the additional risk associated with chemotherapy. We use data from randomised trials to estimate benefit across a range of curative and palliative settings, and address the balance of benefit against the risk of harm. We then use those data to estimate the impact on national chemotherapy delivery patterns.

positive: Positive effects of COVID-19 control measures on influenza prevention Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a pandemic threat to the whole world. At the same time, influenza virus has been active, with influenza virus and SARS-CoV-2 sharing the same transmission routes. This article aims to alert clinicians of the presence of co-infection with these two viruses and to describe the effect of the measures taken to fight COVID-19 on influenza prevention and control.

positive: Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2 The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2.

positive: Histopathology and genetic susceptibility in COVID‐19 pneumonia The clinical features of COVID‐19 range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. Little is known about the mechanisms behind observed episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. As in other diseases, the answer to some of these questions may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping, which enable mechanistic insights into the differences in pathogenesis and underlying immunological and tissue regenerative response patterns. We will aim to provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease.

positive: Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study. RATIONALE A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. OBJECTIVES To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. METHODS We quantified influenza A(H3N2) virus-specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. MEASUREMENTS AND MAIN RESULTS A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. CONCLUSIONS Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.

positive: Complications Among Adults Hospitalized With Influenza: A Comparison of Seasonal Influenza and the 2009 H1N1 Pandemic Background. Persons with influenza can develop complications that result in hospitalization and death. These are most commonly respiratory related, but cardiovascular or neurologic complications or exacerbations of underlying chronic medical conditions may also occur. Patterns of complications observed during pandemics may differ from typical influenza seasons, and characterizing variations in influenza-related complications can provide a better understanding of the impact of pandemics and guide appropriate clinical management and planning for the future. Methods. Using a population-based surveillance system, we compared clinical complications using International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnosis codes in adults hospitalized with seasonal influenza (n = 5270) or 2009 pandemic influenza A(H1N1) (H1N1pdm09; n = 4962). Results. Adults hospitalized with H1N1pdm09 were younger (median age, 47 years) than those with seasonal influenza (median age, 68 years; P < .01), and differed in the frequency of certain underlying medical conditions. Whereas there was similar risk for many influenza-associated complications, after controlling for age and type of underlying medical condition, adults hospitalized with H1N1pdm09 were more likely to have lower respiratory tract complications, shock/sepsis, and organ failure than those with seasonal influenza. They were also more likely to be admitted to the intensive care unit, require mechanical ventilation, or die. Young adults, in particular, had 2–4 times the risk of severe outcomes from H1N1pdm09 than persons of the same ages with seasonal influenza. Conclusions. Although H1N1pdm09 was thought of as a relatively mild pandemic, these data highlight the impact of the 2009 pandemic on the risk of severe influenza, especially among younger adults, and the impact this virus may continue to have.

positive: Acceptance and preference for COVID-19 vaccination in health-care workers (HCWs) The objective of the present study is to reveal the acceptance and preference for the 2019 novel coronavirus disease (COVID-19) vaccination in health-care workers (HCWs). We performed an internet-based, region-stratified survey among 352 HCWs and 189 individuals in the general population enrolled on March 17th and 18th 2020 from 26 Chinese provinces. The HCWs developed a more in-depth understanding of SARS-Coronavirus-2 infection and showed a higher tolerance to the future vaccination than the general population. 76.4% of HCWs (vs. 72.5% in the general) showed their willingness to receive vaccination. Potential benefits from COVID-19 outbreak such as seeking influenza (65.3%) or pneumonia (55.7%) vaccination can be gained in HCWs. To estimate the relative effects of attributes influencing vaccination choice in the discrete choice experiment, 7 attributes (3 disease-relevant, 3 vaccine-relevant, and 1 of social acceptance) were identified as key determinants. Among them, disease trend (odds ratio, OR: 4.367 (95%CI, 3.721-5.126) for seasonal epidemic, OR: 3.069 (2.612-3.605) for persistent epidemic, with reference to disappearance in summer), social contacts decisions (0.398: 0.339-0.467 for refusal, 0.414: 0.353-0.487 for neutral, with reference to acceptance) and high possibility of being infected (2.076: 1.776-2.425 for infection probability of 30%+ ) were significantly associated with increased probability of choosing vaccination in the HCWs. In contrast, for the general population, vaccine safety and social contacts decisions were the most important predictors. For COVID-19 vaccination, education in HCWs should be taken as a priority, and further benefits of its recommendation to the general public will also be anticipated.

positive: Characteristics of and Public Health Emergency Responses to COVID-19 and H1N1 Outbreaks: A Case-Comparison Study Background: Recently, the novel coronavirus disease (COVID-19) has already spread rapidly as a global pandemic, just like the H1N1 swine influenza in 2009. Evidences have indicated that the efficiency of emergency response was considered crucial to curb the spread of the emerging infectious disease. However, studies of COVID-19 on this topic are relatively few. Methods: A qualitative comparative study was conducted to compare the timeline of emergency responses to H1N1 (2009) and COVID-19, by using a set of six key time nodes selected from international literature. Besides, we also explored the spread speed and peak time of COVID-19 and H1N1 swine influenza by comparing the confirmed cases in the same time interval. Results: The government’s entire emergency responses to the epidemic, H1N1 swine influenza (2009) completed in 28 days, and COVID-19 (2019) completed in 46 days. Emergency responses speed for H1N1 was 18 days faster. As for the epidemic spread speed, the peak time of H1N1 came about 4 weeks later than that of COVID-19, and the H1N1 curve in America was flatter than COVID-19 in China within the first four months after the disease emerged. Conclusions: The speed of the emergency responses to H1N1 was faster than COVID-19, which might be an important influential factor for slowing down the arrival of the peak time at the beginning of the epidemic. Although COVID-19 in China is coming to an end, the government should improve the public health emergency system, in order to control the spread of the epidemic and lessen the adverse social effects in possible future outbreaks.

positive: Coronavirus disease 2019: The harms of exaggerated information and non‐evidence‐based measures The evolving coronavirus disease 2019 (COVID-19) epidemic1 is certainly cause for concern. Proper communication and optimal decision-making is an ongoing challenge, as data evolve. The challenge is compounded, however, by exaggerated information. This can lead to inappropriate actions. It is important to differentiate promptly the true epidemic from an epidemic of false claims and potentially harmful actions.

positive: Coronavirus research before 2020 is more relevant than ever, especially when interpreted for COVID-19 The speed with which biomedical researchers were able to identify and characterise COVID-19 was clearly due to prior research with other coronaviruses. Early epidemiological comparisons with two previous coronaviruses, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), also made it easier to predict COVID-19's likely spread and lethality. This article assesses whether academic interest in prior coronavirus research has translated into interest in the primary source material, using Mendeley reader counts for early academic impact evidence. The results confirm that SARS and MERS research 2008-2017 experienced anomalously high increases in Mendeley readers in April-May 2020. Nevertheless, studies learning COVID-19 lessons from SARS and MERS or using them as a benchmark for COVID-19 have generated much more academic interest than primary studies of SARS or MERS. Thus, research that interprets prior relevant research for new diseases when they are discovered seems to be particularly important to help researchers to understand its implications in the new context.

positive: High-resolution influenza mapping of a city reveals socioeconomic determinants of transmission within and between urban quarters With two-thirds of the global population projected to be living in urban areas by 2050, understanding the transmission patterns of viral pathogens within cities is crucial for effective prevention strategies. Here, in unprecedented spatial resolution, we analysed the socioeconomic determinants of influenza transmission in a European city. We combined geographical and epidemiological data with whole genome sequencing of influenza viruses at the scale of urban quarters and statistical blocks, the smallest geographic subdivisions within a city. We observed annually re-occurring geographic clusters of influenza incidences, mainly associated with net income, and independent of population density and living space. Vaccination against influenza was also mainly associated with household income and was linked to the likelihood of influenza-like illness within an urban quarter. Transmissions patterns within and between quarters were complex. High-resolution city-level epidemiological studies combined with social science surveys such as this will be essential for understanding seasonal and pandemic transmission chains and delivering tailored public health information and vaccination programs at the municipal level.

positive: There are asymptomatic and pre-symptomatic patients infected with COVID-19. So what? Pandemic response implications Abstract Asymptomatic but infectious people have been reported in many infectious diseases. Asymptomatic and pre-symptomatic carriers would be a hidden reservoir of COVID-19. Aim This review identifies primary empirical evidence about the ability of asymptomatic carriers to infect others with COVID-19 pandemic and reflects on the implications for control measures. Methods A systematic review is followed by a narrative report and commentary inclusion criteria were: studies reporting primary data on asymptomatic or pre-symptomatic patients, who were considered to have passed on COVID-19 infection; and published in indexed journals or in peer review between January 1 and March 31, 2020. Results Nine articles reported on 83 asymptomatic or pre-symptomatic persons. Conclusions The evidence confirms COVID-19 transmission from people who were asymptomatic at the time. A series of implications for health service response are laid out. Keywords: Covid-19, Asymptomatic, Pre-symptomatic, Public Health

positive: Characteristics of and Public Health Emergency Responses to COVID-19 and H1N1 Outbreaks: A Case-Comparison Study BACKGROUND: Recently, the novel coronavirus disease (COVID-19) has already spread rapidly as a global pandemic, just like the H1N1 swine influenza in 2009. Evidences have indicated that the efficiency of emergency response was considered crucial to curb the spread of the emerging infectious disease. However, studies of COVID-19 on this topic are relatively few. METHODS: A qualitative comparative study was conducted to compare the timeline of emergency responses to H1N1 (2009) and COVID-19, by using a set of six key time nodes selected from international literature. Besides, we also explored the spread speed and peak time of COVID-19 and H1N1 swine influenza by comparing the confirmed cases in the same time interval. RESULTS: The government's entire emergency responses to the epidemic, H1N1 swine influenza (2009) completed in 28 days, and COVID-19 (2019) completed in 46 days. Emergency responses speed for H1N1 was 18 days faster. As for the epidemic spread speed, the peak time of H1N1 came about 4 weeks later than that of COVID-19, and the H1N1 curve in America was flatter than COVID-19 in China within the first four months after the disease emerged. CONCLUSIONS: The speed of the emergency responses to H1N1 was faster than COVID-19, which might be an important influential factor for slowing down the arrival of the peak time at the beginning of the epidemic. Although COVID-19 in China is coming to an end, the government should improve the public health emergency system, in order to control the spread of the epidemic and lessen the adverse social effects in possible future outbreaks.

positive: Multicenter Evaluation of the QIAstat-Dx Respiratory Panel for Detection of Viruses and Bacteria in Nasopharyngeal Swab Specimens The QIAstat-Dx Respiratory Panel (QIAstat-Dx RP) is a multiplex in vitro diagnostic test for the qualitative detection of 20 pathogens directly from nasopharyngeal swab (NPS) specimens. The assay is performed using a simple sample-to-answer platform with results available in approximately 69 min. The pathogens identified are adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus A and B, influenza A, influenza A H1, influenza A H3, influenza A H1N1/2009, influenza B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, rhinovirus/enterovirus, respiratory syncytial virus A and B, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. This multicenter evaluation provides data obtained from 1,994 prospectively collected and 310 retrospectively collected (archived) NPS specimens with performance compared to that of the BioFire FilmArray Respiratory Panel, version 1.7. The overall percent agreement between QIAstat-Dx RP and the comparator testing was 99.5%. In the prospective cohort, the QIAstat-Dx RP demonstrated a positive percent agreement of 94.0% or greater for the detection of all but four analytes: coronaviruses 229E, NL63, and OC43 and rhinovirus/enterovirus. The test also demonstrated a negative percent agreement of ≥97.9% for all analytes. The QIAstat-Dx RP is a robust and accurate assay for rapid, comprehensive testing for respiratory pathogens.

positive: Optimizing diagnostic strategy for novel coronavirus pneumonia, a multi-center study in Eastern China COVID-19 caused by a novel coronavirus SARS-CoV-2 emerged in Wuhan, Hubei province since December 2019, and caused a rapid outbreak throughout China and globally. Cities outside Hubei are also facing great challenge and require implementing of effective and feasible strategy in precision diagnosing novel coronavirus pneumonia (NCP). We described a multicenter prospective study on diagnostic strategy of suspected NCP patients from January 22nd to February 9th, 2020 in Eastern China cities. Nasopharyngeal swabs were collected from the patients. The epidemiological characteristics, clinical symptoms, laboratory assessments, and computed tomographic (CT) scans were obtained. Pathogen screen were performed including RT-PCR, multiplex PCR, rapid flu antigen tests and mNGS. We enrolled 53 suspected NCP patients, among whom 20 were laboratory-confirmed. Fourteen (70%) and 3 (15%) patients were positive for the first and second SARS-CoV-2 RT-PCR test, respectively. All NCP patients were positive for mNGS. Chest CT images and the symptoms of early stage NCP patients were similar to other viral pneumonia patients. We identified 11 of 20 co-infections in NCP cases, including regular respiratory virus, fungi and bacteria synchronously. Genomic analysis showed that 8 of 10 cases had no mutation in virus genome, while 2 cases had only one single mutation in N gene. Our study discovered that a combination of chest CT, SARS-CoV-2 RT-PCR and multi-plex PCR is recommended in regions outside Hubei province. Co-infection of other pathogens with SARS-CoV-2 exists and should be acknowledged. Repeated sampling, change of specimen type or metagenomics sequencing could further facilitate during critical clinical cases.

positive: Strand-Specific Dual RNA Sequencing of Bronchial Epithelial Cells Infected with Influenza A/H3N2 Viruses Reveals Splicing of Gene Segment 6 and Novel Host-Virus Interactions. Host-influenza virus interplay at the transcript level has been extensively characterized in epithelial cells. Yet, there are no studies that simultaneously characterize human host and influenza A virus (IAV) genomes. We infected human bronchial epithelial BEAS-2B cells with two seasonal IAV/H3N2 strains, Brisbane/10/07 and Perth/16/09 (reference strains for past vaccine seasons) and the well-characterized laboratory strain Udorn/307/72. Strand-specific RNA sequencing (RNA-seq) of the infected BEAS-2B cells allowed for simultaneous analysis of host and viral transcriptomes, in addition to pathogen genomes, to reveal changes in mRNA expression and alternative splicing (AS). In general, patterns of global and immune gene expression induced by the three IAVs were mostly shared. However, AS of host transcripts and small nuclear RNAs differed between the seasonal and laboratory strains. Analysis of viral transcriptomes showed deletions of the polymerase components (defective interfering-like RNAs) within the genome. Surprisingly, we found that the neuraminidase gene undergoes AS and that the splicing event differs between seasonal and laboratory strains. Our findings reveal novel elements of the host-virus interaction and highlight the importance of RNA-seq in identifying molecular changes at the genome level that may contribute to shaping RNA-based innate immunity.IMPORTANCE The use of massively parallel RNA sequencing (RNA-seq) has revealed insights into human and pathogen genomes and their evolution. Dual RNA-seq allows simultaneous dissection of host and pathogen genomes and strand-specific RNA-seq provides information about the polarity of the RNA. This is important in the case of negative-strand RNA viruses like influenza virus, which generate positive (complementary and mRNA) and negative-strand RNAs (genome) that differ in their potential to trigger innate immunity. Here, we characterize interactions between human bronchial epithelial cells and three influenza A/H3N2 strains using strand-specific dual RNA-seq. We focused on this subtype because of its epidemiological importance in causing significant morbidity and mortality during influenza epidemics. We report novel elements that differ between seasonal and laboratory strains highlighting the complexity of the host-virus interplay at the RNA level.

positive: Inhaled biguanides and mTOR inhibition for influenza and coronavirus (Review) The mammalian target of rapamycin (mTOR) signaling pathway senses and responds to nutrient availability, energy sufficiency, stress, hormones and mitogens to modulate protein synthesis. Rapamycin is a bacterial product that can inhibit mTOR via the PI3K/AKT/mTOR pathway. mTOR signaling is necessary for the development of influenza and modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. In one human study, it was found that the treatment of severe H1N1 influenza‑related pneumonia with rapamycin and steroids improved the outcome. However, in other studies, immunosuppression with systemic steroids, and possibly rapamycin as well, was associated with an increased morbidity/mortality and a prolonged viral replication. In order to avoid the systemic side-effects, some investigators have postulated that the inhalation of rapamycin would be desirable. However, the inhalation of rapamycin, with its well-documented lung toxicity, could be contraindicated. Another class of drug, biguanides, can also inhibit mTOR, but have no lung toxicity. Biguanides are widely used small molecule drugs prescribed as oral anti-diabetics that have exhibited considerable promise in oncology. During the 1971 outbreak of influenza, diabetic patients treated with the biguanides, phenformin and buformin, had a lower incidence of infection than diabetics treated with sulfonylureas or insulin. Both buformin and phenformin reduce the mortality of influenza in mice; phenformin is less effective than buformin. The inhalation of buformin or phenformin for influenza may be an effective novel treatment strategy that would limit the risk of systemic side-effects associated with biguanides due to the low inhaled dose. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2, a virus closely related to the SARS virus. The disease is the cause of the 2019–2020 coronavirus outbreak. It is primarily spread between individuals via small droplets emitted from infected individuals when breathing or coughing. PI3K/AKT/mTOR signaling responses play important roles in MERS-CoV infection and may represent a novel drug target for therapeutic intervention strategies. The present review article discusses the effects of biguanides on influenza and coronavirus.

positive: The anti-influenza virus drug, arbidol is an efficient inhibitor of SARS-CoV-2 in vitro

positive: Positive effects of COVID-19 control measures on influenza prevention Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a pandemic threat to the whole world. At the same time, influenza virus has been active, with influenza virus and SARS-CoV-2 sharing the same transmission routes. This article aims to alert clinicians of the presence of co-infection with these two viruses and to describe the effect of the measures taken to fight COVID-19 on influenza prevention and control.

positive: Coronavirus Disease 2019 (COVID-19): A critical care perspective beyond China

positive: SARS-CoV-2 and influenza virus co-infection

positive: Analysis of Covid-19 and non-Covid-19 viruses including influenza viruses to see the influence of intensive preventive measures among Japanese Severe acute respiratory coronavirus 2 (SARS-CoV-2) spread and cause death in worldwide. The preventative measures and infection control are underway throughout the society and there are signs of convergence in some areas. Other viruses as well as SARS-CoV-2 cause cold-like symptoms and spread in winter. However, it is unclear to what extent SARS-CoV-2, influenza virus and other causative viruses have been prevailed since the preventative measures were implemented. In this study, we conducted multiples PCR and quantitative reverse transcription PCR using nasal swabs from 191 patients with cold-like symptoms in Japan to reveal the causative viruses. As a result, at least one virus were detected in 40 out of 191 (21%) patients. Of these, we frequently identified the human rhinovirus / enterovirus (5.8%, n=11), SARS-CoV-2 (4.2%, n=8) and human metapneumovirus (3.7%, n=7). On the other hand, no influenza virus was detected. These results shows the prevalence of causative viruses after the social preventative measures and implies the difference of infectivity between SARS-CoV-2 and influenza virus.

positive: Characterizing COVID-19 case detection utilizing influenza surveillance data in the United States, January-March, 2020 COVID-19 reached the US in January, 2020, but state and local case detection efforts varied in timing and scale. We conducted a state-level ecological analysis of COVID-19 epidemiology alongside CDC influenza surveillance data and policy timelines. Our findings show wide variation in COVID-19 case detection and influenza-like-illness activity between states.

positive: Risk stratification of hospitalized COVID-19 patients through comparative studies of laboratory results with influenza Background The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season. Methods We compared clinical and laboratory results from 719 influenza and 973 COVID-19 patients from January to April 2020. We compiled laboratory results from the first 14 days of the hospitalized patients using parameters that are most significantly different between COVID-19 and influenza and hierarchically clustered COVID-19 patients based on these data. The clinical outcomes were compared among different clusters. Results Temporal analyses of laboratory results revealed that compared to influenza, patients with COVID-19 exhibited a continued increase in the white blood cell count, rapid decline of hemoglobin, more rapid increase in blood urea nitrogen (BUN) and D-dimer, and higher level of alanine transaminase, C-reactive protein, ferritin, and fibrinogen. Using these results, we sub-classified the COVID-19 patients into 5 clusters through a hierarchical clustering analysis. We then reviewed the medical record of these patients and risk stratified them based on the clinical outcomes. The cluster with the highest risk showed 27.8% fatality, 94% ICU admission, 94% intubation, and 28% discharge rates compared to 0%, 38%, 22%, and 88% in the lowest risk cluster, respectively. Patients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin. Conclusions There are significant differences in the clinical and laboratory courses between COVID-19 and influenza. Risk stratification in hospitalized COVID-19 patients using laboratory data could be useful to predict clinical outcomes and pathophysiology of these patients.

positive: COVID-19: A promising cure for the global panic The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.

positive: Droplet evaporation residue indicating SARS-COV-2 survivability on surfaces SARS-CoV-2 survives and remains viable on surfaces for several days under different environments as reported in recent studies. However, it is unclear how the viruses survive for such a long time and why their survivability varies across different surfaces. To address these questions, we conduct systematic experiments investigating the evaporation of droplets produced by a nebulizer and human-exhaled gas on surfaces. We found that these droplets do not disappear with evaporation, but instead shrink to a size of a few micrometers (referred to as residues), persist for more than 24 hours, and are highly durable against changes of environmental conditions. The characteristics of these residues change significantly across surface types. Specifically, surfaces with high thermal conductivity like copper do not leave any resolvable residues, while stainless steel, plastic, and glass surfaces form residues from a varying fraction of all deposited droplets at 40% relative humidity. Lowering humidity level suppresses the formation of residues while increasing humidity level enhances it. Our results suggest that these microscale residues can potentially insulate the virus against environmental changes, allowing them to survive inhospitable environments and remain infectious for prolonged durations after deposition. Our findings can also be extended to other viruses transmitted through respiratory droplets (e.g., SARS-CoV, flu viruses, etc.), and can thus lead to practical guidelines for disinfecting surfaces and other prevention measures (e.g., humidity control) for limiting viral transmission.

positive: Clinician Mental Health and Well-Being During Global Healthcare Crises: Evidence Learned From Prior Epidemics for COVID-19 Pandemic. Novel coronavirus disease 2019 (COVID-19) is sweeping across the globe, having sickened more than 640,000 people and claimed over 30,000 lives in approximately 202 countries at the time of writing with no sign of slowing down (World Health Organization, 2020). Each time a pandemic or an epidemic disease occurs, such as measles, scarlet fever, HIV/AIDS, Ebola, or the flu of 2013, healthcare professionals are on the front lines, battling diseases and caring for sick and dying patients, even while knowingly putting themselves at risk (Borghese, Di Donato, Ruotolo, & Fiegender, 2020).

positive: The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control A pneumonia outbreak with unknown etiology was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. The causative agent of the outbreak was identified by the WHO as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), producing the disease named coronavirus disease-2019 (COVID-19). The virus is closely related (96.3%) to bat coronavirus RaTG13, based on phylogenetic analysis. Human-to-human transmission has been confirmed even from asymptomatic carriers. The virus has spread to at least 200 countries, and more than 1,700,000 confirmed cases and 111,600 deaths have been recorded, with massive global increases in the number of cases daily. Therefore, the WHO has declared COVID-19 a pandemic. The disease is characterized by fever, dry cough, and chest pain with pneumonia in severe cases. In the beginning, the world public health authorities tried to eradicate the disease in China through quarantine but are now transitioning to prevention strategies worldwide to delay its spread. To date, there are no available vaccines or specific therapeutic drugs to treat the virus. There are many knowledge gaps about the newly emerged SARS-CoV-2, leading to misinformation. Therefore, in this review, we provide recent information about the COVID-19 pandemic. This review also provides insights for the control of pathogenic infections in humans such as SARS-CoV-2 infection and future spillovers.

positive: Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71–77. Background Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods Eight hundred and ninety‐three residual nasal wash samples from children treated for respiratory illness at Children’s Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results Coinfections were identified in 103 (18%) of 566 virus‐positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV‐1, multiple virus illnesses had a significantly lower viral load (log(10) copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu‐A, PIV‐3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections.

positive: Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing Abstract Background Coronavirus disease 2019 (COVID-19) is spreading. Here, we summarized the composition of pathogens in fever clinic patients and analyzed characteristics of different respiratory virus infection. Methods Retrospectively collected patients with definite etiological results using nasal and pharyngeal swabs in fever clinic. Results Totally, 1860 patients were screened and 136 patients were enrolled. 72 (52.94%) of them were diagnosed as influenza (Flu) A virus infection. 32 (23.53%) of them were diagnosed as Flu B virus infection. 18 (13.24%) and 14 (10.29%) of them were diagnosed as COVID-19 and respiratory syncytial virus (RSV) infection respectively. COVID-19 group had a higher rate of contact with epidemic area within 14 days and clustering onset than other groups. Fever was the most common symptom in these patients. The ratio of fever and the highest temperature were higher in Flu A virus infection patients than in COVID-19 patients. COVID-19 patients had lower white blood cell count and neutrophil count than Flu A virus and RSV infection group, but higher lymphocyte count than Flu A and B virus infection groups. COVID-19 group (83.33%) had higher rate of pneumonia in chest CT scan than Flu A and B virus infection groups. Conclusions Influenza viruses accounted for a large proportion of respiratory virus infection even during the epidemic of COVID-19 in Beijing. No single symptom or laboratory finding was suggestive of specific respiratory virus, however, epidemic history was important for screening of COVID-19.

positive: Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non‐respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10‐year time period (2003–2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not.

positive: COVID-19: Disease, management, treatment, and social impact Abstract COVID-19 was originated from Wuhan city of Hubei Province in China in December 2019. Since then it has spread in more than 210 countries and territories. It is a viral disease due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. The patients show flu-like symptoms with a dry cough, sore throat, high fever, and breathing problems. The disease due to SARS-CoV-2 was named as COVID-19. About 2.2 million people have been infected with more than 0.15 million deaths globally. The United States of America is the most affected country with the highest patients of about 0.7 million. Despite great efforts, there is no treatment of this disease. However, prevention and management are the best options. This article describes SARS-CoV-2, disease, prevention and management, treatment and social impact on society. It was analyzed that a combination of antiviral drugs with hydroxyl-chloroquine and azithromycin (with the consultation of a medical practitioner) may be the best option to treat the patients, depending on the patient's conditions and symptoms. However, Unani therapy may be useful along with allopathic treatment. It is urgently advised and requested that all the persons should follow the preventive measures, managements and quarantine strictly without any religious discrepancy otherwise the situation may be the worst. Also, there is an urgent requirement to educate our new generation for science and technology to fight against any such disaster in future; if any. There is no need to be panic and proper prevention and management are essential to combat this disease. This article may be useful to create awareness among the public, to prevent, manage and treat COVID-19.

positive: Convalescent plasma: possible therapy for novel coronavirus disease 2019

positive: Disparate temperature-dependent virus – host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium The human conductive respiratory tract spans a long anatomical distance and represents an important barrier to constrain invading respiratory pathogens. The disparate ambient temperatures found in the upper and lower respiratory tract have been demonstrated to influence the replication kinetics of common cold viruses as well as the associated host responses. Here, we employed the human airway epithelial cell (hAEC) culture model to investigate the impact of ambient temperatures found in the upper and lower respiratory tract, 33°C and 37°C, respectively, on the viral replication kinetics and host innate immune response dynamics during SARS-CoV-2 and SARS-CoV infections. Strikingly, SARS-CoV-2, in contrast to SARS-CoV, replicated more efficiently at temperatures encountered in the upper respiratory tract, and displayed higher sensitivity to type I and type III IFNs than SARS-CoV. Time-resolved transcriptome analysis highlighted a temperature-dependent induction of IFN-mediated antiviral response, whose amplitude inversely correlated with the replication kinetic efficiencies of both SARS-CoV-2 and SARS-CoV at temperatures found in the upper and lower respiratory tract. Altogether, these data reflect clinical features of SARS-CoV-2 and SARS-CoV and subsequently, their associated human-to-human transmission efficiencies. They provide crucial insights of the profound impact of ambient temperatures on viral replication and associated pivotal virus - host interaction dynamics. This knowledge can be exploited for the development of novel intervention strategies against SARS-CoV-2.

positive: Pollen likely seasonal factor in inhibiting flu-like epidemics. A Dutch study into the inverse relation between pollen counts, hay fever and flu-like incidence 2016-2019 There is uncertainty if current models for the Covid-19 pandemic should already take into account seasonality. That is because current environmental factors do not provide a powerful explanation of such seasonality, especially given climate differences between countries with moderate climates. It is hypothesized that one major factor is overlooked: pollen count. Pollen are documented to invoke strong immune responses and might create an environmental factor that makes it more difficult for flu-like viruses to survive outside a host. This Dutch study confirms that there is a (highly) significant inverse correlation between pollen count and weekly changes in medical flu consults, and that there is a highly significant inverse correlation between hay fever incidence, as measured by prescribed medication revenues, and weekly flu consults. This supports the idea that pollen are a direct or indirect factor in the seasonality of flu-like epidemics. If seasonality will be observed during the covid-19 spread as well, it is not unlikely that pollen play a role.

positive: Comparison of Hospitalized Patients with pneumonia caused by COVID-19 and influenza A in children under 5 years BACKGROUND: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to differentiate COVID-19 from other respiratory infectious diseases, such as influenza viruses. METHODS: This was a retrospective study. Two group of COVID-19 patients (n=57) and influenza A patients (n=59) were enrolled. We analyzed and compared their clinical manifestations, imaging characteristics and treatments. RESULTS: The proportions of cough (70.2%), fever (54.4%) and gastrointestinal symptoms (14.1%) in COVID-19 patients were lower than those of influenza A patients (98.3%, P<0.001; 84.7%, P<0.001; and 35.6%, P=0.007; respectively). In addition, COVID-19 patients showed significantly lower levels of leukocytes (7.87 vs. 9.89×109/L, P=0.027), neutrophils (2.43 vs. 5.16×109/L, P<0.001), C-reactive protein (CRP; 3.7 vs. 15.1mg/L, P=0.001) and procalcitonin (PCT; 0.09 vs. 0.68mm/h, P<0.001), while lymphocyte levels (4.58 vs. 3.56×109/L; P=0.006) were significantly higher compared with influenza A patients. In terms of CT imaging, ground-glass opacification in chest CT was more common in COVID-19 patients than in influenza A patients (42.1% vs. 15%, P=0.032). In contrast, consolidation was more common in influenza A patients (25%) than that in COVID-19 patients (5.2%, P=0.025). CONCLUSION: The clinical manifestations and laboratory tests of COVID-19 children are milder than those of influenza A children under 5 years. Additionally, imaging results more commonly presented as ground-glass opacities in COVID-19 patients.

positive: A Novel Methodology for Epidemic Risk Assessment: the case of COVID-19 outbreak in Italy We propose a novel data-driven framework for assessing the a-priori epidemic risk of a geographical area and for identifying high-risk areas within a country. Our risk index is evaluated as a function of three different components: the hazard of the disease, the exposure of the area and the vulnerability of its inhabitants. As an application, we discuss the case of COVID-19 outbreak in Italy. We characterize each of the twenty Italian regions by using available historical data on air pollution, human mobility, winter temperature, housing concentration, health care density, population size and age. We find that the epidemic risk is higher in some of the Northern regions with respect to Central and Southern Italy. The corresponding risk index shows correlations with the available official data on the number of infected individuals, patients in intensive care and deceased patients, and can help explaining why regions such as Lombardia, Emilia-Romagna, Piemonte and Veneto have suffered much more than the rest of the country. Although the COVID-19 outbreak started in both North (Lombardia and Veneto) and Central Italy (Lazio) almost at the same time, when the first cases were officially certified at the beginning of 2020, the disease has spread faster and with heavier consequences in regions with higher epidemic risk. Our framework can be extended and tested on other epidemic data, such as those on seasonal flu, and applied to other countries. We also present a policy model connected with our methodology, which helps policy-makers to take informed decisions.

positive: A prospective comparison of the epidemiological and clinical characteristics of pandemic (H1N1) 2009 influenza A virus and seasonal influenza A viruses in Guangzhou, South China in 2009. Comparisons of the clinical characteristics of contemporaneous pandemic (H1N1) 2009 influenza A virus (A(H1N1)pdm09)- and seasonal influenza viruses-infected patients are important for both clinical management and epidemiological studies. A prospective multicenter observational study was conducted using a preestablished sentinel surveillance system in Guangzhou, China during 2009. In this study, the clinical presentations of patients with either acute respiratory infection or community-acquired pneumonia were recorded, and nasopharyngeal swab samples were collected for detection of respiratory virus strains using cell cultures or real-time reverse transcription/real-time polymerase chain reaction. Comparisons of the clinical features between A(H1N1)pdm09- and seasonal influenza viruses-infected patients were conducted accordingly. Of the 1,498 patients examined, 265 tested positive for A(H1N1)pdm09, 286 were positive for seasonal influenza A viruses, and 137 for influenza B viruses. The predominant virus was influenza B before the emergence of A(H1N1)pdm09 (epidemiological week [EW] 1-EW 21); then, predominantly non-A(H1N1)pdm09 influenza A and, later, A(H1N1)pdm09, which peaked in EW 46. Compared with the common seasonal influenza-infected patients, A(H1N1)pdm09-infected patients were younger, and had a higher proportion of these patients reported prior contact with infected individuals (P < 0.001, by χ(2) test). However, few significant differences were observed in clinical symptoms and severity among any of the infections caused by the different influenza A strains. Our hospital-based network served as a useful source of information during A(H1N1)pdm09 monitoring. Viral distribution in Guangzhou was characterized by a sharp rise in A(H1N1)pdm09-infected patients in September 2009. Similar to seasonal influenza A-infected cases, A(H1N1)pdm09 cases had a very small proportion of severe cases.

positive: Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. METHODS: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. FINDINGS: SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. INTERPRETATION: The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. FUNDING: US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.

positive: [Detection of respiratory viruses in influenza-like illness in Shijiazhuang, China in 2011]. This study aimed to investigate viral infections and the prevalence of influenza-like illness (ILI) in Shijiazhuang, China, in 2011 and to provide a scientific basis for the diagnosis and control of respiratory tract infections. Throat swab specimens were collected from 483 cases of ILI who were outpatients in the influenza surveillance sentinel hospitals in Shijiazhuang between January and December 2011. All specimens were examined by multiplex RT-PCR for the following 15 respiratory tract viruses: adenovirus (ADV), human rhinovirus (HRV), human parainfluenza virus (PIV types 1-4), influenza virus A (FluA), influenza virus B (FluB), human enterovirus (HEV), respiratory syncytial virus (RSV-A and -B), human metapneumovirus (HMPV), human coronavirus (HCoV-229E/NL63 and -OC43/HKU1), and human bocavirus (HBoV). Among the 483 cases of ILI, 214 (44.31%) were positive for viruses, including ADV (8.7%), HEV (8.7%), RSV-A (8.07%), HRV (7.45%), FluA (5.38%), HCoV-OC43/ HKU1 (2.9%), PIV-3 (2.9%), HMPV (1.86%), PIV-1 (1.24%), HCoV-229E/NL63 (1.04%), PIV-2 (1.04%), HBoV (0.83%), and FluB (0.41%). Twenty-six (5.38%) of all cases were co-infected with two or more viruses, most commonly HEV/HRV with other viruses. Cases of viral infection were detected throughout the year, with peaks in January and February. ADV and HRV were detected throughout almost the whole year without obvious seasonality. HEV was detected between April and November, with a peak of prevalence in summer and autumn. FluA and FluB reached epidemic levels mainly in winter and spring. All cases of RSV were identified to be subtype A. PIV infection was mainly caused by PIV-3. The positive rate of HCoV-OC43/HKU1 infection was significantly higher than that of HCoV-229E/NL63. The leading five viruses that resulted in ILI Shijiazhuang in 2011 were HEV, ADV, RSV-A, HRV, and FluA, and these viruses have different epidemiological features.

positive: The 2019 coronavirus: Learning curves, lessons, and the weakest link In the space of just six weeks, a new coronavirus, from a family that historically was not viewed as a global health concern, has become daily headline news around the globe. The 21st century marked its arrival with the emergence of three previously unknown coronaviruses. SARS-CoV (severe acute respiratory syndrome coronavirus) was recognized in November 2002 [1, 2], MERS-CoV (Middle East respiratory syndrome coronavirus) in June 2012 [3, 4], and 2019-nCoV in December 2019 [5]. Previously, human coronaviruses, known since the 1960s, were viewed as being only marginally relevant to the clinic, except for infants, the elderly, and immunocompromised individuals [1, 6, 7].

positive: Genetic and antigenic characterization of influenza A(H3N2) in Cameroon during the 2014-2016 influenza seasons The first outbreak of influenza A(H3N2) occurred in 1968 and caused the third flu pandemic of the 20(th) century. It has affected multiple countries over time. The best strategy to reduce the burden of influenza is through vaccination whose efficacy varies with respect to the circulating strains. This study was performed to better understand the molecular evolution of influenza A(H3N2) and assess vaccine efficacy in Cameroon. Complete sequences of three gene segments were obtained from 2014 to 2016 influenza seasons in Cameroon. Hemagglutinin (HA), Neuraminidase (NA) and matrix (M) genes of 35 A(H3N2) virus strains were amplified and sequenced. Predicted vaccine efficacy was measured using the P(epitope) model. Phylogenetic analysis of the HA gene showed that all Cameroonian strains had evolved away from the 3C.1-A/Texas/50/2012-like clade. Globally, 2014 virus strains clustered with the 2015–2016 vaccine strain, 3C.3a-A/Switzerland/9715293/2013, whereas 2015 and 2016 virus strains clustered with the 2016–2017 vaccine strain, 3C.2a-A/HongKong/4801/2014. In order to determine the genotypic drug susceptibility to neuraminidase inhibitors and amantadine, the NA and M2 protein coding sequences were analyzed. There was no strain with characteristic mutation for resistance to neuraminidase inhibitors, per contra; all strains possessed the substitution S31N, peculiar of resistance to adamantanes. There was drift in influenza A(H3N2) dominant epitopes B (2014 and 2015) to epitopes A (2016) with a theoretical efficiency in vaccine ranging from low to moderate. The presence of several antigenic site mutations among H3N2 virus strains between 2014–2016 influenza seasons in Cameroon confirms the progressing evolution of circulating H3N2 strains.

positive: A global treatments for coronaviruses including COVID‐19 In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019‐nCoV). So far, there are no specific treatments for patients with coronavirus disease‐19 (COVID‐19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome‐related coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID‐19. Cathepsin L is required for entry of the 2019‐nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin‐converting‐enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID‐19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019‐nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS‐CoV disease and can be useful for patients of COVID‐19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS‐CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS‐CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID‐19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.

positive: Etiology and Clinical Characterization of Respiratory Virus Infections in Adult Patients Attending an Emergency Department in Beijing BACKGROUND: Acute respiratory tract infections (ARTIs) represent a serious global health burden. To date, few reports have addressed the prevalence of respiratory viruses (RVs) in adults with ARTIs attending an emergency department (ED). Therefore, the potential impact of respiratory virus infections on such patients remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine the epidemiological and clinical profiles of common and recently discovered respiratory viruses in adults with ARTIs attending an ED in Beijing, a 1-year consecutive study was conducted from May, 2010, to April, 2011. Nose and throat swab samples from 416 ARTI patients were checked for 13 respiratory viruses using multiple reverse transcription polymerase chain reaction(RT-PCR) assays for common respiratory viruses, including influenza viruses (Flu) A, B, and adenoviruses (ADVs), picornaviruses (PICs), respiratory syncytial virus (RSV), parainfluenza viruses (PIVs) 1–3, combined with real-time RT-PCR for human metapneumovirus (HMPV) and human coronaviruses (HCoVs, -OC43, -229E, -NL63, and -HKU1). Viral pathogens were detected in 52.88% (220/416) of patient samples, and 7.21% (30/416) of patients tested positive for more than one virus. PICs (17.79%) were the dominant agents detected, followed by FluA (16.11%), HCoVs (11.78%), and ADV (11.30%). HMPV, PIVs, and FluB were also detected (<3%), but not RSV. The total prevalence and the dominant virus infections detected differed significantly between ours and a previous report. Co-infection rates were high for HCoV-229E (12/39, 30.76%), PIC (22/74, 29.73%), ADV (12/47, 25.53%) and FluA (15/67, 22.39%). Different patterns of clinical symptoms were associated with different respiratory viruses. CONCLUSIONS: The pattern of RV involvement in adults with ARTIs attending an ED in China differs from that previously reported. The high prevalence of viruses (PIC, FluA, HCoVs and ADV) reported here strongly highlight the need for the development of safe and effective therapeutic approaches for these viruses.

positive: Role of temperature and humidity in the modulation of the doubling time of COVID-19 cases COVID-19 is having a great impact on public health, mortality and economy worldwide, in spite of the efforts to prevent its epidemy. The SARS-CoV-2 genome is different from that of MERS-CoV and SARS-CoV, although also expected to spread differently according to meteorological conditions. Our main goal is to investigate the role of some meteorological variables on the expansion of this outbreak. In this study, an exponential model relating the number of accumulated confirmed cases and time was considered. The rate of COVID-19 spread, using as criterion the doubling time of the number of confirmed cases, was used as dependent variable in a linear model that took four independent meteorological variables: temperature, humidity, precipitation and wind speed. Only China cases were considered, to control both cultural aspects and containment policies. Confirmed cases and the 4 meteorological variables were gathered between January 23 and March 1 (39 days) for the 31 provinces of Mainland China. Several periods of time were sampled for each province, obtaining more than one value for the rate of disease progression. Two different periods of time were tested, of 12 and 15 days, along with 3 and 5 different starting points in time, randomly chosen. The median value for each meteorological variable was computed, using the same time period; models with adjusted R square above 0.75 were selected. The rate of progression and doubling time were computed and used to fit a linear regression model. Models were evaluated using alpha=0.05. Results indicate that the doubling time correlates positively with temperature and inversely with humidity, suggesting that a decrease in the rate of progression of COVID-19 with the arrival of spring and summer in the north hemisphere. A 20oC increase is expected to delay the doubling time in 1.8 days. Those variables explain 18% of the variation in disease doubling time; the remaining 82% may be related to containment measures, general health policies, population density, transportation or cultural aspects.

positive: Could Environment Affect the Mutation of H1N1 Influenza Virus? H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000–2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors.

positive: Increasing similarity in the dynamics of influenza in two adjacent subtropical Chinese cities following the relaxation of border restrictions. The drivers of influenza seasonality remain heavily debated, especially in tropical/subtropical regions where influenza activity can peak in winter, during the rainy season, or remain constant throughout the year. We compared the epidemiological and evolutionary patterns of seasonal influenza epidemics in Hong Kong and Shenzhen, two adjacent cities in subtropical southern China. This comparison represents a unique natural experiment, as connectivity between these two cities has increased over the past decade. We found that, whilst summer influenza epidemics in Shenzhen used to peak 1-3 months later than those in Hong Kong, the difference decreased after 2005 (P<0.0001). Phylogenetic analysis revealed that influenza isolates from Shenzhen have become genetically closer to those circulating in Hong Kong over time (P = 0.045). Furthermore, although Shenzhen isolates used to be more distant from the global putative source of influenza viruses than isolates from Hong Kong (P<0.001), this difference has narrowed (P = 0.02). Overall, our study reveals that influenza activities show remarkably distinct epidemiological and evolutionary patterns in adjacent subtropical cities and suggests that human mobility patterns can play a major role in influenza dynamics in the subtropics.

positive: Co-infection with SARS-CoV-2 and influenza A virus Coronavirus Disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is spreading globally and poses a major public health threat. We reported a case of influenza A virus and SARS-CoV-2 co-infection. As the number of COVID-19 cases increase, it will be necessary to comprehensively evaluate imaging and other clinical findings as well as consider co-infection with other respiratory viruses.

positive: Comparison of the clinical characteristics and outcomes of hospitalized adult COVID-19 and influenza patients: a prospective observational study Objective We compared the clinical characteristics, findings and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences. Methods From December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at the HUS Jorvi Hospital, Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for at least 30 days from admission. Results We included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs 67%) and had at least one comorbidity (68% vs 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs 15 [45%], P=0.03 and 1 [4%] vs 10 [30%], P=0.008). In chest x-ray at admission, ground-glass opacities and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], P < 0.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs 19 [58%], P=0.003 and 8 [29%] vs 2 [6%], P=0.034). COVID-19 patients were hospitalized longer than influenza patients (6 days [IQR 4-21] vs 3 [2-4], P<0.001). Conclusion Bilateral ground-glass opacities and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.

positive: Coronavirus Disease 2019 (COVID-19): Clinical Perspectives and Ongoing Challenges BACKGROUND: Emerging infectious diseases pose a great hazard to public health and the global economy A novel coronavirus, SARS-CoV-2, causing coronavirus disease 2019 (COVID-19), emerged from Wuhan, China, in December 2019 Since then, it has spread globally causing a global health emergency of inconceivable magnitude, with significant morbidity and mortality There is the need for clinicians and health care providers to understand and gain knowledge of the different aspects of the disease as it evolves OBJECTIVE: We reviewed existing literature on COVID-19 in order to present a synopsis of current understanding of the disease METHODS: Using PubMed, Embase and Medline, articles published between January and April 2020 on Coronavirus disease 2019 (COVID-19), and resources from World Health Organisation were analyzed in order to have an understanding of the clinical characteristics, transmission dynamics, virology, diagnostic possibilities, prevention, management approach, controversies and impact of COVID-19 on the healthcare workforce RESULTS: Our review revealed that COVID-19 patients present with a myriad of symptoms, ranging from mild to severe respiratory disease, which can often be fatal The mode of transmission via droplet infections makes it unduly contagious and difficult to control Currently, antiviral drugs or vaccines are being developed to manage this condition CONCLUSION: There is urgent need for potent antivirals and vaccine to manage those infected with COVID 19 and prevent infection Global efforts need to be unified in combating this public health emergency and flattening the curve of spread

positive: The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention. One sentence summary The novel 2019 coronavirus and the SARS-coronavirus share central biological properties which can guide risk assessment and intervention.

positive: Emerging and reemerging respiratory viral infections up to Covid-19 Infectious diseases remain as the significant causes of human and animal morbidity and mortality, leading to extensive outbreaks and epidemics. Acute respiratory viral diseases claim over 4 million deaths and cause millions of hospitalizations in developing countries every year. Emerging viruses, especially the RNA viruses, are more pathogenic since most people have no herd immunity. The RNA viruses can adapt to the rapidly changing global and local environment due to the high error rate of their polymerases that replicate their genomes. Currently, coronavirus disease 2019 (COVID-19) is determined as an u28a9 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in 2019 in u28ac. Herein we discuss emerging and reemerging respiratory viral infections till to SARS-CoV-2.

positive: Echoes of 2009 H1N1 Influenza Pandemic in the COVID Pandemic Abstract The severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV2) pandemic that has engulfed the globe has had incredible effects on health care systems and economic activity. Social distancing and school closures have played a central role in public health efforts to counter the coronavirus disease 2019 (COVID)-19 pandemic. The most recent global pandemic prior to COVID-19 was the 2009 pandemic, hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza. The course of events in 2009 offer some rich lessons that could be applied to the current COVID-19 pandemic. This commentary highlights some of the most relevant points and a discussion of possible outcomes of the COVID-19 pandemic. © 2020 Elsevier Inc.

positive: COVID-19: A promising cure for the global panic Abstract The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.

positive: Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

positive: Environmental concern regarding the effect of humidity and temperature on 2019-nCoV survival: fact or fiction The new coronavirus, called 2019-nCoV, is a new type of virus that was first identified in Wuhan, China, in December 2019. Environmental conditions necessary for survival and spread of 2019-nCoV are somewhat transparent but unlike animal coronaviruses. We are poorly aware of their survival in environment and precise factors of their transmission. Countries located in east and west of globe did not have a significant impact on prevalence of disease among communities, and on the other hand, north and south have provided a model for relative prediction of disease outbreaks. The 2019-nCoV can survive for up to 9 days at 25 °C, and if this temperature rises to 30 °C, its lifespan will be shorter. The 2019-nCoV is sensitive to humidity, and lifespan of viruses in 50% humidity is longer than that of 30%. Also, temperature and humidity are important factors influencing the COVID-19 mortality rate and may facilitate 2019-nCoV transmission. Thus, considering the available and recent evidence, it seems that low temperatures, as well as dry and unventilated air, may affect stability and transmissibility of 2019-nCoV.

positive: The epidemiological and clinical features of COVID-19 and lessons from this global infectious public health event Abstract Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease of great global public health importance. As of March 26, 2020, the outbreak of COVID-19 has resulted in 462,801 confirmed cases and 20,839 deaths globally, which is more than those caused by SARS and Middle East respiratory syndrome (MERS) in 2003 and 2013, respectively. The epidemic has posed considerable challenges worldwide. Under a strict mechanism of massive prevention and control, China has seen a rapid decrease in new cases of coronavirus; however, the global situation remains serious. Additionally, the origin of COVID-19 has not been determined and no specific antiviral treatment or vaccine is currently available. Based on the published data, this review systematically discusses the etiology, epidemiology, clinical characteristics, and current intervention measures related to COVID-19 in the hope that it may provide a reference for future studies and aid in the prevention and control of the COVID-19 epidemic.

positive: Future Perspectives of Wastewater-Based Epidemiology: Monitoring Infectious Disease Spread and Resistance to the Community Level Abstract Infectious diseases are acknowledged as one of the most critical threats to global public health today. Climate change, unprecedented population growth with accelerated rates of antimicrobial resistance, have resulted in both the emergence of novel pathogenic organisms and the re-emergence of infections that were once controlled. The consequences have led to an increased vulnerability to infectious diseases globally. The ability to rapidly monitor the spread of diseases is key for prevention, intervention and control, however several limitations exist for current surveillance systems and the capacity to cope with the rapid population growth and environmental changes. Wastewater-Based Epidemiology (WBE) is a new epidemiology tool that has potential to act as a complementary approach for current infectious disease surveillance systems and an early warning system for disease outbreaks. WBE postulates that through the analysis of population pooled wastewater, infectious disease and resistance spread, the emergence of new disease outbreak to the community level can be monitored comprehensively and in real-time. This manuscript provides critical overview of current infectious disease surveillance status, as well as it introduces WBE and its recent advancements. It also provides recommendations for further development required for WBE application as an effective tool for infectious disease surveillance.

positive: Global COVID-19 transmission rate is influenced by precipitation seasonality and the speed of climate temperature warming The novel coronavirus disease 2019 (COVID-19) became a rapidly spreading worldwide epidemic; thus, it is a global priority to reduce the speed of the epidemic spreading. Several studies predicted that high temperature and humidity could reduce COVID-19 transmission. However, exceptions exist to this observation, further thorough examinations are thus needed for their confirmation. In this study, therefore, we used a global dataset of COVID-19 cases and global climate databases and comprehensively investigated how climate parameters could contribute to the growth rate of COVID-19 cases while statistically controlling for potential confounding effects using spatial analysis. We also confirmed that the growth rate decreased with the temperature; however, the growth rate was affected by precipitation seasonality and warming velocity rather than temperature. In particular, a lower growth rate was observed for a higher precipitation seasonality and lower warming velocity. These effects were independent of population density, human life quality, and travel restrictions. The results indicate that the temperature effect is less important compared to these intrinsic climate characteristics, which might thus be useful for explaining the exceptions. However, the contributions of the climate parameters to the growth rate were moderate; rather, the contribution of travel restrictions in each country was more significant. Although our findings are preliminary owing to data-analysis limitations, they may be helpful when predicting COVID-19 transmission.

positive: Does this patient have COVID-19? A practical guide for the internist Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its ‘semeiotic’. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.

positive: This really is nothing like flu Those downplaying the coronavirus ignore our lack of immunity and vaccines

positive: Laboratory Detection of Respiratory Viruses by Automated Techniques Advances in clinical virology for detecting respiratory viruses have been focused on nucleic acids amplification techniques, which have converted in the reference method for the diagnosis of acute respiratory infections of viral aetiology. Improvements of current commercial molecular assays to reduce hands-on-time rely on two strategies, a stepwise automation (semi-automation) and the complete automation of the whole procedure. Contributions to the former strategy have been the use of automated nucleic acids extractors, multiplex PCR, real-time PCR and/or DNA arrays for detection of amplicons. Commercial fully-automated molecular systems are now available for the detection of respiratory viruses. Some of them could convert in point-of-care methods substituting antigen tests for detection of respiratory syncytial virus and influenza A and B viruses. This article describes laboratory methods for detection of respiratory viruses. A cost-effective and rational diagnostic algorithm is proposed, considering technical aspects of the available assays, infrastructure possibilities of each laboratory and clinic-epidemiologic factors of the infection

positive: Comparative seasonalities of influenza A, B and ‘common cold’ coronaviruses – setting the scene for SARSCoV-2 infections and possible unexpected host immune interactions

positive: A novel coronavirus outbreak of global health concern

positive: In-host Modelling of COVID-19 Kinetics in Humans COVID-19 pandemic has underlined the impact of emergent pathogens as a major threat for human health. The development of quantitative approaches to advance comprehension of the current outbreak is urgently needed to tackle this severe disease. In this work, several mathematical models are proposed to represent COVID-19 dynamics in infected patients. Considering different starting times of infection, parameters sets that represent infectivity of COVID-19 are computed and compared with other viral infections that can also cause pandemics. Based on the target cell model, COVID-19 infecting time between susceptible cells (mean of 30 days approximately) is much slower than those reported for Ebola (about 3 times slower) and influenza (60 times slower). The within-host reproductive number for COVID-19 is consistent to the values of influenza infection (1.7-5.35). The best model to fit the data was including immune responses, which suggest a slow cell response peaking between 5 to 10 days post onset of symptoms. The model with eclipse phase, time in a latent phase before becoming productively infected cells, was not supported. Interestingly, both, the target cell model and the model with immune responses, predict that virus may replicate very slowly in the first days after infection, and it could be below detection levels during the first 4 days post infection. A quantitative comprehension of COVID-19 dynamics and the estimation of standard parameters of viral infections is the key contribution of this pioneering work.

positive: Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19) IMPORTANCE: Coronavirus disease 2019 (COVID-19) infection has resulted in a global crisis. Investigating the potential association of climate and seasonality with the spread of this infection could aid in preventive and surveillance strategies. OBJECTIVE: To examine the association of climate with the spread of COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined climate data from 50 cities worldwide with and without substantial community spread of COVID-19. Eight cities with substantial spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) were compared with 42 cities that have not been affected or did not have substantial community spread. Data were collected from January to March 10, 2020. MAIN OUTCOMES AND MEASURES: Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020. Climate data (latitude, mean 2-m temperature, mean specific humidity, and mean relative humidity) were obtained from ERA-5 reanalysis. RESULTS: The 8 cities with substantial community spread as of March 10, 2020, were located on a narrow band, roughly on the 30° N to 50° N corridor. They had consistently similar weather patterns, consisting of mean temperatures of between 5 and 11 °C, combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m(3)). There was a lack of substantial community establishment in expected locations based on proximity. For example, while Wuhan, China (30.8° N) had 3136 deaths and 80 757 cases, Moscow, Russia (56.0° N), had 0 deaths and 10 cases and Hanoi, Vietnam (21.2° N), had 0 deaths and 31 cases. CONCLUSIONS AND RELEVANCE: In this study, the distribution of substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements was consistent with the behavior of a seasonal respiratory virus. Using weather modeling, it may be possible to estimate the regions most likely to be at a higher risk of substantial community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.

positive: Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics The objective of this Personal View is to compare transmissibility, hospitalisation, and mortality rates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with those of other epidemic coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and pandemic influenza viruses. The basic reproductive rate (R(0)) for SARS-CoV-2 is estimated to be 2·5 (range 1·8–3·6) compared with 2·0–3·0 for SARS-CoV and the 1918 influenza pandemic, 0·9 for MERS-CoV, and 1·5 for the 2009 influenza pandemic. SARS-CoV-2 causes mild or asymptomatic disease in most cases; however, severe to critical illness occurs in a small proportion of infected individuals, with the highest rate seen in people older than 70 years. The measured case fatality rate varies between countries, probably because of differences in testing strategies. Population-based mortality estimates vary widely across Europe, ranging from zero to high. Numbers from the first affected region in Italy, Lombardy, show an all age mortality rate of 154 per 100 000 population. Differences are most likely due to varying demographic structures, among other factors. However, this new virus has a focal dissemination; therefore, some areas have a higher disease burden and are affected more than others for reasons that are still not understood. Nevertheless, early introduction of strict physical distancing and hygiene measures have proven effective in sharply reducing R(0) and associated mortality and could in part explain the geographical differences.

positive: INFECTIONS IN PREGNANCY WITH COVID-19 AND OTHER RESPIRATORY RNA VIRUS DISEASES ARE RARELY, IF EVER, TRANSMITTED TO THE FETUS: EXPERIENCES WITH CORONAVIRUSES, HPIV, hMPV RSV, AND INFLUENZA SARS-CoV-2, the agent of COVID-19, is similar to two other coronaviruses, SARS-CoV and MERS-CoV, in causing life-threatening maternal respiratory infections and systemic complications. Because of global concern for potential intrauterine transmission of SARS-CoV-2 from pregnant women to their infants, this report analyzes the effects on pregnancy of infections caused by SARS-CoV-2 and other respiratory RNA viruses, and examines the frequency of maternal-fetal transmission with SARS-CoV-2, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, respiratory syncytial virus (RSV), parainfluenza (HPIV) and metapneumovirus (hMPV). There have been no confirmed cases of intrauterine transmission reported with COVID-19 or any other coronavirus infections. Influenza virus, despite causing approximately one billion annual infections globally, has only a few cases of confirmed or suspected intrauterine fetal infections reported. RSV is in an unusual cause of illness among pregnant women, and with the exception of one premature infant with congenital pneumonia, no other cases of maternal-fetal infection are described. Parainfluenza virus and human metapneumovirus can produce symptomatic maternal infections but do not cause intrauterine fetal infection. In summary, it appears that the absence thus far of maternal-fetal transmission of the SARS-CoV-2 virus during the COVID-19 pandemic is similar to other coronaviruses, and is also consistent with the extreme rarity of suggested or confirmed cases of intrauterine transmission of other respiratory RNA viruses. This observation has important consequences for pregnant women as it appears that if intrauterine transmission of SARSCoV-2 does eventually occur, it will be a rare event. Potential mechanisms of fetal protection from maternal viral infections are also discussed.

positive: Influenza as a model system for studying the cross-species transfer and evolution of the SARS coronavirus. Severe acute respiratory syndrome coronavirus (SARS-CoV) moved into humans from a reservoir species and subsequently caused an epidemic in its new host. We know little about the processes that allowed the cross-species transfer of this previously unknown virus. I discuss what we have learned about the movement of viruses into humans from studies of influenza A, both how it crossed from birds to humans and how it subsequently evolved within the human population. Starting with a brief review of severe acute respiratory syndrome to highlight the kinds of problems we face in learning about this viral disease, I then turn to influenza A, focusing on three topics. First, I present a reanalysis of data used to test the hypothesis that swine served as a "mixing vessel" or intermediate host in the transmission of avian influenza to humans during the 1918 "Spanish flu" pandemic. Second, I review studies of archived viruses from the three recent influenza pandemics. Third, I discuss current limitations in using molecular data to study the evolution of infectious disease. Although influenza A and SARS-CoV differ in many ways, our knowledge of influenza A may provide important clues about what limits or favours cross-species transfers and subsequent epidemics of newly emerging pathogens.

positive: Mathematical modeling of interaction between innate and adaptive immune responses in COVID-19 and implications for viral pathogenesis We have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease-2019 (COVID-19) pandemic caused by SARS-CoV-2 virus. We first validated our model using the well-studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID-19 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. The adaptive immune response of the COVID-19 patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID-19 patients while enhancing viral clearance in influenza patients. Stronger adaptive immunity in COVID-19 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high-risk COVID-19 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.

positive: Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.

positive: Coronavirus occurrence and transmission over 8 years in the HIVE cohort of households in Michigan BACKGROUND: As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults over 8 years. METHODS: Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. RESULTS: In total, 993 HCoV infections were identified over 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May, and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range: 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. CONCLUSIONS: Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.

positive: Intervention strategies for emerging respiratory virus infections: policy and public health considerations Respiratory viruses have emerged and re-emerged in humans for hundreds of years. In the recent past avian and animal influenza viruses have caused human disease ranging from conjunctivitis to respiratory illnesses, including the 2009–10 A(H1N1)pdm09 pandemic. Coronaviruses, human metapneumovirus (hMPV) and enteroviruses have also impacted humans globally. Since the likely public health impacts are common, plans and policies for intervention strategies can be developed, encompassing early detection through surveillance and diagnostics, as well as treatment and prevention through clinical and non-clinical interventions. The global comprehensiveness of these varies according to differing resources, competing health priorities and the causative agent, yet, irrespective of this, activities must be proportional to the threat. Pandemics and severe epidemics enable policies to be tested and gaps identified.

positive: How Should the Rehabilitation Community Prepare for 2019-nCoV? Abstract With the 2019-nCoV pandemic spreading quickly in USA and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so the majority of world’s population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it are currently mainly social distancing and infection control measures.

positive: Are We Ready for Coronavirus Disease 2019 Arriving at Schools?

positive: Changes in blood coagulation in patients with severe coronavirus disease 2019 (COVID‐19): a meta‐analysis Coronavirus disease 2019 (COVID-19) is widely spread and poses a critical threat to global health (Zhang et al). Prominent changes in coagulation function in severe patients of COVID-19 have been reported in a recent study (Han, et al 2020). Therefore, we conducted this quantitative meta-analysis to explore the difference in blood coagulation parameters between severe and mild cases of COVID-19.

positive: Target Virus or Target Ourselves for COVID-19 Drugs Discovery?-Lessons learned from anti-influenzas virus therapies Abstract The COVID-19 pandemic, after it was reported in December 2019, is a highly contagious and now spreading to over 190 countries, causing a severe public health burden. Currently, there is no vaccine or specific drug to treat COVID-19, which is caused by a novel coronavirus, SARS-2-CoV. For this emergency, the FDA has approved Remdesivir and Hydroxychloroquine for treatment of COVID-19 as Emergency Use Authorization. However, even after this pandemic, COVID-19 may still have a chance to come back. Therefore, we need to come out with new strategies for drug discovery for combating COVID-19 in the future.

positive: A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19) Coronavirus disease 2019 (COVID-19) is a declared global pandemic. There are multiple parameters of the clinical course and management of the COVID-19 that need optimization. A hindrance to this development is the vast amount of misinformation present due to scarcely sourced manuscript preprints and social media. This literature review aims to presents accredited and the most current studies pertaining to the basic sciences of SARS-CoV-2, clinical presentation and disease course of COVID-19, public health interventions, and current epidemiological developments. The review on basic sciences aims to clarify the jargon in virology, describe the virion structure of SARS-CoV-2 and present pertinent details relevant to clinical practice. Another component discussed is the brief history on the series of experiments used to explore the origins and evolution of the phylogeny of the viral genome of SARS-CoV-2. Additionally, the clinical and epidemiological differences between COVID-19 and other infections causing outbreaks (SARS, MERS, H1N1) are elucidated. Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. These can be used to triage and expedite risk assessment. Furthermore, the limitations and statistical strength of the diagnostic tools currently in clinical practice are evaluated. Criteria on rapid screening, discharge from hospital and discontinuation of self-quarantine are clarified. Epidemiological factors influencing the rapid rate of spread of the SARS-CoV-2 virus are described. Accurate information pertinent to improving prevention strategies is also discussed. The penultimate portion of the review aims to explain the involvement of micronutrients such as vitamin C and vitamin D in COVID19 treatment and prophylaxis. Furthermore, the biochemistry of the major candidates for novel therapies is briefly reviewed and a summary of their current status in the clinical trials is presented. Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed. The composite collection of accredited studies on each of these subtopics of COVID-19 within this review will enable clarification and focus on the current status and direction in the planning of the management of this global pandemic.

positive: Coronavirus Disease 2019 (COVID-19) and healthcare-associated infections: Emerging and future challenges for public health in Brazil

positive: Coronavirus Epidemic and Extracorporeal Therapies in Intensive Care: si vis pacem para bellum

positive: Can Search Query Forecast successfully in China's 2019-nCov pneumonia? Recently the novel coronavirus (2019-nCov) pneumonia outbreak in China then the world, and the Number of infections and death continues to increases. Search Query performs well in forecasting the epidemics. It is still a question whether search engine data can forecast the drift and the inflexion in 2019-nCov pneumonia. Based on the Baidu Search Index, we propose three prediction models: composite Index, composite Index with filtering and suspected NCP(Novel Coronavirus Pneumonia). The result demonstrates that the predictive model of composite index with filtering performs the best while the model of suspected NCP has the highest forecast error. We further predict the out-of-the-set NCP confirmed cases and monitor that the next peak of new diagnoses will occur on February 16th and 17th.

positive: Co‐infection in SARS‐CoV‐2 infected Patients: Where Are Influenza Virus and Rhinovirus/Enterovirus? Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has been declared a global pandemic. Our goal was to determine whether coinfections with other respiratory pathogens occur in a significant subset of SARS‐CoV‐2 infected patients in the greater New York City metropolitan area. During the period from March 16, 2020 through April 20, 2020, our laboratory detected SARS‐CoV‐2 infection in 8,990 patients of a total 18,704 tested by real‐time reverse‐transcription‐polymerase‐chain‐reaction amplification (SARS‐CoV‐2 Test, cobas® 6800 system, RocheDiagnostics). Amongst the patients who tested positive for SARS‐CoV‐2, 1,204 were also tested for other respiratory viruses, and concurrent infection was found in only 36 (< 3%). In comparison, coinfection with at least one non‐SARS‐CoV‐2 respiratory viral pathogen was found in 13.1% of patients who tested negative for SARS‐CoV‐2. Additionally, in patients who tested negative for SARS‐CoV‐2, the most common respiratory virus co‐infections were those commonly seen circulating in the community including rhinovirus/enterovirus, influenza viruses and coronavirus NL63, whereas non‐SARS‐CoV‐2 coronaviridae were the most common concurrent respiratory viruses found in SARS‐CoV‐2 –positive patients. Additional studies are needed to establish whether simultaneous viral infection in SARS‐CoV‐2 patients could potential drive viral interference or influence disease outcomes. This article is protected by copyright. All rights reserved.

positive: Novel coronavirus 2019 (COVID‐19): Emergence and implications for emergency care A novel coronavirus (COVID‐19) causing acute illness with severe symptoms has been isolated in Wuhan, Hubei Province, China. Since its emergence, cases have been found worldwide, reminiscent of severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks over the past 2 decades. Current understanding of this epidemic remains limited due to its rapid development and available data. While occurrence outside mainland China remains low, the likelihood of increasing cases globally continues to rise. Given this potential, it is imperative that emergency clinicians understand the preliminary data behind the dynamics of this disease, recognize possible presentations of patients, and understand proposed treatment modalities.

positive: Comparison of viral and epidemiological profiles of hospitalized children with severe acute respiratory infection in Beijing and Shanghai, China BACKGROUND: No comparison data have been reported on viral and epidemiological profiles of hospitalized children with severe acute respiratory infection (SARI) in Beijing or Shanghai, China. METHODS: We collected 700 nasopharyngeal aspirates (NPA) from hospitalized children with SARI in Beijing (northern China) and Shanghai (southern China). Multiple respiratory viruses (including 15 common viruses) were screened by validated polymerase chain reaction (PCR) or real-time reverse transcription-PCR assays and confirmed by sequencing. Demographic data and the distribution of viral infections were also examined. RESULTS: Of 700 samples, 547 (78.1%) tested positive for viral infections. The picornaviruses (PIC), which included rhinovirus (RV) and enterovirus (EV), were the most common (34.0%), followed by respiratory syncytial virus (RSV) (28.3%), human bocavirus (HBoV) (19.1%), adenovirus (ADV) (13.7%), human coronaviruses (HCoV) (10.7%), influenza A and B (8.9%), parainfluenza virus (PIV 1–3) (7.9%), and human metapneumovirus (HMPV) (5.0%). PIC (RV/EV) and RSV were the most prevalent etiological agents of SARI in both cities. The total and age-matched prevalence of RSV, HCoV, and hMPV among SARI children under 5 years old were significantly higher in Beijing than in Shanghai. Different age and seasonal distribution patterns of the viral infections were found between Beijing and Shanghai. CONCLUSIONS: Viral infection was tested and shown to be the most prevalent etiological agent among children with SARI in either the Beijing or the Shanghai area, while showing different patterns of viral and epidemiological profiles. Our findings provide a better understanding of the roles of geographic location and climate in respiratory viral infections in hospitalized children with SARI.

positive: Effects of temperature and humidity on the spread of COVID-19: A systematic review. Background: Faced with the global pandemic of COVID-19, declared by World Health Organization (WHO) on March 11th 2020, and the need to better understand the seasonal behavior of the virus, our team conducted this systematic review to describe current knowledge about the emergence and replicability of the virus and its correlation with different weather factors such as temperature and relative humidity. Methods: The review was registered with the PROSPERO database. The electronic databases PubMed, Scopus, Web of Science, Cochrane Library, LILACS, OpenGrey and Google Scholar were examined with the searches restricted to the years 2019 and 2020. Risk of bias assessment was performed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist tool. The GRADE tool was used to assess the quality of the evidence. Results: The initial screening identified 517 articles. After examination of the full texts, seventeen studies met the review's eligibility criteria. Great homogeneity was observed in the findings regarding the effect of temperature and humidity on the seasonal viability and transmissibility of COVID-19. Cold and dry conditions were potentiating factors on the spread of the virus. After quality assessment, four studies had a high risk of bias and thirteen studies were scored as moderate risk of bias. The certainty of evidence was graded as low for both outcomes evaluated. Conclusion: Considering the existing scientific evidence, warm and wet climates seem to reduce the spread of COVID-19. The certainty of the evidence generated was graded as low. However, these variables alone could not explain most of the variability in disease transmission.

positive: Essential epidemiological mechanisms underpinning the transmission dynamics of seasonal influenza Seasonal influenza has considerable impact around the world, both economically and in mortality among risk groups, but there is considerable uncertainty as to the essential mechanisms and their parametrization. In this paper, we identify a number of characteristic features of influenza incidence time series in temperate regions, including ranges of annual attack rates and outbreak durations. By constraining the output of simple models to match these characteristic features, we investigate the role played by population heterogeneity, multiple strains, cross-immunity and the rate of strain evolution in the generation of incidence time series. Results indicate that an age-structured model with non-random mixing and co-circulating strains are both required to match observed time-series data. Our work gives estimates of the seasonal peak basic reproduction number, R(0), in the range 1.6–3. Estimates of R(0) are strongly correlated with the timescale for waning of immunity to current circulating seasonal influenza strain, which we estimate is between 3 and 8 years. Seasonal variation in transmissibility is largely confined to 15–30% of its mean value. While population heterogeneity and cross-immunity are required mechanisms, the degree of heterogeneity and cross-immunity is not tightly constrained. We discuss our findings in the context of other work fitting to seasonal influenza data.

positive: COVID-19 pneumonia: CT findings of 122 patients and differentiation from influenza pneumonia OBJECTIVES: To investigate the clinical and chest CT characteristics of COVID-19 pneumonia and explore the radiological differences between COVID-19 and influenza. MATERIALS AND METHODS: A total of 122 patients (61 men and 61 women, 48 ± 15 years) confirmed with COVID-19 and 48 patients (23 men and 25 women, 47 ± 19 years) confirmed with influenza were enrolled in the study. Thin-section CT was performed. The clinical data and the chest CT findings were recorded. RESULTS: The most common symptoms of COVID-19 were fever (74%) and cough (63%), and 102 patients (83%) had Wuhan contact. Pneumonia in 50 patients with COVID-19 (45%) distributed in the peripheral regions of the lung, while it showed mixed distribution in 26 patients (74%) with influenza (p = 0.022). The most common CT features of the COVID-19 group were pure ground-glass opacities (GGO, 36%), GGO with consolidation (51%), rounded opacities (35%), linear opacities (64%), bronchiolar wall thickening (49%), and interlobular septal thickening (66%). Compared with the influenza group, the COVID-19 group was more likely to have rounded opacities (35% vs. 17%, p = 0.048) and interlobular septal thickening (66% vs. 43%, p = 0.014), but less likely to have nodules (28% vs. 71%, p < 0.001), tree-in-bud sign (9% vs. 40%, p < 0.001), and pleural effusion (6% vs. 31%, p < 0.001). CONCLUSIONS: There are significant differences in the CT manifestations of patients with COVID-19 and influenza. Presence of rounded opacities and interlobular septal thickening, with the absence of nodules and tree-in-bud sign, and with the typical peripheral distribution, may help us differentiate COVID-19 from influenza. KEY POINTS: â¢ Typical CT features of COVID-19 include pure ground-glass opacities (GGO), GGO with consolidation, rounded opacities, bronchiolar wall thickening, interlobular septal thickening, and a peripheral distribution. â¢ Presence of rounded opacities and interlobular septal thickening, with the absence of nodules and tree-in-bud sign, and with the typical peripheral distribution, may help us differentiate COVID-19 from influenza.

positive: Identifying potential undocumented COVID-19 using publicly reported influenza-like-illness and laboratory-confirmed influenza disease in the United States: An approach to syndromic surveillance? In the absence of widespread testing, syndromic surveillance approaches may be useful for understanding potential undocumented COVID-19 in the United States. We used publicly available data from the Centers for Disease Control and Prevention FluView Interactive to evaluate its potential for COVID-19 syndromic surveillance. Unlike the prior three influenza seasons, we found a 76% decrease in influenza positive tests and a 27% increase in influenza like illness during the weeks since COVID-19 outbreaks began in the United States, which suggests FluView's potential utility for COVID-19 syndromic surveillance.

positive: Relative disease burdens of COVID-19 and seasonal influenza in New York City, February 1 - April 18, 2020. Comparisons between the mortality burdens of COVID-19 and seasonal influenza often fail to account for the fact that the United States Centers for Disease Control and Prevention (CDC) reports annual influenza mortality estimates which are calculated based upon a series of assumptions about the underreporting of flu deaths. COVID-19 deaths, in contrast, are being reported as raw counts. In this report, we compare COVID-19 death counts to seasonal influenza death counts in New York City during the interval from February 1 - April 18, 2020. Using this approach, COVID-19 appears to have caused 21.4 times the number of deaths as seasonal influenza during the same period. We also assessed excess mortality in order to verify this finding. New York City has had approximately 13,032 excess all-cause mortality deaths during this time period. We assume that most of these deaths are COVID-19 related. We therefore calculated the ratio of excess deaths (i.e. assumed COVID-19 deaths) to seasonal influenza deaths during the same time interval and found a similar ratio of 21.1 COVID-19 to seasonal influenza deaths. Our findings are consistent with conditions on the ground today. Comparing COVID-19 deaths with CDC estimates of yearly influenza-related deaths would suggest that, this year, seasonal influenza has killed approximately the same number of Americans as COVID-19 has. This does not comport with the realities of the pandemic we see today.

positive: Molecular Basis of a Pandemic of Avian-Type Influenza Virus Despite heroic efforts to prevent the emergence of an influenza pandemic, avian influenza A virus has prevailed by crossing the species barriers to infect humans worldwide, occasionally with morbidity and mortality at unprecedented levels, and the virus later usually continues circulation in humans as a seasonal influenza virus, resulting in health-social-economic problems each year. Here, we review current knowledge of influenza viruses, their life cycle, interspecies transmission, and past pandemics and discuss the molecular basis of pandemic acquisition, notably of hemagglutinin (lectin) acting as a key contributor to change in host specificity in viral infection.

positive: Influenza and other emerging respiratory viruses Acute respiratory infections are one of the top five causes of mortality worldwide and contribute to >4 million deaths per year. Consequently, emerging respiratory viruses are a continuing threat to global health security and have the potential to affect our economies. Since the millennium, there have been around a dozen different outbreaks, several capturing international interest. The outbreak of severe acute respiratory syndrome coronavirus saw the beginning of an extensive global collaboration and has influenced many outbreak preparedness protocols now in place. Avian influenza is a particular threat, with cases of A(H5N1) and A(H7N9) reported most recently. Middle East respiratory syndrome coronavirus is causing continuing concerns with outbreaks in the Arabian Peninsula. Healthcare facilities worldwide play a crucial role in identifying threats and must be vigilant. Particularly important is identifying and managing emerging respiratory viruses when they are infrequently encountered. Surveillance, continuing research, vaccine and treatment developments are key to guiding the efforts and actions of healthcare workers, international health organizations, governments and other stakeholders. Each individual has a part to play in protecting our global health.

positive: Prevention and Control Strategies for SARS-CoV-2 Infection The population of 168 countries all over the world is struggling with the outbreak of COVID-19. The outbreak is declared as pandemic and public health emergency of international concern declared by WHO. SARS-CoV-2 responsible for the present health emergency exhibited close resemblance with SARS-CoV. Both the viruses are zoonotic and belong to a large family of viruses Coronaviridae. The complete virus particle is made up of four major structural proteins, namely spikes (S), nucleocapsid (N), membrane (M), and envelope (E) encoded by virus genome. The S protein of virus shows similarity to S protein of SARS-CoV. COVID-19 spreads from person to person, and this makes it more vulnerable for causing infection. Several efforts are taken to find prevention strategies for COVID-19. Researchers across the globe are working to find effective vaccination for SARS-CoV-2. There is no vaccine or medication available till date for COVID-19. Preventive measures such as social distancing, awareness, maintenance of hygiene, isolation, and movement restrictions can help in control of COVID-19 spread. Proper sanitization and cleaned and sanitized public transport can be effective in inhibiting the spread of the virus. In the present situation of medical emergency, cooperation and support by following advices from the WHO and government only facilitate everyone to come over.

positive: Coinfection of Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2)

positive: Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons Abstract Introduction Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. Objectives Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). Methods A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. Results 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. Conclusions Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.

positive: An international characterisation of patients hospitalised with COVID-19 and a comparison with those previously hospitalised with influenza Background To better understand the profile of individuals with severe coronavirus disease 2019 (COVID-19), we characterised individuals hospitalised with COVID-19 and compared them to individuals previously hospitalised with influenza. Methods We report the characteristics (demographics, prior conditions and medication use) of patients hospitalised with COVID-19 between December 2019 and April 2020 in the US (Columbia University Irving Medical Center [CUIMC], STAnford Medicine Research data Repository [STARR-OMOP], and the Department of Veterans Affairs [VA OMOP]) and Health Insurance Review & Assessment [HIRA] of South Korea. Patients hospitalised with COVID-19 were compared with patients previously hospitalised with influenza in 2014-19. Results 6,806 (US: 1,634, South Korea: 5,172) individuals hospitalised with COVID-19 were included. Patients in the US were majority male (VA OMOP: 94%, STARR-OMOP: 57%, CUIMC: 52%), but were majority female in HIRA (56%). Age profiles varied across data sources. Prevalence of asthma ranged from 7% to 14%, diabetes from 18% to 43%, and hypertensive disorder from 22% to 70% across data sources, while between 9% and 39% were taking drugs acting on the renin-angiotensin system in the 30 days prior to their hospitalisation. Compared to 52,422 individuals hospitalised with influenza, patients admitted with COVID-19 were more likely male, younger, and, in the US, had fewer comorbidities and lower medication use. Conclusions Rates of comorbidities and medication use are high among individuals hospitalised with COVID-19. However, COVID-19 patients are more likely to be male and appear to be younger and, in the US, generally healthier than those typically admitted with influenza.

positive: Using EpiRank for Analyzing Emerging Coronavirus Epidemic Patterns Huang et al. (2019) used their EpiRank algorithm, which emphasizes forward-and-backward commuter flow between homes and workplaces, to analyze the distribution patterns of two infectious diseases in Taiwan: the 2009-H1N1 influenza virus and the widespread emergence of the 2000-2008 type 71 enterovirus (EV). As this article was being prepared, the spreading mechanism of the novel coronavirus disease now designated as COVID-19 had yet to be identified, but according to the American Centers for Disease Control, its spreading mechanism and patterns are likely more similar to influenza than to other coronaviruses such as Severe Acute Respiratory Syndrome (SARS-CoV-1) or Middle East Respiratory Syndrome (MERS-CoV). To consider potential COVID-19 spatial patterns, we applied EpiRank to the 2003 SARS outbreak in north Taiwan for comparison with H1N1 and EV. SARS was found to be less contagious than H1N1 or EV, but with a significantly higher fatality rate. The characteristics of these diseases determined their specific spatial spreading patterns, as reflected in the different effects of forward and backward commuting movement. Our motivation is to highlight these differences and to illustrate EpiRank spatial patterns for the 2003 SARS outbreak for comparison with EpiRank-determined distributions for the H1N1 and EV outbreaks. Our results indicate that the daytime parameter (i.e., forward movement effect) range was slightly higher (0.5-0.55) for the SARS outbreak than for either the influenza (0.4-0.5) or EV (0.3-0.5) outbreaks, suggesting that the forward-and-backward movements of individuals between residential and core urban areas with concentrated populations were equally important regarding the spread of SARS. While COVID-19 might resemble either SARS or H1N1 in terms of spatial spreading, its daytime parameter is likely somewhere in-between, with backward movement being dominant (similar to H1N1) or with forward and backward movement being equally important (similar to SARS). Building on Huang et al. (2019) paper, we present an estimated risk distribution pattern for the Taipei Metropolitan Area for a daytime parameter of 0.55.

positive: INFECTIONS IN PREGNANCY WITH COVID-19 AND OTHER RESPIRATORY RNA VIRUS DISEASES ARE RARELY, IF EVER, TRANSMITTED TO THE FETUS: EXPERIENCES WITH CORONAVIRUSES, HPIV, hMPV RSV, AND INFLUENZA. SARS-CoV-2, the agent of COVID-19, is similar to two other coronaviruses, SARS-CoV and MERS-CoV, in causing life-threatening maternal respiratory infections and systemic complications. Because of global concern for potential intrauterine transmission of SARS-CoV-2 from pregnant women to their infants, this report analyzes the effects on pregnancy of infections caused by SARS-CoV-2 and other respiratory RNA viruses, and examines the frequency of maternal-fetal transmission with SARS-CoV-2, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, respiratory syncytial virus (RSV), parainfluenza (HPIV) and metapneumovirus (hMPV). There have been no confirmed cases of intrauterine transmission reported with COVID-19 or any other coronavirus infections. Influenza virus, despite causing approximately one billion annual infections globally, has only a few cases of confirmed or suspected intrauterine fetal infections reported. RSV is in an unusual cause of illness among pregnant women, and with the exception of one premature infant with congenital pneumonia, no other cases of maternal-fetal infection are described. Parainfluenza virus and human metapneumovirus can produce symptomatic maternal infections but do not cause intrauterine fetal infection. In summary, it appears that the absence thus far of maternal-fetal transmission of the SARS-CoV-2 virus during the COVID-19 pandemic is similar to other coronaviruses, and is also consistent with the extreme rarity of suggested or confirmed cases of intrauterine transmission of other respiratory RNA viruses. This observation has important consequences for pregnant women as it appears that if intrauterine transmission of SARSCoV-2 does eventually occur, it will be a rare event. Potential mechanisms of fetal protection from maternal viral infections are also discussed.

positive: Epidemiological parameter review and comparative dynamics of influenza, respiratory syncytial virus, rhinovirus, human coronavirus, and adenovirus Influenza-like illness (ILI) accounts for a large burden of annual morbidity and mortality worldwide. A finer-grained knowledge of the parameters and dynamics of the viruses commonly underlying ILI is needed for modeling, diagnostic, and intervention efforts. We conducted an extensive literature review for epidemiological parameter values for influenza, respiratory syncytial virus (RSV), rhinovirus, human coronavirus (HCoV), and adenovirus. We also developed a deterministic SEIR model for ILI, and derived an expression for R0. We here report ranges and means for parameters for these five common viruses.

positive: No Association of COVID-19 transmission with temperature or UV radiation in Chinese cities No Association of COVID-19 transmission with temperature or UV radiation in Chinese cities

positive: Coronavirus Pandemic as Black Swan Event Nowadays coronavirus is the hottest break news around the world. This paper aims to study why coronavirus became so meaningful for worldwide life. On one side many countries closed their boarders to prevent coronavirus spreading. On another side some people said that coronavirus is no scared than simple influence. Where is true? The health effects and mortality of coronavirus and influenza were compared. Situation Reports of World Health Organization have been analyzed and signs of Black Swan event considered. Total confirmed cases, total, deaths, and Rate of coronavirus distribution was calculated based on Situation Reports of the World Health Organization. To conclude this paper Coronavirus Pandemic recognized as Black Swan event according to considered figures and facts from recent references.

positive: [Practice and thinking of acute respiratory infection surveillance for the response of emerging respiratory diseases in Shanghai]. Shanghai Municipal Center for Disease Control and Prevention has implemented an active comprehensive surveillance project of acute respiratory infections in adults in Shanghai, including influenza like illness (ILI) and severe acute respiratory infection (SARI). By testing and identifying a variety of respiratory pathogens, it was found that influenza viruses were the main pathogens in 172 ILI cases in 2019. The positive rates of influenza A (H1N1) pdm09 virus, influenza A (H3N2) virus and influenza B virus Victoria lineage were 30.81%, 14.53% and 30.55%, respectively. The positive detection of influenza A (H1N1) pdm09 virus peaked in the first quarter. The positive rate of enterovirus/human rhinovirus was 6.40%, with a positive detection peak in the third quarter, while the positive rate of adenovirus was 4.65% with a positive detection peak in the second quarter of the year. Two human coronavirus (HCoV)-OC43 positive samples, 1 HCoV-HKU1 positive sample and 1 HCoV-NL63 positive sample were detected, respectively, and no HCoV-229E positive sample was detected. The detection rate of Staphylococcus aureus was 17.44%, and the detection rate of Klebsiella pneumoniae was 9.88%. Influenza viruses were also the main pathogens in 1 447 SARI cases. The positive rates of influenza A (H1N1) pdm09 virus, influenza A (H3N2) virus and influenza B virus Victoria lineage were 5.46%, 1.73% and 0.30%, respectively. The positive detection of influenza A (H1N1) pdm09 virus (17.50%) peaked in the first quarter. The total positive detection rate of enterovirus/human rhinovirus was 2.97%, the positive detection peaked in the first quarter. The positive rate of Mycoplasma pneumoniae was 3.25% and the positive rate of Legionella was 1.04%. 5 HCoV-229E positive samples, 10 HCoV-OC43 positive samples, 7 HCoV-HKU1 positive samples and 6 HCoV-NL63 positive samples were detected. Eight strains of Staphylococcus aureus, 4 strains of Pseudomonas aeruginosa and 3 strains of Klebsiella pneumoniae were detected after cultures. By implementing the active surveillance, we not only detected a case of human infection with avian influenza A(H7N9) virus in time, but also preliminary understood the pathogenic spectrum characteristics and seasonality of ILI and SARI in Shanghai. In recent years, the surveillance methods have been continuously improved and the number of sentinel hospitals has increased gradually. In particular, for the response to COVID-19, the Surveillance Information Reporting System of Acute Respiratory Infection based on HIS system has been promoted to cover the whole city, which might lay a foundation for the active surveillance and early warning of emerging infectious diseases in the future.

positive: Laboratory data analysis of novel coronavirus (COVID-19) screening in 2510 patients BACKGROUND: Novel coronavirus (COVID-19) is highly infectious and requires early detection, isolation, and treatment. We tried to find some useful information by analyzing the covid-19 screening data, so as to provide help for clinical practice. METHOD: We collected nucleic acid and hematology data from 2510 patients for COVID-19 infection for retrospective analysis. RESULT: COVID-19 and influenza A and B infection rates were 1.3%, 3%, and 3%, respectively. COVID-19 nucleic acid was detected in stool but not in tear samples from 8 positive patients. Among the 32 patients with COVID-19, 15 (47%) and 16 (50%) patients showed decreased lymphocyte count and lymphocyte ratio, 21(66%) and 24(75%) patients showed decreased eosinophil count and eosinophil ratio, and 18 (56%) patients showed increased C-reactive protein. Ten hematological indicators significantly differed in the blood of patients with COVID-19 and those with influenza A and B (P < 0.05). Eighteen hematological indicators significantly differed between patients with COVID-19 and negative patients (P < 0.05). CONCLUSION: The positive rate of influenza A and B infection was higher than that of COVID-19. When pharyngeal swab collection may cause infection, fecal samples can be examined. Evaluation of pharyngeal swab and fecal samples can improve the positive rate of nucleic acid detection. The COVID-19 can cause some hematological indices changes.

positive: Epidemiological characteristics and transmission model of Corona Virus Disease 2019 in China

positive: A Comparison of Clinical and Chest CT Findings in Patients With Influenza A (H1N1) Virus Infection and Coronavirus Disease (COVID-19) OBJECTIVE. The purpose of this study was to compare clinical and chest CT findings in patients with influenza A (H1N1) pneumonia and coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Thirty patients with diagnosed influenza A (H1N1) virus infection (group A) and 30 patients with diagnosed COVID-19 (group B) were retrospectively enrolled in the present study. The clinical characteristics and chest CT findings of the two groups were compared. RESULTS. Fever, cough, expectoration, and dyspnea were the main symptoms in both groups with viral pneumonia, with cough and expectoration more frequently found in group A. Lymphopenia, an elevated C-reactive protein level, and an increased erythrocyte sedimentation rate were common laboratory test findings in the two groups. The median time from symptom onset to CT in group A and group B was 6 and 15 days, respectively, and the median total CT score of the pulmonary lobes involved was 6 and 13, respectively. Linear opacification, crazy-paving sign, vascular enlargement, were more common in group B. In contrast, bronchiectasis and pleural effusion were more common in group A. Other common CT features, including peripheral or peribronchovascular distribution, ground-glass opacities (GGOs), consolidation, subpleural line, air bronchogram, and bronchial distortion, did not show statistical significance. CONCLUSION. On CT, the significant differences between influenza A (H1N1) pneumonia and COVID-19 pneumonia were findings of linear opacification, crazy-paving sign, vascular enlargement, pleural thickening, and pleural effusion, which were more common in patients with COVID-19 pneumonia, and bronchiectasis and pleural effusion, which were more common in patients with influenza A (H1N1) pneumonia. Other imaging findings, including peripheral or peribronchovascular distribution, ground-glass opacities (GGO), consolidation, subpleural line, air bronchogram, and bronchial distortion, were not significantly different between the two patient groups.

positive: Home collection of nasal swabs for detection of influenza in the Household Influenza Vaccine Evaluation Study Background: Community based studies of influenza and other respiratory viruses (e.g. SARS-COV-2) require laboratory confirmation of infection. During the current COVID-19 pandemic, social distancing guidelines require alternative data collection in order protect both research staff and participants. Home-collected respiratory specimens are less resource intensive, can be collected earlier after symptom onset, and provide a low-contact means of data collection. A prospective, multi-year, community-based cohort study is an ideal setting to examine the utility of home-collected specimens for identification of influenza. Methods: We describe the feasibility and reliability of home-collected specimens for the detection of influenza. We collected data and specimens between October 2014 and June 2017 from the Household Influenza Vaccine Evaluation (HIVE) Study. Cohort participants were asked to collect a nasal swab at home upon onset of acute respiratory illness. Research staff also collected nose and throat swab specimens in the study clinic within 7 days of onset. We estimated agreement using Cohen's kappa and calculated sensitivity and specificity of home-collected compared to staff-collected specimens. Results: We tested 336 paired staff- and home-collected respiratory specimens for influenza by RT-PCR; 150 staff-collected specimens were positive for influenza A/H3N2, 23 for influenza A/H1N1, 14 for influenza B/Victoria, and 31 for influenza B/Yamagata. We found moderate agreement between collection methods for influenza A/H3N2 (0.70) and B/Yamagata (0.69) and high agreement for influenza A/H1N1 (0.87) and B/Victoria (0.86). Sensitivity ranged from 78-86% for all influenza types and subtypes. Specificity was high for influenza A/H1N1 and both influenza B lineages with a range from 96-100%, and slightly lower for A/H3N2 infections (88%). Conclusions: Collection of nasal swab specimens at home is both feasible and reliable for identification of influenza virus infections.

positive: Robust Estimation of Infection Fatality Rates during the Early Phase of a Pandemic During a pandemic, robust estimation of case fatality rates (CFRs) is essential to plan and control suppression and mitigation strategies. At present, estimates for the CFR of COVID-19 caused by SARS-CoV-2 infection vary considerably. Expert consensus of 0.1-1% covers in practical terms a range from normal seasonable Influenza to Spanish Influenza. In the following, I deduce a formula for an adjusted Infection Fatality Rate (IFR) to assess mortality in a period following a positive test adjusted for selection bias. Official datasets on cases and deaths were combined with data sets on number of tests. After data curation and quality control, a total of IFR (n=819) was calculated for 21 countries for periods of up to 26 days between registration of a case and death. Estimates for IRFs increased with length of period, but levelled off at >9days with a median for all 21 countries of 0.11 (95%-CI: 0.073-0.15). An epidemiologically derived IFR of 0.040 % (95%-CI: 0.029%-0.055%) was determined for Iceland and was very close to the calculated IFR of 0.057% (95%-CI: 0.042-0.078), but 2.7-6-fold lower than CFRs. IFRs, but not CFRs, were positively associated with increased proportions of elderly in age-cohorts (n=21, spearman's ρ =.73, p =.02). Real-time data on molecular and serological testing may further displace classical diagnosis of disease and its related death. I will critically discuss, why, how and under which conditions the IFR, provides a more solid early estimate of the global burden of a pandemic than the CFR.

positive: Excess cases of influenza suggest an earlier start to the coronavirus epidemic in Spain than official figures tell us: an analysis of primary care electronic medical records from over 6 million people from Catalonia Objectives: There is uncertainty about when the first cases of COVID-19 appeared in Spain, as asymptomatic patients can transmit the virus. We aimed to determine whether influenza diagnoses masked early COVID-19 cases and, if so, estimate numbers of undetected COVID-19 cases in a large database of primary-care records covering >6 million people in Catalonia. Design: Time-series study of influenza and COVID-19 cases, using all influenza seasons from autumn-winter 2010-2011 to autumn-winter 2019-2020. Setting: Primary care, Catalonia, Spain. Participants: People registered in one of the contributing primary-care practices, covering >6 million people and >85% of the population. Main outcome measures: Weekly new cases of influenza and COVID-19 diagnosed in primary care. Analyses: Daily counts of both cases were computed using the total cases recorded over the previous 7 days to avoid weekly effects on recording practice. Epidemic curves were characterised for the 2010-2011 to 2019-2020 influenza seasons. Influenza seasons with a similar epidemic curve and peak case number as the 2019-2020 season were used to model predictions for 2019-2020. ARIMA models were fitted to the included influenza seasons, overall and stratified by age, to estimate expected case numbers. Daily excess influenza cases were defined as the number of observed minus expected cases. Results: Four influenza season curves (2011-2012, 2012-2013, 2013-2014, and 2016-2017) were used to estimate the number of expected cases of influenza in 2019-2020. Between 4 February 2020 and 20 March 20202, 8,017 (95% CI: 1,841 to 14,718) excess influenza cases were identified. This excess was highest in the 15-64 age group. Conclusions: COVID-19 cases may have been present in the Catalan population when the first imported case was reported on 25 February 2020. COVID-19 carriers may have been misclassified as influenza diagnoses in primary care, boosting community transmission before public health measures were taken. In future, the surveillance of excess influenza cases using widely available primary-care electronic medical records could help detect new outbreaks of COVID-19 or other influenza-like illness-causing pathogens. Earlier detection would allow public health responses to be initiated earlier than during the current crisis.

positive: COVID-19 versus seasonal influenza 2019–2020: USA Severe mitigation efforts in the USA to reduce the incidence of COVID-19 infections have led to a massive rise in unemployment, social disruption, and appear to be leading to a severe economic depression. In contrast, no such interventions were regarded as necessary to manage seasonal influenza in 2019–2020. Another mitigation approach is proposed for COVID-19 that would allow society to function and yet should still be effective.

positive: Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1 Human coronaviruses (HCoVs) cause mild to severe respiratory diseases. Six types of HCoVs have been discovered, the most recent one termed the Middle East respiratory syndrome coronavirus (MERS-CoV). The aim of this study is to monitor the circulation of HCoV types in the population during 2015–2016 in Israel. HCoVs were detected by real-time PCR analysis in 1910 respiratory samples, collected from influenza-like illness (ILI) patients during the winter sentinel influenza survey across Israel. Moreover, 195 HCoV-positive samples from hospitalized patients were detected during one year at Soroka University Medical Center. While no MERS-CoV infections were detected, 10.36% of patients in the survey were infected with HCoV-OC43 (43.43%), HCoV-NL63 (44.95%), and HCoV-229E (11.62%) viruses. The HCoVs were shown to co-circulate with respiratory syncytial virus (RSV) and to appear prior to influenza virus infections. HCoV clinical symptoms were more severe than those of RSV infections but milder than influenza symptoms. Hospitalized patients had similar HCoV types percentages. However, while it was absent from the public winter survey, 22.6% of the patients were HCoV-HKU1 positives, mainly during the spring-summer period.

positive: Impact assessment of non-pharmaceutical interventions against COVID-19 and influenza in Hong Kong: an observational study Background: A range of public health measures have been implemented to delay and reduce local transmission of COVID-19 in Hong Kong, and there have been major changes in behaviours of the general public. We examined the effect of these interventions and behavioral changes on the incidence of COVID-19 as well as on influenza virus infections which may share some aspects of transmission dynamics with COVID-19. Methods: We reviewed policy interventions and measured changes in population behaviours through two telephone surveys, on January 20-23 and February 11-14. We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (R_t), for COVID-19 and influenza A(H1N1). Findings: COVID-19 transmissibility has remained at or below 1, indicating successful containment to date. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% confidence interval, CI: 34% to 53%) reduction in transmissibility in the community, and a 33% (95% CI: 24% to 43%) reduction in transmissibility based on paediatric hospitalization rates. In the two surveys we estimated that 74.5% and 97.5% of the general adult population wore masks when going out, and 61.3% and 90.2% avoided going to crowded places, respectively. Implications: Containment measures, social distancing measures and changes in population behaviour have successfully prevented spread of COVID-19. The social distancing measures and behavioural changes led to a substantial reduction in influenza transmission in early February 2020. However, it may be challenging to avoid fatigue and sustain these measures and population behaviours as COVID-19 continues to spread globally. Funding: Health and Medical Research Fund, Hong Kong

positive: Prediction and analysis of Coronavirus Disease 2019 In December 2019, a novel coronavirus was found in a seafood wholesale market in Wuhan, China. WHO officially named this coronavirus as COVID-19. Since the first patient was hospitalized on December 12, 2019, China has reported a total of 78,824 confirmed CONID-19 cases and 2,788 deaths as of February 28, 2020. Wuhan's cumulative confirmed cases and deaths accounted for 61.1% and 76.5% of the whole China mainland , making it the priority center for epidemic prevention and control. Meanwhile, 51 countries and regions outside China have reported 4,879 confirmed cases and 79 deaths as of February 28, 2020. COVID-19 epidemic does great harm to people's daily life and country's economic development. This paper adopts three kinds of mathematical models, i.e., Logistic model, Bertalanffy model and Gompertz model. The epidemic trends of SARS were first fitted and analyzed in order to prove the validity of the existing mathematical models. The results were then used to fit and analyze the situation of COVID-19. The prediction results of three different mathematical models are different for different parameters and in different regions. In general, the fitting effect of Logistic model may be the best among the three models studied in this paper, while the fitting effect of Gompertz model may be better than Bertalanffy model. According to the current trend, based on the three models, the total number of people expected to be infected is 49852-57447 in Wuhan,12972-13405 in non-Hubei areas and 80261-85140 in China respectively. The total death toll is 2502-5108 in Wuhan, 107-125 in Non-Hubei areas and 3150-6286 in China respetively. COVID-19 will be over p robably in late-April, 2020 in Wuhan and before late-March, 2020 in other areas respectively.

positive: Differential diagnosis of pandemic (H1N1) 2009 infection by detection of haemagglutinin with an enzyme-linked immunoassay A sensitive and convenient immunoassay that can directly differentiate pandemic (H1N1) 2009 (pH1N1) virus from seasonal influenza virus can play an important role in the clinic. In the presented study, a double-sandwich ELISA (pH1N1 ELISA), based on two monoclonal antibodies against haemagglutinin (HA) of the pH1N1 virus, was developed. After laboratory determination of the sensitivity and specificity characteristics, the performance of this assay was evaluated in a cohort of 904 patients with influenza-like illness. All seven strains of pH1N1 virus tested were positive by pH1N1 ELISA, with an average lower detection limit of 10(3.0 ± 0.4) tissue culture infective dose (TCID)(50)/mL (or 0.009 ± 0.005 HA titre). Cross-reaction of the assay with seasonal influenza virus and other common respiratory pathogens was rare. In pH1N1-infected patients, the sensitivity of the pH1N1 ELISA was 92.3% (84/91, 95% CI 84.8–96.9%), which is significantly higher than that of the BD Directigen EZ Flu A + B test (70.3%, p <0.01). The specificity of pH1N1 ELISA in seasonal influenza A patients was 100.0% (171/171, 95% CI 97.9–100.0%), similar to that in non-influenza A patients (640/642, 99.7%, 95% CI 98.9–100.0%). The positive predictive value for pH1N1 ELISA was 97.7% and the negative predictive value was 99.1% in this study population with a pH1N1 prevalence of 10.1%. In conclusion, detection of HA of pH1N1 virus by immunoassay appears to be a convenient and reliable method for the differential diagnosis of pH1N1 from other respiratory pathogens, including seasonal influenza virus.

positive: Is SARS-CoV-2 Also an Enteric Pathogen With Potential Fecal-Oral Transmission? A COVID-19 Virological and Clinical Review In as few as 3 months, coronavirus disease 2019 (COVID-19) has spread and ravaged the world at an unprecedented speed in modern history, rivaling the 1918 flu pandemic. Severe acute respiratory syndrome coronavirus-2, the culprit virus, is highly contagious and stable in the environment and transmits predominantly among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that severe acute respiratory syndrome coronavirus-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.

positive: Coronavirus Disease 2019 and Influenza 2019-2020

positive: The December 2019 New Corona Virus (SARS-CoV-2) Outbreak: A Behavioral Infectious Disease Policy Model It is critical to understand the impact of distinct policy interventions to the ongoing December 2019 coronavirus (SARS-CoV-2) pandemic. We develop a flexible behavioral, dynamic, and sectorial epidemic policy model comprising both endogenous virus transmission and public health and citizen responses. Applicable to the full epidemic cycle including resurgence, the model allows exploring the multivariate impact of distinct policy interventions, including general and targeted testing and social contact reduction efforts. Calibrating the model to the early SARS-CoV-2 outbreak at the level of continents, we demonstrate how early, rapid, and extensive buildup of testing and social contact reduction efforts interplay to suppress the outbreak. Next, applying the model within hypothetical contexts we demonstrate how: i) sociodemographic variation in vulnerability to the virus affects overall reported and actual outbreak patterns; ii) feasible timing of deconfinement depends on earlier responses to the outbreak; and, iii) targeted approaches help suppress resurgent outbreaks and their various impacts. Finally, given the importance of broad support of outbreak control efforts, across public health experts, policymakers, volunteers, media, and citizens, we make the model also accessible in the form of a free web-based management flight simulator.

positive: Global Trends in Epidemiology of Coronavirus Disease 2019 (COVID-19) In December 2019, suddenly 54 cases of viral pneumonia emerged in Wuhan, China, caused by some unknown microorganism. The virus responsible for these pneumonia infections was identified as novel coronavirus of the family Coronaviridae. The novel coronavirus was renamed as COVID-19 by WHO. Infection from the virus has since increased exponentially and has spread all over the world in more than 196 countries. The WHO has declared a Public Health Emergency of International Concern due to the outbreak of COVID-19. The virus is highly infectious and can cause human-to-human transmission. Every 24 h, cases of COVID-19 increase severalfolds. The WHO is monitoring the SARS-CoV-2 spread very closely via a global surveillance system. The current situation demands the enforcement of strict laws which would help in inhibiting the further spread of COVID-19. Social distancing, international travel restrictions to affected countries, and hygiene are three important ways to nullify SARS-CoV-2.Government and private organizations need to come forward and work together during this pandemic. Public awareness, social distancing, and sterilization must be maintained to neutralize the viral infection, especially in major hot spots.

positive: The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike Protein Enhance Spike Protein-ACE2 Binding The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. Many studies have been conducted to target the structures of RBD-ACE2 binding and to design RBD-targeting vaccines and drugs. Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility and antibody can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein-ACE2 binding. Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD-ACE2 binding affinity. A negatively charged tetrapeptide (GluGluLeuGlu) is then designed to neutralize the positively charged arginine on the polybasic cleavage sites. We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD-ACE2 binding strength. This significant binding energy reduction demonstrates the feasibility to neutralize RBD-ACE2 binding by targeting this specific polybasic cleavage site. Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection. TOC: The SARS-CoV-2 spike protein-ACE2 complex showing the polybasic cleavage sites

positive: Targeted Immunosuppression Distinguishes COVID-19 from Influenza in Moderate and Severe Disease Coronavirus disease 2019 (COVID-19) is characterized by a high incidence of acute respiratory failure. The underlying immunopathology of that failure and how it compares to other causes of severe respiratory distress, such as influenza virus infection, are not fully understood. Here we addressed this by developing a prospective observational cohort of COVID-19 and influenza subjects with varying degrees of disease severity and assessing the quality and magnitude of their immune responses at the cellular and protein level. Additionally, we performed single-cell RNA transcriptional profiling of peripheral blood mononuclear cells from select subjects. The cohort consists of 79 COVID-19 subjects, 26 influenza subjects, and 15 control subjects, including 35 COVID-19 and 7 influenza subjects with acute respiratory failure. While COVID-19 subjects exhibited largely equivalent or greater activated lymphocyte counts compared to influenza subjects, they had fewer monocytes and lower surface HLA-class II expression on monocytes compared to influenza subjects and controls. At least two distinct immune profiles were observed by cytokine levels in severe COVID-19 patients: 3 of 71 patients were characterized by extreme inflammation, with greater than or equal to ~50% of the 35 cytokines measured greater than 2 standard deviations from the mean level of other severe patients (both influenza and COVID-19); the other immune profile, which characterized 68 of 71 subjects, had a mixed inflammatory signature, where 28 of 35 cytokines in COVID-19 patients had lower mean cytokine levels, though not all were statistically significant. Only 2 cytokines were higher in COVID-19 subjects compared to influenza subjects (IL-6 and IL-8). Influenza and COVID-19 patients could be distinguished statistically based on cytokine module expression, particularly after controlling for the significant effects of age on cytokine expression, but again with lower levels of most cytokines in COVID-19 subjects. Further, high circulating levels of IL-1RA and IL-6 were associated with increased odds of intubation in the combined influenza and COVID-19 cohort [OR = 3.93 and 4.30, respectively] as well as among only COVID-19 patients. Single cell transcriptional profiling of COVID-19 and influenza subjects with respiratory failure identified profound suppression in type I and type II interferon signaling in COVID-19 patients across multiple clusters. In contrast, COVID-19 cell clusters were enriched for alterations in metabolic, stress, and apoptotic pathways. These alterations were consistent with an increased glucocorticoid response in COVID-19 patients compared to influenza. When considered across the spectrum of innate and adaptive immune profiles, the immune pathologies underlying severe influenza and COVID-19 are substantially distinct. The majority of COVID-19 patients with acute respiratory failure do not have a cytokine storm phenotype but instead exhibit profound type I and type II IFN immunosuppression when compared to patients with acute influenza. Upregulation of a small number of inflammatory mediators, including IL-6, predicts acute respiratory failure in both COVID-19 and influenza patients.

positive: COVID-19 outbreak in Greece has passed its rising inflection point and stepping into its peak Since the beginning of 2020, COVID-19 is the most urgent and challenging task for the international scientific community, in order to identify its behaviour, track its progress and plan effective mitigation policies. In this study, Greece is the main focus for assessing the national outbreak and estimating the general trends and outlook of it. Multiple data analytics procedures, spectral decomposition and curve-fitting formulations are developed based on the data available at hand. Standard SIEQRDP epidemic modelling is applied for Greece and for the general region around it, providing hints for the outbreak progression in the mid- and long-term, for various infections under-reporting rates. The overall short-term outlook for Greece seems to be towards positive, with a downward trend in infections rate daily increase (i.e., now beyond the exponential growth rate), a possible peak within a few days beyond April 14th, as well as the high availability level of ICU w.r.t. expected demand at peak. On the negative side, the fade-out period seems to be in the order of several months, with high probability of recurrent surges of the outbreak. The mitigation policies for the `next day' should be focused on close tracking of the epidemic via large-scale tests, strict border checking in international travelling and an adaptive plan for selective activation of mitigation measures when deemed necessary.

positive: Co-infection in SARS-CoV-2 infected Patients: Where Are Influenza Virus and Rhinovirus/Enterovirus? Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a global pandemic. Our goal was to determine whether coinfections with other respiratory pathogens occur in a significant subset of SARS-CoV-2 infected patients in the greater New York City metropolitan area. During the period from March 16, 2020 through April 20, 2020, our laboratory detected SARS-CoV-2 infection in 8,990 patients of a total 18,704 tested by real-time reverse-transcription-polymerase-chain-reaction amplification (SARS-CoV-2 Test, cobas® 6800 system, RocheDiagnostics). Amongst the patients who tested positive for SARS-CoV-2, 1,204 were also tested for other respiratory viruses, and concurrent infection was found in only 36 (< 3%). In comparison, coinfection with at least one non-SARS-CoV-2 respiratory viral pathogen was found in 13.1% of patients who tested negative for SARS-CoV-2. Additionally, in patients who tested negative for SARS-CoV-2, the most common respiratory virus co-infections were those commonly seen circulating in the community including rhinovirus/enterovirus, influenza viruses and coronavirus NL63, whereas non-SARS-CoV-2 coronaviridae were the most common concurrent respiratory viruses found in SARS-CoV-2 -positive patients. Additional studies are needed to establish whether simultaneous viral infection in SARS-CoV-2 patients could potential drive viral interference or influence disease outcomes. This article is protected by copyright. All rights reserved.

positive: How diseases rise and fall with the seasons—and what it could mean for coronavirus Scientists and doctors have observed for thousands of years that some diseases, such as polio and influenza, rise and fall with the seasons But why? Ongoing research in animals and humans suggests a variety of causes, including changes in the environment (like pH, temperature, and humidity) and even seasonal and daily changes to our own immune systems Figuring out those answers could one day make all the difference in minimizing the impact of infectious disease outbreaks—such as coronavirus disease 2019

positive: Forecasting national and regional influenza-like illness for the USA Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.

positive: Seasonality and selective trends in viral acute respiratory tract infections Abstract Influenza A and B, and many unrelated viruses including rhinovirus, RSV, adenovirus, metapneumovirus and coronavirus share the same seasonality, since these viral acute respiratory tract infections (vARIs) are much more common in winter than summer. Unfortunately, early investigations that used recycled “pedigree” virus strains seem to have led microbiologists to dismiss the common folk belief that vARIs often follow chilling. Today, incontrovertible evidence shows that ambient temperature dips and host chilling increase the incidence and severity of vARIs. This review considers four possible mechanisms, M1 - 4, that can explain this link: (M1) increased crowding in winter may enhance viral transmission; (M2) lower temperatures may increase the stability of virions outside the body; (M3) chilling may increase host susceptibility; (M4) lower temperatures or host chilling may activate dormant virions. There is little evidence for M1 or M2, which are incompatible with tropical observations. Epidemiological anomalies such as the repeated simultaneous arrival of vARIs over wide geographical areas, the rapid cessation of influenza epidemics, and the low attack rate of influenza within families are compatible with M4, but not M3 (in its simple form). M4 seems to be the main driver of seasonality, but M3 may also play an important role.

positive: [Be alert to superposed effect of seasonal influenza while fighting against COVID-19] COVID-19 continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the COVID-19 epidemic.

positive: Modelling the Extremes of Seasonal Viruses and Hospital Congestion: The Example of Flu in a Swiss Hospital Viruses causing flu or milder coronavirus colds are often referred to as"seasonal viruses"as they tend to subside in warmer months. In other words, meteorological conditions tend to impact the activity of viruses, and this information can be exploited for the operational management of hospitals. In this study, we use three years of daily data from one of the biggest hospitals in Switzerland and focus on modelling the extremes of hospital visits from patients showing flu-like symptoms and the number of positive cases of flu. We propose employing a discrete Generalized Pareto distribution for the number of positive and negative cases, and a Generalized Pareto distribution for the odds of positive cases. Our modelling framework allows for the parameters of these distributions to be linked to covariate effects, and for outlying observations to be dealt with via a robust estimation approach. Because meteorological conditions may vary over time, we use meteorological and not calendar variations to explain hospital charge extremes, and our empirical findings highlight their significance. We propose a measure of hospital congestion and a related tool to estimate the resulting CaRe (Charge-at-Risk-estimation) under different meteorological conditions. The relevant numerical computations can be easily carried out using the freely available GJRM R package. The introduced approach could be applied to several types of seasonal disease data such as those derived from the new virus SARS-CoV-2 and its COVID-19 disease which is at the moment wreaking havoc worldwide. The empirical effectiveness of the proposed method is assessed through a simulation study.

positive: Does susceptibility to novel coronavirus (COVID-19) infection differ by age?: Insights from mathematical modelling Among Italy, Spain, and Japan, the age distributions of novel coronavirus (COVID-19) mortality show only small variation even though the number of deaths per country shows large variation. To understand the determinant for this situation, we constructed a mathematical model describing the transmission dynamics and natural history of COVID-19 and analyzed the dataset of fatal cases of COVID-19 in Italy, Spain, and Japan. We estimated the parameter which describes the age-dependency of susceptibility by fitting the model to reported data, taking into account the effect of change in contact patterns during the outbreak of COVID-19, and the fraction of symptomatic COVID-19 infections. Our modelling study revealed that if the mortality rate or the fraction of symptomatic infections among all COVID-19 cases does not depend on age, then unrealistically different age-dependencies of susceptibilities against COVID-19 infections between Italy, Japan, and Spain are required to explain the similar age distribution of mortality but different basic reproduction numbers (R0). Variation of susceptibility by age itself cannot explain the robust age distribution in mortality by COVID-19 in those three countries, however it does suggest that the age-dependencies of i) the mortality rate and ii) the fraction of symptomatic infections among all COVID-19 cases determine the age distribution of mortality by COVID-19.

positive: Comprehensive overview of COVID‐19 based on current evidence In December 2019, twenty‐seven pneumonia patients with unknown causes originated in South China seafood market in Wuhan. The virus infection spread rapidly and swept through China in less than a month. Subsequently, the virus was proven a novel coronavirus and named SARS‐CoV‐2. The outbreak of novel coronavirus has been determined as a Public Health Emergency of International Concern (PHEIC) by WHO on January 31, 2020. Similar to other coronaviruses like the Middle East Respiratory Syndrome (MERS) CoV and Severe Acute Respiratory Syndrome (SARS) CoV, the novel coronavirus was reported to spread via respiratory droplets and close contact from human to human, which means the virus is highly infectious and dangerous. Unfortunately, till now the virus has spread to over 200 countries/territories/areas around the world and the Coronavirus Disease 2019 (COVID‐19) outbreak is continuing to grow. Currently, information sharing and transparency are essential for risk assessment and epidemic control in all endemic areas. In this article, we compared SARS‐CoV‐2 with SARS‐CoV and influenza virus, discussed current researching progress of COVID‐19, including clinical characteristics, pathological changes, treatment measures, and so on.

positive: A Review of Coronavirus Disease-2019 (COVID-19) There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

positive: Susceptible supply limits the role of climate in the COVID-19 pandemic Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios of climate-dependence based on known coronavirus biology. We find that while variations in humidity may be important for endemic infections, during the pandemic stage of an emerging pathogen such as SARS-CoV-2 climate may drive only modest changes to pandemic size and duration. Our results suggest that, in the absence of effective control measures, significant cases in the coming months are likely to occur in more humid (warmer) climates, irrespective of the climate-dependence of transmission and that summer temperatures will not substantially limit pandemic growth.

positive: Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020 Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R(0) of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.

negative: Avian influenza H5N1 in viverrids: implications for wildlife health and conservation. The Asian countries chronically infected with avian influenza A H5N1 are 'global hotspots' for biodiversity conservation in terms of species diversity, endemism and levels of threat. Since 2003, avian influenza A H5N1 viruses have naturally infected and killed a range of wild bird species, four felid species and a mustelid. Here, we report fatal disseminated H5N1 infection in a globally threatened viverrid, the Owston's civet, in Vietnam, highlighting the risk that avian influenza H5N1 poses to mammalian and avian biodiversity across its expanding geographic range.

negative: A Mathematical Description of the Dynamics of Coronavirus Disease (COVID-19): A Case Study of Brazil This paper deals with the mathematical modeling and numerical simulations related to the coronavirus dynamics. A description is developed based on the framework of susceptible-exposed-infectious-recovered model. Initially, a model verification is carried out calibrating system parameters with data from China, Italy, Iran and Brazil. Afterward, numerical simulations are performed to analyzed different scenarios of COVID-19 in Brazil. Results show the importance of governmental and individual actions to control the number and the period of the critical situations related to the pandemic.

negative: Age-adjusted associations between comorbidity and outcomes of COVID-19: a review of the evidence Background: Current evidence suggests that older people and people with underlying comorbidities are at increased risk of severe disease and death following hospitalisation with COVID-19. As comorbidity increases with age, it is necessary to understand the age-adjusted relationship between comorbidity and COVID-19 outcomes, in order to enhance planning capabilities and our understanding of COVID-19. Methods: We conducted a rapid, comprehensive review of the literature up to 10 April 2020, to assess the international empirical evidence on the association between comorbidities and severe or critical care outcomes of COVID-19, after accounting for age, among hospitalised patients with COVID-19. Results: After screening 579 studies, we identified seven studies eligible for inclusion and these were synthesised narratively. All were from China. The emerging evidence base mostly indicates that after adjustment for age (and in some cases other potential confounders), obesity, hypertension, diabetes mellitus, chronic obstructive airways disease (COPD), and cancer are all associated with worse outcomes. The largest study, using a large nationwide sample of COVID-19 patients in China, found that those with multiple comorbidities had more than twice the risk of a severe outcome or death compared with patients with no comorbidities, after adjusting for age and smoking (HR=2.59, 95% CI 1.61, 4.17). Conclusions: This review summarises for clinicians, policymakers, and academics the most robust evidence to date on this topic, to inform the management of patients and control measures for tackling the pandemic. Given the intersection of comorbidity with ethnicity and social disadvantage, these findings also have important implications for health inequalities. As the pandemic develops, further research should confirm these trends in other settings outside China and explore mechanisms by which various underlying health conditions increase risk of severe COVID-19.

negative: Comparison of bovine coronavirus (BCV) antigens: Monoclonal antibodies to the spike glycoprotein distinguish between vaccine and wild-type strains Abstract Monoclonal antibodies (MAbs) against two major structural proteins of the cell-adapted Mebus strain of bovine coronavirus (BCV-L9) were produced and characterized. Seven MAbs reacted with the peplomeric glycoprotein, gp100/S, while three MAbs reacted with the nucleoprotein p53/N in Western blot analysis of BCV polypeptides. MAbs to gp100/S reacted with discontinuous epitopes of gp100/S in Westerns under mild but not under standard denaturing conditions. In contrast, MAbs to p53/N reacted in both types of Westerns, and those epitopes were thus continuous. MAbs to p53/N failed to neutralize BCV infectivity, while 4 MAbs to gp100/S neutralized BCV effectively. Cross reactivity of MAbs to gp100/S specified by five virulent wild-type strains and two high passage, cell-culture-adapted strains in mildly denaturing Westerns and neutralization assays indicated that two epitopes were conserved in all seven strains, while two epitopes of the avirulent strains were not detected in the wild-type strains. Non-neutralizing MAbs of gp100/S reacted with all seven strains in Westerns with the exception of one MAb that was specific for the highly cell-adapted strain BCV-L9.

negative: COVID-19: Review of Epidemiology and Potential Treatments Against 2019 Novel Coronavirus An epidemic of extreme respiratory deterrence, pneumonia and shortness of breath, the SARS-CoV-2 viral infection began in Wuhan, Hubei Province, China in December 2019, and rapidly spread across China and beyond, with human to human transmission. On February 12, 2020, World Health Organization officially named the new coronavirus disease as coronavirus disease 19 (COVID-19). Most COVID-19 patients were diagnosed with pneumonia and many were treated using Chinese medicines and other secondary therapies. As of April 22, 2020, the total figure of infected patients has crossed 2.6 million people worldwide with over 180,000 deaths and 700,000 patients that have recovered. Preliminary reports suggest that certain drugs, such as chloroquine and antiviral nucleotide analogues such as remdesivir, which inhibit viral replication, can target the new coronavirus, although their usefulness in the clinic is still under debate. An expert US committee developed the US NIH guidelines for COVID-19 treatment, which was just released and will be regularly updated. This manuscript reviews the epidemiology, etiology, mortality, COVID-19 clinical symptoms, and potential therapeutic drugs, while highlighting the seriousness and damage-induced by SARS-CoV-2.

negative: Human Coronavirus-Associated Influenza-Like Illness in the Community Setting in Peru. We present findings describing the epidemiology of non-severe acute respiratory syndrome human coronavirus-associated influenza-like illness from a population-based active follow-up study in four different regions of Peru. In 2010, the prevalence of infections by human coronaviruses 229E, OC43, NL63, or HKU1 was 6.4% in participants with influenza-like illness who tested negative for influenza viruses. Ten of 11 human coronavirus infections were identified in the fall-winter season. Human coronaviruses are present in different regions of Peru and are relatively frequently associated with influenza-like illness in Peru.

negative: Pilot Evaluation of RT-PCR/Electrospray Ionization Mass Spectrometry (PLEX-ID/Flu assay) on Influenza-Positive Specimens The PLEX-ID/Flu assay has been recently developed to enable the detection and typing of influenza viruses based on the RT-PCR/electrospray ionization mass spectrometry technology. This novel assay was evaluated for typing performance on 201 positive influenza A or B nasopharyngeal swab specimens (NPS) detected by real-time RT-PCR during the 2010-2011 season. The PLEX-ID/Flu assay detected and characterized 91.3% and 95.3% of all influenza A and B samples, respectively. All non-typeable influenza A and B specimens by the assay showed low viral loads with threshold cycle values ≥ 33. Taken together, and although our results need to be confirmed by further prospective studies, the PLEX-ID/Flu assay detected positively and gave a typing result for 93% of all NPS detected positively by real-time RT-PCR, thus suggesting a potential role for influenza virus surveillance among other techniques.

negative: A novel human coronavirus: Middle East respiratory syndrome human coronavirus In 2012, a novel coronavirus, initially named as human coronavirus EMC (HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus (MERS-CoV), was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death. Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus, including 34 deaths to date. This novel coronavirus is culturable and two complete genome sequences are now available. Furthermore, molecular detection and indirect immunofluorescence assay have been developed. The present paper summarises the limited recent advances of this novel human coronavirus, including its discovery, genomic characterisation and detection.

negative: Vaccinating children against influenza: overall cost-effective with potential for undesirable outcomes BACKGROUND: The present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands. This requires an evaluation of the long-term impact of such a program on the burden of influenza across all age groups, using a transmission model that accounts for the seasonal variability in vaccine effectiveness and the shorter duration of protection following vaccination as compared to natural infection. METHODS: We performed a cost-effectiveness analysis based on a stochastic dynamic transmission model that has been calibrated to reported GP visits with influenza-like illness in the Netherlands over 11 seasons (2003/2004 to 2014/2015). We analyzed the costs and effects of extending the current program with vaccination of children aged 2–16 years at 50% coverage over 20 consecutive seasons. We measured the effects in quality-adjusted life-years (QALYs) and we adopted a societal perspective. RESULTS: The childhood vaccination program is estimated to have an average incremental cost-effectiveness ratio (ICER) of €3944 per QALY gained and is cost-effective in the general population (across 1000 simulations; conventional Dutch threshold of €20,000 per QALY gained). The childhood vaccination program is not estimated to be cost-effective for the target-group itself with an average ICER of €57,054 per QALY gained. Uncertainty analyses reveal that these ICERs hide a wide range of outcomes. Even though introduction of a childhood vaccination program decreases the number of infections, it tends to lead to larger epidemics: in 23.3% of 1000 simulations, the childhood vaccination program results in an increase in seasons with a symptomatic attack rate larger than 5%, which is expected to cause serious strain on the health care system. In 6.4% of 1000 simulations, the childhood vaccination program leads to a net loss of QALYs. These findings are robust across different targeted age groups and vaccination coverages. CONCLUSIONS: Modeling indicates that childhood influenza vaccination is cost-effective in the Netherlands. However, childhood influenza vaccination is not cost-effective when only outcomes for the children themselves are considered. In approximately a quarter of the simulations, the introduction of a childhood vaccination program increases the frequency of seasons with a symptomatic attack rate larger than 5%. The possibility of an overall health loss cannot be excluded.

negative: A simple statistical physics model for the epidemic with incubation period Based on the classical SIR model, we derive a simple modification for the dynamics of epidemics with a known incubation period of infection. The model is described by a system of integro-differential equations. Parameters of our model directly related to epidemiological data. We derive some analytical results, as well as perform numerical simulations. We use the proposed model to analyze COVID-19 epidemic data in Armenia. We propose a strategy: organize a quarantine, and then conduct extensive testing of risk groups during the quarantine, evaluating the percentage of the population among risk groups and people with symptoms.

negative: Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients’ lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.

negative: How sick will the coronavirus make you? The answer may be in your genes COVID-19, caused by the new pandemic coronavirus, is strangely—and tragically—selective Only some infected people get sick, and although most of the critically ill are elderly or have complicating problems such as heart disease, some killed by the disease are previously healthy and even relatively young Researchers are now gearing up to scour the patients’ genomes for DNA variations that explain this mystery The findings could be used to identify those most at risk of serious illness and those who might be protected, and they might also guide the search for new treatments

negative: The role of the radiologist in diagnosing the COVID-19 infection. Parma experiences. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the coronavirus disease 2019 (COVID-19), a respiratory disease that ranges from an asymptomatic or mild flu-like illness to severe pneumonia, multiorgan failure, and death. Imaging might play an important role in clinical decision making by supporting rapid triage of patients with suspected COVID-19 and assessing supervening complications, such as super-added bacterial infection and thrombosis. Further studies will clarify the real impact of imaging on COVID-19 patients' management and the potential role of radiology in future outbreaks.

negative: ScRNA-seq discover cell cluster change under OAB: ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway Objective Previous study indicated that bladder cells which express ACE2 were a potential infection route of 2019-nCov. This study observed some differences of bladder cell cluster and their ACE2 expression between OAB mice and healthy mice, indicating the change of infectious possibility and pathway under overactive bladder (OAB) circumstance. Material and method Pubic dataset acquisition was used to get ACE2 expression in normal human bladder and mice bladder (GSE129845). We built up over OAB model and studied the impact on cell typing and ACE2 expression. By way of using single-cell RNA sequencing (scRNA-seq) technique, bladder cell clustering and ACE2 expression in various cell types were measured respectively. Result In pubic database (healthy human and mice bladder), ACE2 expression in humans and mice is concentrated in bladder epithelial cells. The disappearance of umbrella cells, a component of bladder epithelial, was found in our OAB model. In the two mouse bladder samples, ACE2 expression of epithelial cells is 34.1%, also the highest of all cell types. Conclusion The disappearance of umbrella cell may alternate the infection pathway of 2019-nCov and relate to the onset and progression of OAB.

negative: Letter from the (un)seen virus: (post)humanist perspective in corona times

negative: This time is indeed different: A study on global market reactions to public health crisis() This paper studies the differences in stock market reactions to the same kind of disease-related news by analyzing abnormal returns of global stock markets during Public Health Risk Emergency of International Concern (PHEIC) announcements. Drawing the data from 26 stock market indices over the period from 22 April 2008 to 12 March 2020, we compare stock market reactions to all six PHEIC announcements made by the World Health Organization since 2009. Although the PHEIC announcements can be categorized as the same type of event, we found no consistent patterns in market reactions. The markets did not show significant reactions in a 30-day event window, which suggests a relatively low economic impact of the diseases on a global scale during this time, except for Covid-19. Among all diseases included in our study, only Covid-19 had a significant negative effect on stock markets at least lasting 30 days.

negative: Rapid diagnostic methods for acute viral respiratory infections

negative: Clinical Features of COVID-19 Related Liver Damage BACKGROUND: A recent outbreak of SARS-CoV-2 infection occurs mainly in China, with rapidly increasing the number of cases (namely COVID-19). Abnormal liver functions are frequently present in these patients, here we aimed to clarify the clinical features of COVID-19-related liver damage to provide some references for the clinical treatment. METHODS: In this retrospective, single-center study, we included all confirmed COVID-19 cases in Shanghai Public Health Clinical Center from January 20 to January 31, 2020. The outcomes were followed up until February 19, 2020. A total of 148 cases were analyzed for clinical features, laboratory parameters (including liver function tests), medications and the length of stay. FINDINGS: Of 148 confirmed SARS-CoV-2-infected patients, 49.3% were females and 50.7% were males. The median age was 50.5 years (interquartile range, 36-64). Patients had clinical manifestations of fever (70.1%), cough (45.3%), expectoration (26.7%) at admission. 75 patients (50.7%) showed abnormal liver functions at admission, characterized by an increased of alt, ast, GGT, AKP. Patients (n = 75) who had elevated liver function index were more likely to have a moderate-high degree fever (44% vs 27.4%; p = 0.035) and significantly present in male patients (62.67% vs 38.36%; p = 0.005). The numbers of CD4+ and CD8+ T cells were significantly lower in abnormal liver function group than those in normal liver function group. There was no statistical difference in prehospital medications between normal and abnormal liver function groups, while the utilization rate of lopinavir/ritonavir after admission was significantly higher in patients with emerging liver injury than that in patients with normal liver functions. Importantly, the emerging abnormal liver functions after admission caused a prolonged length of stay. INTERPRETATION: SARS-CoV-2 may cause the liver function damage and the Lopinavir/ritonavir should be applied carefully for the treatment of COVID-19.

negative: VIGOR, an annotation program for small viral genomes BACKGROUND: The decrease in cost for sequencing and improvement in technologies has made it easier and more common for the re-sequencing of large genomes as well as parallel sequencing of small genomes. It is possible to completely sequence a small genome within days and this increases the number of publicly available genomes. Among the types of genomes being rapidly sequenced are those of microbial and viral genomes responsible for infectious diseases. However, accurate gene prediction is a challenge that persists for decoding a newly sequenced genome. Therefore, accurate and efficient gene prediction programs are highly desired for rapid and cost effective surveillance of RNA viruses through full genome sequencing. RESULTS: We have developed VIGOR (Viral Genome ORF Reader), a web application tool for gene prediction in influenza virus, rotavirus, rhinovirus and coronavirus subtypes. VIGOR detects protein coding regions based on sequence similarity searches and can accurately detect genome specific features such as frame shifts, overlapping genes, embedded genes, and can predict mature peptides within the context of a single polypeptide open reading frame. Genotyping capability for influenza and rotavirus is built into the program. We compared VIGOR to previously described gene prediction programs, ZCURVE_V, GeneMarkS and FLAN. The specificity and sensitivity of VIGOR are greater than 99% for the RNA viral genomes tested. CONCLUSIONS: VIGOR is a user friendly web-based genome annotation program for five different viral agents, influenza, rotavirus, rhinovirus, coronavirus and SARS coronavirus. This is the first gene prediction program for rotavirus and rhinovirus for public access. VIGOR is able to accurately predict protein coding genes for the above five viral types and has the capability to assign function to the predicted open reading frames and genotype influenza virus. The prediction software was designed for performing high throughput annotation and closure validation in a post-sequencing production pipeline.

negative: An econometric analysis of SARS and Avian Flu on international tourist arrivals to Asia Abstract This paper compares the impacts of SARS and human deaths arising from Avian Flu on international tourist arrivals to Asia. The effects of SARS and human deaths from Avian Flu are compared directly according to the number of human deaths. The nature of the short run and long run relationship is examined empirically by estimating a static line fixed effect model and a difference transformation dynamic model, respectively. Empirical results from the static fixed effect and difference transformation dynamic models are consistent, and indicate that both the short run and long run SARS effect have a more significant impact on international tourist arrivals than does Avian Flu. In addition, the effects of deaths arising from both SARS and Avian Flu suggest that SARS is more important to international tourist arrivals than is Avian Flu. Thus, while Avian Flu is here to stay, its effect is currently not as significant as that of SARS.

negative: Study of knowledge, attitude, anxiety & perceived mental healthcare need in Indian population during COVID-19 pandemic Abstract Novel Corona Virus Disease (COVID-19) originating from China has rapidly crossed borders, infecting people throughout the whole world. This phenomenon has led to a massive public reaction; the media has been reporting continuously across borders to keep all informed about the pandemic situation. All these things are creating a lot of concern for people leading to heightened levels of anxiety. Pandemics can lead to heightened levels of stress; Anxiety is a common response to any stressful situation. This study attempted to assess the knowledge, attitude, anxiety experience, and perceived mental healthcare need among adult Indian population during the COVID-19 pandemic. An online survey was conducted using a semi-structured questionnaire using a non-probability snowball sampling technique. A total of 662 responses were received. The responders had a moderate level of knowledge about the COVID-19 infection and adequate knowledge about its preventive aspects. The attitude towards COVID-19 showed peoples' willingness to follow government guidelines on quarantine and social distancing. The anxiety levels identified in the study were high. More than 80 % of the people were preoccupied with the thoughts of COVID-19 and 72 % reported the need to use gloves, and sanitizers. In this study, sleep difficulties, paranoia about acquiring COVID-19 infection and distress related social media were reported in 12.5 %, 37.8 %, and 36.4 % participants respectively. The perceived mental healthcare need was seen in more than 80 % of participants. There is a need to intensify the awareness and address the mental health issues of people during this COVID-19 pandemic.

negative: Information sources and adoption of vaccine during pandemics PURPOSE: The purpose of this paper is to investigate the effects of different information sources on consumer health behavior during pandemics. DESIGN/METHODOLOGY/APPROACH: We collected survey data from 321 adults in a large western US city during November 2009 by mall and street intercepts. We analyzed their beliefs, attitudes and intentions with regard to adoption of the H1N1 (swine flu) vaccine. We developed and tested two alternative models on the role of mass media and personal information sources on the attitude towards the disease and the intention to get vaccinated. FINDINGS: Our study finds that mass media and personal sources of information simultaneously impact perceived threat from disease (attitude) and the intention to get vaccinated during a global pandemic. Personal information sources are more effective than mass media sources in impacting both attitude and intention. While the impact of mass media weakens from the attitude stage to the intention stage, the impact of personal information sources increases from the attitude stage to the intention stage. ORIGINALITY/VALUE: The contribution of this paper to health policy makers and marketers is to draw implications on how mass media and personal information sources could be better utilized to counter future global pandemics.

negative: Medical Anthropology Abstract Medical anthropology is an interdisciplinary subfield of anthropology with a long history of research on environmental health-related issues, especially those pertaining to human health within environments of risk, consequences of ecological degradation, and the way patterns of development and globalization impact environmental (and therefore human) health. In this article, the authors provide an introduction to the scope of medical anthropology research, its relevance to the field of environmental health, and the methods anthropologists use in their analyses. They conclude by elaborating on some of the key conceptual frameworks that guide current research and highlight topical areas in environmental health (broadly defined) where medical anthropology research is warranted.

negative: The complex associations of climate variability with seasonal influenza A and B virus transmission in subtropical Shanghai, China Abstract Most previous studies focused on the association between climate variables and seasonal influenza activity in tropical or temperate zones, little is known about the associations in different influenza types in subtropical China. The study aimed to explore the associations of multiple climate variables with influenza A (Flu-A) and B virus (Flu-B) transmissions in Shanghai, China. Weekly influenza virus and climate data (mean temperature (MeanT), diurnal temperature range (DTR), relative humidity (RH) and wind velocity (Wv)) were collected between June 2012 and December 2018. Generalized linear models (GLMs), distributed lag non-linear models (DLNMs) and regression tree models were developed to assess such associations. MeanT exerted the peaking risk of Flu-A at 1.4 °C (2-weeks’ cumulative relative risk (RR): 14.88, 95% confidence interval (CI): 8.67–23.31) and 25.8 °C (RR: 12.21, 95%CI: 6.64–19.83), Flu-B had the peak at 1.4 °C (RR: 26.44, 95%CI: 11.52–51.86). The highest RR of Flu-A was 23.05 (95%CI: 5.12–88.45) at DTR of 15.8 °C, that of Flu-B was 38.25 (95%CI: 15.82–87.61) at 3.2 °C. RH of 51.5% had the highest RR of Flu-A (9.98, 95%CI: 4.03–26.28) and Flu-B (4.63, 95%CI: 1.95–11.27). Wv of 3.5 m/s exerted the peaking RR of Flu-A (7.48, 95%CI: 2.73–30.04) and Flu-B (7.87, 95%CI: 5.53–11.91). DTR ≥ 12 °C and MeanT <22 °C were the key drivers for Flu-A and Flu-B, separately. The study found complex non-linear relationships between climate variability and different influenza types in Shanghai. We suggest the careful use of meteorological variables in influenza prediction in subtropical regions, considering such complex associations, which may facilitate government and health authorities to better minimize the impacts of seasonal influenza.

negative: Current and future antiviral therapy of severe seasonal and avian influenza The currently circulating H3N2 and H1N1 subtypes of influenza A virus cause a transient, febrile upper respiratory illness in most adults and children (“seasonal influenza”), but infants, the elderly, immunodeficient and chronically ill persons may develop life-threatening primary viral pneumonia or complications such as bacterial pneumonia. By contrast, avian influenza viruses such as the H5N1 virus that recently emerged in Southeast Asia can cause severe disease when transferred from birds to previously healthy people (“avian influenza”). Most H5N1 patients present with fever, cough and shortness of breath that progress rapidly to adult respiratory distress syndrome. In seasonal influenza, viral replication remains confined to the respiratory tract, but limited studies indicate that H5N1 infections are characterized by systemic viral dissemination, high cytokine levels and multiorgan failure. Gastrointestinal infection and encephalitis also occur. The licensed anti-influenza drugs (the M2 ion channel blockers, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir) are beneficial for uncomplicated seasonal influenza, but appropriate dosing regimens for severe seasonal or H5N1 viral infections have not been defined. Treatment options may be limited by the rapid emergence of drug-resistant viruses. Ribavirin has also been used to a limited extent to treat influenza. This article reviews approaches to therapy, including licensed drugs and treatments under development, including high-dose oseltamivir; parenterally administered neuraminidase inhibitors, peramivir and zanamivir; dimeric forms of zanamivir; the RNA polymerase inhibitor T-705; a ribavirin prodrug, viramidine; polyvalent and monoclonal antibodies; and combination therapies.

negative: Current Perspectives on Coronavirus Disease 2019 and Cardiovascular Disease: A White Paper by the JAHA Editors Coronavirus Disease 2019 (COVID-19) has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020. In this White Paper, we address the cardiovascular co-morbidities of COVID-19 infection; the diagnosis and treatment of standard cardiovascular conditions during the pandemic; and the diagnosis and treatment of the cardiovascular consequences of COVID-19 infection. In addition, we will also address various issues related to the safety of healthcare workers and the ethical issues related to patient care in this pandemic.

negative: Variable computed tomography appearances of COVID-19 The coronavirus disease 2019 (COVID-19) is typically diagnosed by specific assays that detect viral nucleic acid from the upper respiratory tract; however, this may miss infections involving only the lower airways. Computed tomography (CT) has been described as a diagnostic modality in the COVID-19 diagnosis and treatment plan. We present a case series with virologically confirmed COVID-19 pneumonia. Variable CT features were observed: consolidation with ground-glass opacities, ground-glass opacities with subpleural reticular bands, and an anterior-posterior gradient of lung abnormalities resembling that of acute respiratory distress syndrome. In one patient, we noted evolution of CT findings, where there was interval resolution of bilateral lung consolidation with development of bronchiolectasis and subpleural fibrotic bands. While sensitive for detecting lung parenchymal abnormalities in COVID-19 pneumonia, CT for initial diagnosis is discouraged and should be reserved for specific clinical indications. Interpretation of chest CT findings should be correlated with duration of symptoms to better determine the disease stage and aid in patient management.

negative: Avian influenza A (H5N1) Abstract Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have reached endemic levels among poultry in several southeast Asian countries and have caused a still increasing number of more than 100 reported human infections with high mortality. These developments have ignited global fears of an imminent influenza pandemic. The current knowledge of the virology, clinical spectrum, diagnosis and treatment of human influenza H5N1 virus infections is reviewed herein.

negative: Anti-IL6R role in treatment of COVID-19-related ARDS

negative: A large and accurate collection of peptidase cleavages in the MEROPS database Peptidases are enzymes that hydrolyse peptide bonds in proteins and peptides. Peptidases are important in pathological conditions such as Alzheimer's disease, tumour and parasite invasion, and for processing viral polyproteins. The MEROPS database is an Internet resource containing information on peptidases, their substrates and inhibitors. The database now includes details of cleavage positions in substrates, both physiological and non-physiological, natural and synthetic. There are 39 118 cleavages in the collection; including 34 606 from a total of 10 513 different proteins and 2677 cleavages in synthetic substrates. The number of cleavages designated as ‘physiological’ is 13 307. The data are derived from 6095 publications. At least one substrate cleavage is known for 45% of the 2415 different peptidases recognized in the MEROPS database. The website now has three new displays: two showing peptidase specificity as a logo and a frequency matrix, the third showing a dynamically generated alignment between each protein substrate and its most closely related homologues. Many of the proteins described in the literature as peptidase substrates have been studied only in vitro. On the assumption that a physiologically relevant cleavage site would be conserved between species, the conservation of every site in terms of peptidase preference has been examined and a number have been identified that are not conserved. There are a number of cogent reasons why a site might not be conserved. Each poorly conserved site has been examined and a reason postulated. Some sites are identified that are very poorly conserved where cleavage is more likely to be fortuitous than of physiological relevance. This data-set is freely available via the Internet and is a useful training set for algorithms to predict substrates for peptidases and cleavage positions within those substrates. The data may also be useful for the design of inhibitors and for engineering novel specificities into peptidases. Database URL: http://merops.sanger.ac.uk

negative: Association of national Bacille Calmette-Guerin vaccination policy with COVID-19 epidemiology: an ecological study in 78 countries A possible association between national Bacille Calmette-Guerin (BCG) vaccination policy and lower COVID-19 incidence has been suggested in some preprint papers. Using publicly accessible databases, I explored associations of national BCG vaccination policy with COVID-19 epidemiology in 78 countries. Data collection was conducted from April 25 to May 5, 2020. I compared countries that have a current universal BCG vaccination policy (BCG countries), with countries that currently lack such a policy (non-BCG countries). The mixed effect model revealed national BCG policy decreases in the country-specific risk of death by COVID-19, correspond to odds ratio of 0.446 (95% confidence intervals 0.323 - 0.614, P =1x10-5). In BCG countries, the case increase rate was attenuated marginally by 25.4% (95% CI 3.0 to 42.7, P=0.029) as compared with those of the non-BCG countries. Although the protective mechanism of BCG vaccination against COVID-19 remains unknown, further laboratory and clinical research should be warranted.

negative: SARS associated coronavirus has a recombinant polymerase and coronaviruses have a history of host-shifting Abstract The sudden appearance and potential lethality of severe acute respiratory syndrome associated coronavirus (SARS-CoV) in humans has focused attention on understanding its origins. Here, we assess phylogenetic relationships for the SARS-CoV lineage as well as the history of host-species shifts for SARS-CoV and other coronaviruses. We used a Bayesian phylogenetic inference approach with sliding window analyses of three SARS-CoV proteins: RNA dependent RNA polymerase (RDRP), nucleocapsid (N) and spike (S). Conservation of RDRP allowed us to use a set of Arteriviridae taxa to root the Coronaviridae phylogeny. We found strong evidence for a recombination breakpoint within SARS-CoV RDRP, based on different, well supported trees for a 5′ fragment (supporting SARS-CoV as sister to a clade including all other coronaviruses) and a 3′ fragment (supporting SARS-CoV as sister to group three avian coronaviruses). These different topologies are statistically significant: the optimal 5′ tree could be rejected for the 3′ region, and the optimal 3′ tree could be rejected for the 5′ region. We did not find statistical evidence for recombination in analyses of N and S, as there is little signal to differentiate among alternative trees. Comparison of phylogenetic trees for 11 known host-species and 36 coronaviruses, representing coronavirus groups 1–3 and SARS-CoV, based on N showed statistical incongruence indicating multiple host-species shifts for coronaviruses. Inference of host-species associations is highly sensitive to sampling and must be considered cautiously. However, current sampling suggests host-species shifts between mouse and rat, chicken and turkey, mammals and manx shearwater, and humans and other mammals. The sister relationship between avian coronaviruses and the 3′ RDRP fragment of SARS-CoV suggests an additional host-species shift. Demonstration of recombination in the SARS-CoV lineage indicates its potential for rapid unpredictable change, a potentially important challenge for public health management and for drug and vaccine development.

negative: COVID-19 and diabetes: Knowledge in progress AIMS: We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. METHODS: We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: "SARS-CoV-2", "COVID-19", "infection", "pathogenesis", "incubation period", "transmission", "clinical features", "diagnosis", "treatment", "diabetes", with interposition of the Boolean operator "AND". RESULTS: The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers or thiazolidinediones because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. CONCLUSIONS: Suggestions are made on the possible pathophysiological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.

negative: The psychological impact of COVID-19 pandemic on health care workers in a MERS-CoV endemic country BACKGROUND: The global pandemic of coronavirus disease of 2019 (COVID-19) has led to unprecedented psychological stress on health workers (HCWs). We aimed to assess the psychological impact of COVID-19 on HCWs in comparison to the stress brought on by the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in Saudi Arabia. METHOD: Between February 5th and 16th, 2020, 811 health-care workers (HCWs) of a tertiary care teaching hospital were invited to fill a questionnaire regarding concerns and worries about the novel coronavirus pandemic, along with Generalized Anxiety Disorder (GAD-7) Anxiety Severity screening tool. RESULTS: Out of 582 HCWs who completed the survey questionnaire (response rate of 71.8%), about 40% were exposed previously to MERS-CoV infected or suspected patients during a previous hospital outbreak. While there were no COVID-19 cases reported yet in Saudi Arabia at the time of data collection, still, the anxiety level from COVID-19 was significantly higher than that from MERS-CoV or seasonal influenza: 41.1% were more worried about COVID-19, 41.4% were similarly worried about both MERS-CoV and COVID-19, and 17.5% were more stressed by the previous MERS-CoV hospital outbreak. The most frequent concern was transmitting the infection to family and friends (2.71/5) than to themselves only (2.57/5). CONCLUSION: Pandemic and epidemic infectious diseases such as COVID-19 or MERS-CoV impose a significant level of anxiety and stress on healthcare workers who are caring of infected patients, with their main concern being the risk of transmitting the infection to their families or to acquire it themselves. Therefore, optimizing the compliance of healthcare workers with the proper infection prevention and control measures is paramount during the infectious disease outbreak, to ensure their safety, to decrease the likelihood of getting infected or transmitting the infection to others, and consequently to alleviate their psychological stress and anxiety.

negative: Pneumonia in the tropics Pneumonia in the tropics poses a heavy disease burden. The complex interplay of climate change, human migration influences and socio‐economic factors lead to changing patterns of respiratory infections in tropical climate but also increasingly in temperate countries. Tropical and poorer countries, especially South East Asia, also bear the brunt of the global tuberculosis (TB) pandemic, accounting for almost one‐third of the burden. But, as human migration patterns evolve, we expect to see more TB cases in higher income as well as temperate countries, and rise in infections like scrub typhus from ecotourism activities. Fuelled by the ease of air travel, novel zoonotic infections originating from the tropics have led to global respiratory pandemics. As such, clinicians worldwide should be aware of these new conditions as well as classical tropical bacterial pneumonias such as melioidosis. Rarer entities such as co‐infections of leptospirosis and chikungunya or dengue will need careful consideration as well. In this review, we highlight aetiologies of pneumonia seen more commonly in the tropics compared with temperate regions, their disease burden, variable clinical presentations as well as impact on healthcare delivery.

negative: Seasonality and uncertainty in COVID-19 growth rates The virus causing COVID-19 has spread rapidly worldwide and threatens millions of lives. It remains unknown if summer weather will reduce its continued spread, thereby alleviating strains on hospitals and providing time for vaccine development. Early insights from laboratory studies of related coronaviruses predicted that COVID-19 would decline at higher temperatures, humidity, and ultraviolet light. Using current, fine-scaled weather data and global reports of infection we developed a model that explained 36% of variation in early growth rates before intervention, with 17% based on weather or demography and 19% based on country-specific effects. We found that ultraviolet light was most strongly associated with lower COVID-19 growth rates. Projections suggest that, in the absence of intervention, COVID-19 will decrease temporarily during summer, rebound by autumn, and peak next winter. However, uncertainty remains high and the probability of a weekly doubling rate remained >20% throughout the summer in the absence of control. Consequently, aggressive policy interventions will likely be needed in spite of seasonal trends.

negative: Multivariate Analysis of Black Race and Environmental Temperature on COVID-19 In the US BACKGROUND: There has been much interest in environmental temperature and race as modulators of Coronavirus disease-19 (COVID-19) infection and mortality. However, in the United States race and temperature correlate with various other social determinants of health, comorbidities, and environmental influences that could be responsible for noted effects. This study investigates the independent effects of race and environmental temperature on COVID-19 incidence and mortality in United States counties. METHODS: Data on COVID-19 and risk factors in all United States counties was collected. 661 counties with at least 50 COVID-19 cases and 217 with at least 10 deaths were included in analyses. Upper and lower quartiles for cases/100,000 people and halves for deaths/100,000 people were compared with t-tests. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of race and environmental temperature. RESULTS: Multivariate regression analyses demonstrated Black race is a risk factor for increased COVID-19 cases (OR=1.22, 95% CI: 1.09-1.40, P=0.001) and deaths independent of comorbidities, poverty, access to health care, and other risk factors. Higher environmental temperature independently reduced caseload (OR=0.81, 95% CI: 0.71-0.91, P=0.0009), but not deaths. CONCLUSIONS: Higher environmental temperatures correlated with reduced COVID-19 cases, but this benefit does not yet appear in mortality models. Black race was an independent risk factor for increased COVID-19 cases and deaths. Thus, many proposed mechanisms through which Black race might increase risk for COVID-19, such as socioeconomic and healthcare-related predispositions, are inadequate in explaining the full magnitude of this health disparity.

negative: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24–3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.

negative: The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season Respiratory tract infection is a major cause of hospitalization in children. Although most such infections are viral in origin, it is difficult to differentiate bacterial and viral infections, as the clinical symptoms are similar. Multiplex polymerase chain reaction (PCR) methods allow testing for multiple pathogens simultaneously and are, therefore, gaining interest. This prospective case-control study was conducted from October 2013 to February 2014. Nasopharyngeal (NP) and oropharyngeal (throat) swabs were obtained from children admitted with severe acute respiratory infection (SARI) at a tertiary hospital. A control group of 40 asymptomatic children was included. Testing for 16 viruses was done by real-time multiplex PCR. Multiplex PCR detected a viral pathogen in 159/177 (89.9 %) patients admitted with SARI. There was a high rate of co-infection (46.9 %). Dual detections were observed in 64 (36.2 %), triple detections in 17 (9.6 %), and quadruple detections in 2 (1.1 %) of 177 samples. Seventy-eight patients required intensive care unit (ICU) admission, of whom 28 (35.8 %) had co-infection with multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected among asymptomatic children. This study confirms the high rate of detection of viral nucleic acids by multiplex PCR among hospitalized children admitted with SARI, as well as the high rate of co-detection of multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected in asymptomatic children, resulting in challenges in clinical interpretation. Studies are required to provide quantitative conclusions that will facilitate clinical interpretation and application of the results in the clinical setting.

negative: Initial psychological responses to Influenza A, H1N1 ("Swine flu") BACKGROUND: The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 ("Swine flu") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. METHODS: 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption RESULTS: 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. CONCLUSION: Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food. Discussions with family and friends may reinforce existing anxiety levels. Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic. Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation.

negative: Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis BACKGROUND: Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses invoke several common host response pathways. Further analysis of these pathways suggests potential opportunities for therapeutic intervention.

negative: Hematological findings and complications of COVID‐19 COVID‐19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL‐6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID‐19 patients. Elevated D‐Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life‐threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID‐19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.

negative: VIRAL ETIOLOGY AND OUTCOME OF SEVERE LOWER RESPIRATORY TRACT INFECTIONS AMONG CRITICALLY ILL CHILDREN ADMITTED TO THE PICU ABSTRACT Objective: To determine the viral etiology of severe lower respiratory tract infections (LRTIs), their clinical significance and prognosis among critically ill children. Design: A prospective descriptive study was carried out. Setting: Pediatric Intensive Care Unit (PICU) of Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey. Patients: A total of 115 patients hospitalized in the PICU were evaluated for inclusion in the study. Children with underlying comorbidities and those who did not require mechanical ventilation were excluded. Main variables of interest: Demographic, clinical, laboratory test and radiographic data were recorded. Results: A total of 63 patients were eligible for the study. The most common diagnosis was bronchiolitis (57.1%). Respiratory syncytial virus (RSV) was the most frequent causal virus (36.5%). The most common complication was acute respiratory distress syndrome (ARDS) (28.6%). Multiple viral infection was identified in 20.6% of the patients, the most common in this subgroup being rhinovirus. Patients with bocavirus infection had a higher likelihood of needing invasive mechanical ventilation (IMV) at presentation. Children who died were likely to be < 12 months old, have ARDS, hepatitis, pneumomediastinum, multiple viral infection, and required IMV support with an increased duration of MV. Additionally, they were found to have a high Pediatric Risk of Mortality III score, Predicted Death Rate and increased need for inotropic support at admission. Conclusions: Our study showed critically ill children with LRTI without known risk factors to have high mortality when aged < 12 months, in the presence of multiple agents and when certain complications (ARDS, hepatitis) and X-ray findings were identified.

negative: Epidemic prevention and control measures in China significantly curbed the epidemic of COVID-19 and influenza At the end of 2019, an outbreak of unknown pathogen pneumonia occurred in China, then it was named corona virus disease 2019 (COVID-19). With the rapid spread of COVID-19, a series of strict prevention and control measures were implemented to cut the spread of the epidemic. Influenza as a respiratory tract infection disease as COVID-19 might also be controlled. To assess the effects, we used the total passenger numbers sent in mainland China from 2018 to 2020 and the daily number of railway passenger (DNRP) flow in 2020 during Spring Festival travel rush to reflect the population movement and further to analyze newly and cumulative confirmed COVID-19 and influenza. We found that with implementing the series measures on COVID-19, not only COVID-19, but also influenza mitigated in China. The prevention and control measures for COVID-19 might be used in controlling respiratory tract diseases, and reducing the national health economic burden. When other countries issue measures on COVID-19 and influenza, they should consider adopting more aggressive epidemic prevention and control strategies.

negative: Novel Coronavirus (COVID-19): Leveraging Telemedicine to Optimize Care While Minimizing Exposures and Viral Transmission

negative: Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying high-risk comorbidities in a paediatric population Background: There is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social shielding (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Childrens Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities. Methods: Routine clinical data were extracted retrospectively from the Institutions Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance. Findings: Between 1st March and 15th May 2020, 166 children (<18 years of age) presented to a specialist childrens hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9-14] years vs median 1 [0.1-5.7.5] years respectively, p<0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p=0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p<0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p=0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population. Interpretation: COVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing COVID-19 vulnerable medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented.

negative: Using ILI surveillance to estimate state-specific case detection rates and forecast SARS-CoV-2 spread in the United States Detection of SARS-CoV-2 infections to date has relied on RT-PCR testing. However, a failure to identify early cases imported to a country, bottlenecks in RT-PCR testing, and the existence of infections which are asymptomatic, sub-clinical, or with an alternative presentation than the standard cough and fever have resulted in an under-counting of the true prevalence of SARS-CoV-2. Here, we show how publicly available CDC influenza-like illness (ILI) outpatient surveillance data can be repurposed to estimate the detection rate of symptomatic SARS-CoV-2 infections. We find a surge of non-influenza ILI above the seasonal average and show that this surge is correlated with COVID case counts across states. By quantifying the number of excess ILI patients in March relative to previous years and comparing excess ILI to confirmed COVID case counts, we estimate the syndromic case detection rate of SARS-CoV-2 in the US to be less than 13%. If only 1/3 of patients infected with SARS-CoV-2 sought care, the ILI surge would correspond to more than 8.7 million new SARS-CoV-2 infections across the US during the three week period from March 8 to March 28. Combining excess ILI counts with the date of onset of community transmission in the US, we also show that the early epidemic in the US was unlikely to be doubling slower than every 4 days. Together these results suggest a conceptual model for the COVID epidemic in the US in which rapid spread across the US are combined with a large population of infected patients with presumably mild-to-moderate clinical symptoms. We emphasize the importance of testing these findings with seroprevalence data, and discuss the broader potential to use syndromic time series for early detection and understanding of emerging infectious diseases.

negative: COVID-19: time for paradigm shift in the nexus between local, national and global health

negative: Seasonal Influenza Vaccination and the Heightened Risk of Coronavirus and Other Pandemic Virus Infections: Fact or Fiction?

negative: Review of practical recommendations for otolaryngologists and head and neck surgeons during the COVID-19 pandemic: Recommendations for otolaryngologists during the COVID-19 pandemic INTRODUCTION: Otolaryngologists are at very high risk of COVID-19 infection while performing examination or surgery. Strict guidelines for these specialists have not already been provided, while currently available recommendations could presumably change in course of COVID-19 pandemic as the new data increases. OBJECTIVES: This study aimed to synthesize evidence concerning otolaryngology during COVID‐19 pandemic. It presents a review of currently existing guidelines and recommendations concerning otolaryngological procedures and surgeries during COVID-19 pandemic, and provides a collective summary of all crucial information for otolaryngologists. It summarizes data concerning COVID-19 transmission, diagnosis, and clinical presentation highlighting the information significant for otolaryngologists. METHODS: The Medline and Web of Science databases were searched without time limit using terms ‘‘COVID-19”, “SARS-CoV-2” in conjunction with “head and neck surgery”, “otorhinolaryngological manifestations”. RESULTS: Patients in stable condition should be consulted using telemedicine options. Only emergency consultations and procedures should be performed during COVID-19 pandemic. Mucosa-involving otolaryngologic procedures are considered high risk procedures and should be performed using enhanced PPE (N95 respirator and full face shield or powered air-purifying respirator, disposable gloves, surgical cap, gown, shoe covers). Urgent surgeries for which there is not enough time for SARS-CoV-2 screening are also considered high risk procedures. These operations should be performed in a negative pressure operating room with high-efficiency particulate air filtration. Less urgent cases should be tested for COVID-19 twice, 48 hours preoperatively in 24 hours’ interval. CONCLUSIONS: This review serves as a collection of current recommendations for otolaryngologists for how to deal with their patients during COVID-19 pandemic.

negative: Patterns of mortality during pandemic: An example of Spanish flu pandemic of 1918 Now the attention of the whole world is focused on the developing pandemic of the coronavirus infection COVID-19. This article discusses mortality patterns of the deadliest epidemic in the last 120 years – the Spanish flu pandemic of 1918. Statistical sources from Italy and the USA, published shortly after the pandemic, were analyzed. The analysis was carried out for mortality from all causes, since in this case inaccuracies associated with establishing the causes of death are minimized. Despite the fact that the first cases of the Spanish flu appeared in the United States as early as March 1918, this first wave of epidemic practically did not affect the total mortality rate. The main peak of mortality in 1918 occurred in October 1918 both in the USA and Italy, with a gradual decrease in mortality over several months. Analysis of age-specific mortality demonstrates a significant increase in mortality at middle ages (20–50 years) in 1918 compared with 1917. Analysis of mortality trends using the method of latent variables shows a significant increase in the background mortality factor in 1918, which turned out to be higher for Italy than the mortality losses during the Second World War. The Spanish flu pandemic differs from the current coronavirus pandemic, because of significant increase in mortality of middle-aged people, while the COVID-19 pandemic causes a more marked increase in mortality among the elderly. With this, the COVID-19 pandemic is more like the recent flu epidemics than the earlier Spanish flu pandemic.

negative: Insights into the June 2020 Issue of the JOE

negative: Anticipation and response: pandemic influenza in Malawi, 2009 Background: In 2006, Malawi developed a national influenza plan to mitigate, prevent and manage the burden of infection should an outbreak occur. In 2009, it translated its contingency plan to respond to the unfolding influenza pandemic. However, little is known of how Malawi translated its national influenza plan into response actions, or the success of these responses. Objective: To investigate how Malawi translated its preparedness plan and so broaden our understanding of the outcomes of the responses. Methods: We draw on data from 22 in-depth interviews with government policymakers and people working at a policy level in various non-governmental organisations, conducted to assess the level of preparedness and the challenges of translating this. Results: Through a number of public health initiatives, authorities developed communication strategies, strengthened influenza surveillance activities and updated overall goals in pandemic training and education. However, without influenza drills, exercises and simulations to test the plan, activating the pandemic plan, including coordinating and deploying generic infection control measures, was problematic. Responses during the pandemic were at times ‘weak and clumsy’ and failed to mirror the activities and processes highlighted in the preparedness plan. Conclusions: Participants stressed that in order to achieve a coordinated and successful response to mitigate and prevent the further transmission of pandemic influenza, good preparation was critical. The key elements which they identified as relevant for a rapid response included effective communications, robust evidence-based decision-making, strong and reliable surveillance systems and flexible public health responses. To effectively articulate a viable trajectory of pandemic responses, the potential value of simulation exercises could be given more consideration as a mean of sustaining good levels of preparedness and responses against future pandemics. These all demand a well-structured planning for and response to pandemic influenza strategy developed by a functioning scientific and policy advisory committee.

negative: Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate forCOVID-19: Meta-analysis and sensitivity analysis The coronavirus disease 2019 (COVID-19) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensive knowledge of COVID-19 remains incomplete and many important features are still unknown. This manuscripts conduct a meta-analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% interval (2.41, 3.90), the average incubation time to be 5.08 days with the 95% confidence interval (4.77, 5.39) (in day), the asymptomatic infection rate to be 46% with the 95% confidence interval (18.48%, 73.60%), and the case fatality rate to be 2.72% with 95% confidence interval (1.29%, 4.16%) where asymptomatic infections are accounted for.

negative: Still puzzling questions in immunology (infection and immunity)

negative: Timely tale of avian flu A gripping account of the spread of the bird flu virus across southeast Asia holds lessons for the global management of pandemics such as swine flu, explains Ab Osterhaus.

negative: Analysis clinical features of COVID-19 infection in secondary epidemic area and report potential biomarkers in evaluation Objective: Based on the clinical characteristics of infected patients with novel coronavirus in secondary epidemic areas,we aimed to identify potential biomarkers for the evaluation of novel coronavirus-infected patients,guide the diagnosis and treatment of this disease in secondary epidemic areas and provide a reference for the clinical prevention and control of this epidemic situation. Methods: The clinical data of 33 patients with respiratory symptoms caused by the novel coronavirus in Wenzhou city from January 15 to February 12,2020,were thoroughly reviewed. At the onset of the disease,we found that the primary symptoms were fever,cough,fatigue,chest tightness,chest pain and specific blood test results. According to the patients'histories,the patients were divided into two groups: those who spent time in the main epidemic area and those who did not spend time in the main epidemic area. The differences in the clinical manifestations between these two groups were analyzed. Results: The main clinical symptoms of patients infected with novel coronavirus in the secondary epidemic area were respiratory tract ailments and systemic symptoms. After grouping patients based on the presence or absence of residency in or travel history to the main epidemic area, there was no significant difference between the baseline data of these two groups, and there were no significant differences in symptoms and signs between the two groups (P>0.05). Some patients had abnormally increased serum amyloid protein A (SAA). There were statistically significant differences in the leukocyte count/C-reactive protein,monocyte ratio/C-reactive protein,neutrophil count/C-reactive protein,monocyte count/C-reactive protein and hemoglobin/C-reactive protein values between the two groups (P < 0.05). Conclusion: Respiratory tract ailments and systemic symptoms were the primary symptoms of novel coronavirus infection in the secondary epidemic area; these symptoms are not typical. The abnormal increase in serum amyloid protein (SAA) may be used as an auxiliary index for diagnosis and treatment. CRP changes before other blood parameters and thus may be an effective evaluation index for patients with COVID-19 infection.

negative: Co-infection with Influenza Viruses and Influenza-Like Virus During the 2015/2016 Epidemic Season Concerning viral infection of the respiratory system, a single virus can cause a variety of clinical symptoms and the same set of symptoms can be caused by different viruses. Moreover, infection is often caused by a combination of viruses acting at the same time. The present study demonstrates, using multiplex RT-PCR and real-time qRT-PCR, that in the 2015/2016 influenza season, co-infections were confirmed in patients aged 1 month to 90 years. We found 73 co-infections involving influenza viruses, 17 involving influenza viruses and influenza-like viruses, and six involving influenza-like viruses. The first type of co-infections above mentioned was the most common, amounting to 51 cases, with type A and B viruses occurring simultaneously. There also were four cases of co-infections with influenza virus A/H1N1/pdm09 and A/H1N1/ subtypes and two cases with A/H1N1/pdm09 and A/H3N2/ subtypes. The 2015/2016 epidemic season was characterized by a higher number of confirmed co-infections compared with the previous seasons. Infections by more than one respiratory virus were most often found in children and in individuals aged over 65.

negative: Chapter 6 The immunosuppressed traveler: infection risks with autoimmunity and immunosuppression, vaccinations, and general travel advice Abstract The travel-related infection risks in the significantly immunocompromised traveler are complex and comprise vaccine preventable, vector-borne, and other nonvaccine preventable infections. A thorough risk assessment should be performed before travel and advice sought from relevant specialists. Immunosuppression used to treat autoimmune diseases and their mechanisms of action need particular consideration.This risk assessment needs to take the patient's beliefs and preferences into account. It is also important not to neglect noninfectious travel considerations.

negative: Making sense of the Global Coronavirus Data: The role of testing rates in understanding the pandemic and our exit strategy The Coronavirus disease 2019(COVID-19) outbreak has caused havoc across the world. Subsequently, research on COVID-19 has focused on number of cases and deaths and predicted projections have focused on these parameters. We propose that the number of tests performed is a very important denominator in understanding the COVID-19 data. We analysed the number of diagnostic tests performed in proportion to the number of cases and subsequently deaths across different countries and projected pandemic outcomes. We obtained real time COVID-19 data from the reference website Worldometer at 0900 BST on Saturday 4th April, 2020 and collated the information obtained on the top 50 countries with the highest number of COVID 19 cases. We analysed this data according to the number of tests performed as the main denominator. Country wise population level pandemic projections were extrapolated utilising three models - 1) inherent case per test and death per test rates at the time of obtaining the data (4/4/2020 0900 BST) for each country; 2) rates adjusted according to the countries who conducted at least 100000 tests and 3) rates adjusted according to South Korea. We showed that testing rates impact on the number of cases and deaths and ultimately on future projections for the pandemic across different countries. We found that countries with the highest testing rates per population have the lowest death rates and give us an early indication of an eventual COVID-19 mortality rate. It is only by continued testing on a large scale that will enable us to know if the increasing number of patients who are seriously unwell in hospitals across the world are the tip of the iceberg or not. Accordingly, obtaining this information through a rapid increase in testing globally is the only way which will enable us to exit the COVID-19 pandemic and reduce economic and social instability.

negative: COVID-19: Should We Test Everyone? Since the beginning of 2020, the coronavirus disease 2019 (COVID-19) has spread rapidly in the city of Wuhan, P.R. China, and subsequently, across the world. The swift spread of the virus is largely attributed to its stealth transmissions in which infected patients may be asymptomatic. Undetected transmissions present a remarkable challenge for the containment of the virus and pose an appalling threat to the public. An urgent question that has been asked by the public is"Should I be tested for COVID-19 if I am sick?". While different regions established their own criteria for screening infected cases, the screening criteria have been modified based on new evidence and understanding of the virus as well as the availability of resources. The shortage of test kits and medical personnel has considerably limited our ability to do as many tests as possible. Public health officials and clinicians are facing a dilemma of balancing the limited resources and unlimited demands. On one hand, they are striving to achieve the best outcome by optimizing the usage of the scant resources. On the other hand, they are challenged by the patients' frustrations and anxieties, stemming from the concerns of not being tested for COVID-19 for not meeting the definition of PUI (person under investigation). In this paper, we evaluate the situation from the statistical viewpoint by factoring into the considerations of the uncertainty and inaccuracy of the test, an issue that is often overlooked by the general public. We aim to shed light on the tough situation by providing evidence-based reasoning from the statistical angle, and we expect this examination will help the general public understand and assess the situation rationally. Most importantly, the development offers recommendations for physicians to make sensible evaluations to optimally use the limited resources for the best medical outcome.

negative: Prediction of New Coronavirus Infection Based on a Modified SEIR Model BACKGROUND The outbreak of the new coronavirus infection in Wuhan City, Hubei Province in December 2019, poses a huge threat to China and even global public health security. Respiratory droplets and contact transmission are the main routes of transmission of new coronaviruses. Compared with SARS and Ebola viruses, new coronavirus infections are infectious during the incubation period. Traditional SEIR (susceptibility-exposure-infection-Removal) There are some differences in conditions for the prediction of the epidemic trend of new coronavirus infection. The outbreak of the new coronavirus infection coincided with the Spring Festival before and after the Chinese Spring Festival.It is necessary to make appropriate optimization and amendments to the traditional model to meet the actual evolution of the epidemic situation. METHODS The traditional SEIR model assumes that the virus-infected person is not infectious during the incubation period and that the infected person did not take isolation measures during the illness. The transmission of the new coronavirus no longer meets the basic assumptions of the classical kinetic system. Therefore, this article first establishes a modified SEIR model. Predict and analyze the changing trend of the epidemic situation, then estimate the parameters involved in the infection dynamics model, and then use Matlab to simulate the established dynamic equations based on public data and analyze the results. Recommendations for universal prevention and control of infectious diseases. RESULTS The first case of new coronavirus infection was confirmed in Wuhan on December 8, 2019. When Wuhan City took no action, assuming the average daily number of contacts per infected person k = 5, the number of infected persons will reach about 2,384,803 people; If wuhan adopts the measures of sealing the city on January 22, 2020, under the premise of k=2, the number of infected people decreases by 19,773 compared with that on January 23, and there is no significant change in the time when the number of infected people reaches the peak. Under the premise of k = 1, the number of infected persons was reduced by 14,330 compared with the closure on January 23, and the time to reach the peak of the number of infected persons was reduced by 2 days. If Wuhan City is closed for one day, the number of infected persons will increase from 106,145 to 130,626 under the premise of k = 2; the number of infected persons will increase from 74,369 to 92,010 under the premise of k = 1. CONCLUSIONS Comparing the number of confirmed diagnoses actually notified by the department with the number of infected people obtained from the simulation of the model, it can be seen that the city closure measures adopted by the Wuhan Municipal Government on January 23 and the first-level response measures adopted by the country are effective for the epidemic Prevention and control play a vital role. Wearing a mask when going out and avoiding close contact with people can effectively reduce the infection rate.

negative: DNA Vaccines against Protozoan Parasites: Advances and Challenges Over the past 15 years, DNA vaccines have gone from a scientific curiosity to one of the most dynamic research field and may offer new alternatives for the control of parasitic diseases such as leishmaniasis and Chagas disease. We review here some of the advances and challenges for the development of DNA vaccines against these diseases. Many studies have validated the concept of using DNA vaccines for both protection and therapy against these protozoan parasites in a variety of mouse models. The challenge now is to translate what has been achieved in these models into veterinary or human vaccines of comparable efficacy. Also, genome-mining and new antigen discovery strategies may provide new tools for a more rational search of novel vaccine candidates.

negative: Severe Childhood Respiratory Viral Infections

negative: School absenteeism among school‐aged children with medically attended acute viral respiratory illness during three influenza seasons, 2012‐2013 through 2014‐2015 BACKGROUND: Acute respiratory illnesses (ARIs) are common in school‐aged children, but few studies have assessed school absenteeism due to specific respiratory viruses. OBJECTIVE: To evaluate school absenteeism among children with medically attended ARI due to common viruses. METHODS: We analyzed follow‐up surveys from children seeking care for acute respiratory illness who were enrolled in the influenza vaccine effectiveness study at Marshfield Clinic during the 2012‐2013 through 2014‐2015 influenza seasons. Archived influenza‐negative respiratory swabs were retested using multiplex RT‐PCR to detect 16 respiratory virus targets. Negative binomial and logistic regression models were used to examine the association between school absence and type of respiratory viruses; endpoints included mean days absent from school and prolonged (>2 days) absence. We examined the association between influenza vaccination and school absence among children with RT‐PCR‐confirmed influenza. RESULTS: Among 1027 children, 2295 days of school were missed due to medically attended ARIs; influenza accounted for 39% of illness episodes and 47% of days missed. Mean days absent were highest for influenza (0.96‐1.19) and lowest for coronavirus (0.62). Children with B/Yamagata infection were more likely to report prolonged absence than children with A/H1N1 or A/H3N2 infection [OR (95% CI): 2.1 (1.0, 4.5) and 1.7 (1.0, 2.9), respectively]. Among children with influenza, vaccination status was not associated with prolonged absence. CONCLUSIONS: School absenteeism due to medically attended ARIs varies by viral infection. Influenza B infections accounted for the greatest burden of absenteeism.

negative: Prospective and retrospective evaluation of the Cepheid Xpert® Flu/RSV XC assay for rapid detection of influenza A, influenza B, and respiratory syncytial virus Abstract A total of 281 clinical specimens (nasal swabs and nasopharyngeal aspirates) were tested with the Xpert® Flu/RSV XC. The results were compared to those obtained with the real-time retro transcriptase-polymerase chain reaction assays routinely used in our laboratory. The Xpert® Flu/RSV XC showed sensitivity/specificity of 97.8%/100% and 97.9%/100% for flu and respiratory syncytial virus, respectively.

negative: Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as ‘Public Health Emergency of International Concern’ on January 30(th), 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.

negative: The assessment of data sources for influenza virologic surveillance in New York State BACKGROUND: Following the 2013 USA release of the Influenza Virologic Surveillance Right Size Roadmap, the New York State Department of Health (NYSDOH) embarked on an evaluation of data sources for influenza virologic surveillance. OBJECTIVE: To assess NYS data sources, additional to data generated by the state public health laboratory (PHL), which could enhance influenza surveillance at the state and national level. METHODS: Potential sources of laboratory test data for influenza were analyzed for quantity and quality. Computer models, designed to assess sample sizes and the confidence of data for statistical representation of influenza activity, were used to compare PHL test data to results from clinical and commercial laboratories, reported between June 8, 2013 and May 31, 2014. RESULTS: Sample sizes tested for influenza at the state PHL were sufficient for situational awareness surveillance with optimal confidence levels, only during peak weeks of the influenza season. Influenza data pooled from NYS PHLs and clinical laboratories generated optimal confidence levels for situational awareness throughout the influenza season. For novel influenza virus detection in NYS, combined real‐time (rt) RT‐PCR data from state and regional PHLs achieved ≥85% confidence during peak influenza activity, and ≥95% confidence for most of low season and all of off‐season. CONCLUSIONS: In NYS, combined data from clinical, commercial, and public health laboratories generated optimal influenza surveillance for situational awareness throughout the season. Statistical confidence for novel virus detection, which is reliant on only PHL data, was achieved for most of the year.

negative: Large-scale evolutionary surveillance of the 2009 H1N1 influenza A virus using resequencing arrays In April 2009, a new influenza A (H1N1 2009) virus emerged that rapidly spread around the world. While current variants of this virus have caused widespread disease, particularly in vulnerable groups, there remains the possibility that future variants may cause increased virulence, drug resistance or vaccine escape. Early detection of these virus variants may offer the chance for increased containment and potentially prevention of the virus spread. We have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components and mutation hotspots. The accompanying base-calling software (EvolSTAR) introduces novel methods that utilize neighbourhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries. Our results demonstrate that EvolSTAR is highly accurate and has a much improved call rate. The high throughput and short turn-around time from sample to sequence and analysis results (30 h for 24 samples) makes this kit an efficient large-scale evolutionary biosurveillance tool.

negative: COVID-19 Pandemia and Public and Global Mental Health from the Perspective of Global Health Securit. The Coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China and has spread all over the world and has caused huge threats to health and lives. It has affected different frontiers of lives and induced many psychiatric individual and collective problems such as panic, anxiety, depression, post-traumatic stress disorders, suspiciousness, infodemia, cacophony, xenophobia, racisms, etc. The COVID-19 outbreak has induced public and global mental health crisis as well as a huge psycho-social experiment. Psychiatry and other mental health sciences can play very useful role in supporting the well-being of COVID-19 patients and their families, healthcare personnel and the society. For successful fighting with present and future pandemics we have to learn more about psychiatric and psychological aspects of COVID-19 from the perspectives of public and global mental health.

negative: Genomic, geographic and temporal distributions of SARS-CoV-2 mutations The COVID-19 pandemic is the most significant public health issue in recent history. Its causal agent, SARS-CoV-2, has evolved rapidly since its first emergence in December 2019. Mutations in the viral genome have critical impacts on the adaptation of viral strains to the local environment, and may alter the characteristics of viral transmission, disease manifestation, and the efficacy of treatment and vaccination. Using the complete sequences of 1,932 SARS-CoV-2 genomes, we examined the genomic, geographic and temporal distributions of aged, new, and frequent mutations of SARS-CoV-2, and identified six phylogenetic clusters of the strains, which also exhibit a geographic preference in different continents. Mutations in the form of single nucleotide variations (SNVs) provide a direct interpretation for the six phylogenetic clusters. Linkage disequilibrium, haplotype structure, evolutionary process, global distribution of mutations unveiled a sketch of the mutational history. Additionally, we found a positive correlation between the average mutation count and case fatality, and this correlation had strengthened with time, suggesting an important role of SNVs on disease outcomes. This study suggests that SNVs may become an important consideration in virus detection, clinical treatment, drug design, and vaccine development to avoid target shifting, and that continued isolation and sequencing is a crucial component in the fight against this pandemic. Significance Statement Mutation is the driving force of evolution for viruses like SARS-CoV-2, the causal agent of COVID-19. In this study, we discovered that the genome of SARS-CoV-2 is changing rapidly from the originally isolated form. These mutations have been spreading around the world and caused more than 2.5 million of infected cases and 170 thousands of deaths. We found that fourteen frequent mutations identified in this study can characterize the six main clusters of SARS-CoV-2 strains. In addition, we found the mutation burden is positively correlated with the fatality of COVID-19 patients. Understanding mutations in the SARS-CoV-2 genome will provide useful insight for the design of treatment and vaccination.

negative: Metagenomic analysis of viral nucleic acid extraction methods in respiratory clinical samples BACKGROUND: Numerous protocols for viral enrichment and genome amplification have been created. However, the direct identification of viral genomes from clinical specimens using next-generation sequencing (NGS) still has its challenges. As a selected viral nucleic acid extraction method may determine the sensitivity and reliability of NGS, it is still valuable to evaluate the extraction efficiency of different extraction kits using clinical specimens directly. RESULTS: In this study, we performed qRT-PCR and viral metagenomic analysis of the extraction efficiency of four commonly used Qiagen extraction kits: QIAamp Viral RNA Mini Kit (VRMK), QIAamp MinElute Virus Spin Kit (MVSK), RNeasy Mini Kit (RMK), and RNeasy Plus Micro Kit (RPMK), using a mixed respiratory clinical sample without any pre-treatment. This sample contained an adenovirus (ADV), influenza virus A (Flu A), human parainfluenza virus 3 (PIV3), human coronavirus OC43 (OC43), and human metapneumovirus (HMPV). The quantity and quality of the viral extracts were significantly different among these kits. The highest threshold cycle(Ct)values for ADV and OC43 were obtained by using the RPMK. The MVSK had the lowest Ct values for ADV and PIV3. The RMK revealed the lowest detectability for HMPV and PIV3. The most effective rate of NGS data at 67.47% was observed with the RPMK. The other three kits ranged between 12.1–26.79% effectiveness rates for the NGS data. Most importantly, compared to the other three kits the highest proportion of non-host reads was obtained by the RPMK. The MVSK performed best with the lowest Ct value of 20.5 in the extraction of ADV, while the RMK revealed the best extraction efficiency by NGS analysis. CONCLUSIONS: The evaluation of viral nucleic acid extraction efficiency is different between NGS and qRT-PCR analysis. The RPMK was most applicable for the metagenomic analysis of viral RNA and enabled more sensitive identification of the RNA virus genome in respiratory clinical samples. In addition, viral RNA extraction kits were also applicable for metagenomic analysis of the DNA virus. Our results highlighted the importance of nucleic acid extraction kit selection, which has a major impact on the yield and number of viral reads by NGS analysis. Therefore, the choice of extraction method for a given viral pathogen needs to be carefully considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5152-5) contains supplementary material, which is available to authorized users.

negative: Influenza A H1N1 2009 (Swine Flu) and Pregnancy The Influenza A H1N1 pandemic (A H1N1) occurred between June 2009 and August 2010. Although the pandemic is now over, the virus has emerged as the predominant strain in the current seasonal influenza phase in the northern hemisphere. The A H1N1 influenza is a novel strain of the influenza A virus and is widely known as swine flu. The virus contains a mixture of genetic material from human, pig and bird flu virus. It is a new variety of flu which people have not had much immunity to. Much has been learnt from the Pandemic of 2009/2010 but the messages about vaccination and treatment seem to be taken slowly by the clinical profession. Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery. The median duration of illness is around seven days. This influenza typically affects the younger age group i.e. from the ages of 5–65 years. Current experience shows that the age group experiencing increased morbidity and mortality rates are in those under 65 years of age. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters. In the United Kingdom, twelve maternal deaths were reported to be associated with the H1N1 virus during the pandemic and clear avoidable factors were identified (Modder, Review of Maternal Deaths in the UK related to A H1N1 2009 influenza (CMACE). www.cmace.org.uk, 2010). The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate (Yates et al. Health Technol Assess 14(34):109–182, 2010). There continues to be a low uptake of the flu vaccine and commencement of antiviral treatment for pregnant women.

negative: Underlying trend, seasonality, prediction, forecasting and the contribution of risk factors: an analysis of globally reported cases of Middle East Respiratory Syndrome Coronavirus This study set out to identify and analyse trends and seasonal variations of monthly global reported cases of the Middle East respiratory syndrome coronavirus (MERS-CoV). It also made a prediction based on the reported and extrapolated into the future by forecasting the trend. Finally, the study assessed contributions of various risk factors in the reported cases. The motivation for this study is that MERS-CoV remains among the list of blueprint priority and potential pandemic diseases globally. Yet, there is a paucity of empirical literature examining trends and seasonality as the available evidence is generally descriptive and anecdotal. The study is a time series analysis using monthly global reported cases of MERS-CoV by the World Health Organisation between January 2015 and January 2018. We decomposed the series into seasonal, irregular and trend components and identified patterns, smoothened series, generated predictions and employed forecasting techniques based on linear regression. We assessed contributions of various risk factors in MERS-CoV cases over time. Successive months of the MERS-CoV cases suggest a significant decreasing trend (P = 0.026 for monthly series and P = 0.047 for Quarterly series). The MERS-CoV cases are forecast to wane by end 2018. Seasonality component of the cases oscillated below or above the baseline (the centred moving average), but no association with the series over time was noted. The results revealed contributions of risk factors such as camel contact, male, old age and being from Saudi Arabia and Middle East regions to the overall reported cases of MERS-CoV. The trend component and several risk factors for global MERS-CoV cases, including camel contact, male, age and geography/region significantly affected the series. Our statistical models appear to suggest significant predictive capacity and the findings may well inform healthcare practitioners and policymakers about the underlying dynamics that produced the globally reported MERS-CoV cases.

negative: Will COVID-19 pandemic diminish by summer-monsoon in India? Lesson from the first lockdown The novel Coronavirus (2019-nCoV) was identified in Wuhan, Hubei Province, China, in December 2019 and has created a medical emergency worldwide. It has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization. In India, it is already reported more than 18 thousand cases and more than 600 deaths due to Coronavirus disease 2019 (COVID-19) till April 20, 2020. Previous studies on various viral infections like influenza have supported an epidemiological hypothesis that the cold and dry (low absolute humidity) environments favor the survival and spread of droplet-mediated viral diseases. These viral transmissions found attenuated in warm and humid (high absolute humidity) environments. However, the role of temperature, humidity, and absolute humidity in the transmission of COVID-19 has not yet been well established. Therefore the study to investigate the meteorological condition for incidence and spread of COVID-19 infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease is required for India. In this work, we analyze the local weather patterns of the Indian region affected by the COVID-19 virus for March and April months, 2020. We have investigated the effect of meteorological parameters like Temperature, relative humidity, and absolute humidity on the rate of spread of COVID-19 using daily confirm cases in India. We have used daily averaged meteorological data for the last three years (2017-2019) for March and April month and the same for the year 2020 for March 1 to April 15. We found a positive association (Pearsons r=0.56) between temperature and daily COVID-19 cases over India. We found a negative association of humidity (RH and AH) with daily COVID-19 Cases (Persons r=-0.62, -0.37). We have also investigated the role of aerosol in spreading the pandemic across India because its possible airborne nature. For this, we have investigated the association of aerosols (AOD) and other pollutions (NO2) with COVID-19 cases during the study period and also during the first lockdown period (25 March-15 April) in India. We found a negative association in March when there were few cases, but in April, it shows positive association when the number of cases is more (for AOD it was r=-0.41 and r=0.28 respectively). During the lockdown period, aerosols (AOD) and other pollutants (NO2; an indicator of PM2.5) reduced sharply with a percentage drop of about 36 and 37, respectively. This reduction may have reduced the risk for COVID-19 through air transmission due to the unavailability of aerosol particles as a base. HYSPLIT forward trajectory model also shows that surface aerosols may travel up to 4 km according to wind and direction within three h of its generation. If coronavirus becomes airborne as suggested by many studies, then it may have a higher risk of transmission by aerosols particles. So relaxing in the lockdown and environmental rules in terms of pollutant emissions from power plants, factories, and other facilities would be a wrong choice and could result in more COVID-19 incidences and deaths in India. Therefore the current study, although limited, suggests that it is doubtful that the spread of COVID-19 would slow down in India due to meteorological factors, like high temperature and high humidity. Because a large number of cases have already been reported in the range of high Tem, high Relative, and high absolute humidity regions of India. Thus our results in no way suggest that COVID-19 would not spread in warm, humid regions or during summer/monsoon. So effective public health interventions should be implemented across India to slow down the transmission of COVID-19. If COVID-19 is indeed sensitive to environmental factors, it could be tested in the coming summer-monsoon for India. So the only summer is not going to help India until monsoon is coming. Only government mitigations strategies would be helpful, whether its lockdown, aggressive and strategic testing, medical facilities, imposing social distancing, encouraging to use face mask or monitoring by a mobile application (Aarogya Setu).

negative: Multiple viral etiologies in patients with influenza-like illness and severe acute respiratory infection in Qatar, 2013–2016 Presenter: Shazia Nadeem, Acting Head of Surveillance and Outbreak, Public Health Department, Ministry of Public Health, Doha, Qatar Background: Respiratory illnesses are a significant cause of morbidity and mortality. Qatar has a comprehensive surveillance system which includes influenza-like illness (ILI) and severe acute respiratory infection (SARI) and identification of the influenza and non-influenza viruses causing the infections. Purpose: The aim of this study was to determine the viruses causing acute respiratory illness in Qatar during 2013–2016. Methodology: Respiratory samples were collected from selected patients using WHO standard case definitions with ILI at the sentinel primary health care centre sites of the National Influenza Centre and patients with SARI admitted to sentinel hospitals. Nasopharyngeal and/or oropharyngeal swabs were collected from eligible patients (standardized case definitions) for the period 2013–2016. Samples were analysed by real-time polymerase chain reaction at the National Influenza Centre, which tests for 22 types and subtypes of virus. Findings: In the study period, 43 106 patients were included and tested, 29 626 (68.7%) of whom tested positive for infection. Out of these, 8 829 (29.8%) were influenza positive, 6 655 (75.4%) of whom were influenza A and 2 174 (24.6%) were influenza B. Sub-typing of influenza A showed 3 721 (55.9%) were influenza A(H1N1)pdm09. Other respiratory viruses isolated included rhinovirus 4 626 (15.6%), respiratory syncytial virus 3 259 (11.0%), coronaviruses 1 824 (6.2%), adenovirus 1 689 (5.7%), parainfluenza virus 1 645 (5.6%), human metapneumovirus 1 357 (4.6%) Mycoplasma pneumoniae 1 053 (3.6%), bocavirus 874 (3.0%) and parechovirus 178 (0.6%). Seasonal variation was observed for influenza with the peak season being from October to March with an unexpected surge of cases seen in October to December 2016. Conclusions: Influenza viruses A and B are responsible for the majority of the ILI and SARI cases reported in Qatar; however many other viruses also contribute to the burden of respiratory illness in the country. The findings indicate other viral etiologies besides influenza which may influence the clinical management and outcome of the patient. Keywords: Influenza; Influenza-like illness; Severe acute respiratory infection; Respiratory pathogens; Qatar

negative: Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: A global health emergency Abstract According to data compiled by researchers at Johns Hopkins University in Baltimore, Maryland, more than two and half million cases of coronavirus disease 2019 (COVID-19), caused by a newly discovered virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed on April 20, 2020 (Nature, 2020b). Since the emergence of this infectious disease in Asia (Wuhan, China) late last year, it has been subsequently span to every continent of the world except Antarctica (Rodríguez-Morales et al., 2020). Along with a foothold in every country, the current disease pandemic is disrupting practically every aspect of life all over the world. As the outbreak are continuing to evolve, several research activities have been conducted for better understanding the origin, functions, treatments, and preventions of this novel coronavirus. This review will be a summa of the key features of novel coronavirus (nCoV), the virus causing disease 2019 and the present epidemic situation worldwide up to April 20, 2020. It is expected that this record will play an important role to take more preventive measures for overcoming the challenges faced during this current pandemic.

negative: Influenza species and subtypes circulation among hospitalized patients in Laleh hospital during two influenza seasonal (2016-2017 and 2017-2018) using a multiplex Real Time-Polymerase Chain Reaction The introduction of polymerase chain reaction (PCR) techniques has improved the detection of respiratory viruses, particularly with the use of multiplex real-time technique with the capability of simultaneous detection of various pathogens in a single reaction. The aim of this study was to apply the above technology for the diagnosis of influenza infections and at the same time to differentiate between common flu species between hospitalized patients in Laleh hospital (Iran) between two flu seasons (2016-2017 and 2017-2018). Different respiratory specimens were collected from 540 patients from a period of December 2016 to May 2018 and were sent to the laboratory for molecular diagnosis. RNAs were extracted and subsequently, a multiplex real time PCR identifying flu A, flu B and typing flu A (H1N1) was carried out. The mean age of patients was 47.54±23.96. 216 (40%) and 321 (60%) of subjects were male and female, respectively. 219 out of 540 (40.5%) were positive for influenza infection including flu A (n=97, 44.3%), flu A (H1N1) (n=45, 20.7%) and flu B (n=77, 35%). Flu A was the dominant species on 2016-2017 and flu B was the major species on 2017-2018. Flu A (H1N1) was comparable in both time periods. Flu infections were most frequently diagnosed in age groups 21-40. Flu-positive patients suffered more from body pain and sore throat than flunegative patients with significant statistical difference (P values <0.001). The mean duration of hospitalization was shorter for flu-positive patients (P value = 0.016). Application of multiplex real time PCR could facilitate the influenza diagnosis in a short period of time, benefiting patients from exclusion of bacterial infections and avoiding unnecessary antibiotic therapy. Influenza diagnosis was not achieved in up to 60% of flu-like respiratory infections, suggesting the potential benefit of adopting the same methodology for assessing the involvement of other viral or/and bacterial pathogens in those patients.

negative: Using influenza surveillance networks to estimate state-specific prevalence of SARS-CoV-2 in the United States Detection of SARS-CoV-2 infections to date has relied heavily on RT-PCR testing. However, limited test availability, high false-negative rates, and the existence of asymptomatic or sub-clinical infections have resulted in an under-counting of the true prevalence of SARS-CoV-2. Here, we show how influenza-like illness (ILI) outpatient surveillance data can be used to estimate the prevalence of SARS-CoV-2. We found a surge of non-influenza ILI above the seasonal average in March 2020 and showed that this surge correlated with COVID-19 case counts across states. If 1/3 of patients infected with SARS-CoV-2 in the US sought care, this ILI surge would have corresponded to more than 8.7 million new SARS-CoV-2 infections across the US during the three-week period from March 8 to March 28, 2020. Combining excess ILI counts with the date of onset of community transmission in the US, we also show that the early epidemic in the US was unlikely to have been doubling slower than every 4 days. Together these results suggest a conceptual model for the COVID-19 epidemic in the US characterized by rapid spread across the US with over 80% infected patients remaining undetected. We emphasize the importance of testing these findings with seroprevalence data and discuss the broader potential to use syndromic surveillance for early detection and understanding of emerging infectious diseases.

negative: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Emergence, History, Basic and Clinical Aspects Abstract In late December 2019, the world woke to a reality of a pandemic of Coronavirus Disease (COVID-19), elicited by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which belongs to a group of β-coronavirus. The potential to cause life-threatening respiratory failure and rapid transmission puts COVID-19 in the list of Public Health Emergency of International Concern (PHEIC). In the last two decades, this is the 3rd deadliest Coronavirus pandemic, following SARS which lasted between 2002 and 2003 and Middle East Respiratory Syndrome (MERS) from 2012 till date. Globally and as of April 1st 2020, COVID-19 has affected 924,688 individuals in over 200 countries, causing 46,368 fatalities. While the SARS-CoV-2 originated in China with over 82,724 confirmed cases and more than 3000 deaths as at the time of writing this review, the rapid transmission of SARS-CoV-2 has resulted in exponential increase in the number of cases outside of China to about 10 times the report case and death in mainland China. SARS-CoV-2 is suspected to be zoonotic in nature as genetic studies have shown sequence similarity to viruses originating from bats. Extreme precautionary measures, such as curfew, shutting of borders and quarantining of individuals suspected to be infected have been instituted with immediate effect; however, due to individuals that are asymptomatic, uncontrolled human-to-human transmission has resulted in exponential infection rate and numerous loss of lives even with this lockdown measures. This review article summarizes the developing situation surrounding the SARS-CoV-2 pandemic with respect to its epidemiology, unique genomic structure, possible origins, transmission, pathogenesis, comparison with other deadly species of Coronaviruses (CoV) and emerging treatment strategies built on informed literature.

negative: Epidemiologic data and pathogen genome sequences: a powerful synergy for public health Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional ‘line lists’ (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.

negative: Comparative genomics of carp herpesviruses. Three alloherpesviruses are known to cause disease in cyprinid fish: cyprinid herpesviruses 1 and 3 (CyHV1 and CyHV3) in common carp and koi and cyprinid herpesvirus 2 (CyHV2) in goldfish. We have determined the genome sequences of CyHV1 and CyHV2 and compared them with the published CyHV3 sequence. The CyHV1 and CyHV2 genomes are 291,144 and 290,304 bp, respectively, in size, and thus the CyHV3 genome, at 295,146 bp, remains the largest recorded among the herpesviruses. Each of the three genomes consists of a unique region flanked at each terminus by a sizeable direct repeat. The CyHV1, CyHV2, and CyHV3 genomes are predicted to contain 137, 150, and 155 unique, functional protein-coding genes, respectively, of which six, four, and eight, respectively, are duplicated in the terminal repeat. The three viruses share 120 orthologous genes in a largely colinear arrangement, of which up to 55 are also conserved in the other member of the genus Cyprinivirus, anguillid herpesvirus 1. Twelve genes are conserved convincingly in all sequenced alloherpesviruses, and two others are conserved marginally. The reference CyHV3 strain has been reported to contain five fragmented genes that are presumably nonfunctional. The CyHV2 strain has two fragmented genes, and the CyHV1 strain has none. CyHV1, CyHV2, and CyHV3 have five, six, and five families of paralogous genes, respectively. One family unique to CyHV1 is related to cellular JUNB, which encodes a transcription factor involved in oncogenesis. To our knowledge, this is the first time that JUNB-related sequences have been reported in a herpesvirus.

negative: Public health: Life lessons The 2009 pandemic arrived suddenly and lethally, exposing our plans to reality. Are we now better prepared?

negative: 2009 H1N1 Influenza: A Twenty-First Century Pandemic With Roots in the Early Twentieth Century Abstract A swine-origin H1N1 triple-reassortant influenza A virus found to be a distant relative of the 1918 “Spanish flu” virus emerged in April 2009 to give rise to the first influenza pandemic of the 21st century. Although disease was generally mild and similar to seasonal influenza, severe manifestations including respiratory failure were noted in some, particularly those with underlying conditions such as asthma, pregnancy and immunosuppression. Children and younger adults accounted for most cases, hospitalizations and deaths. A reverse transcriptase-polymerase chain reaction assay was superior to antigen-based rapid tests for diagnosis. All 2009 H1N1 pandemic influenza strains were susceptible to 1 or more neuraminidase inhibitors. Monovalent, unadjuvanted 2009 H1N1 vaccines were licensed in the United States in September 2009 and initially targeted to younger individuals, pregnant women, caretakers of infants and healthcare providers. The 2009 H1N1 pandemic highlights the need for modernization of influenza vaccines, improved diagnostics and more rigorous evaluation of mitigation strategies.

negative: Reverse Genetics Approaches for the Development of Influenza Vaccines Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines.

negative: Mitigation Approaches to Combat the Flu Pandemic Management of flu pandemic is a perpetual challenge for the medical fraternity since time immemorial. Animal to human transmission has been observed thrice in the last century within an average range of 11-39 years of antigenic recycling. The recent outbreak of influenza A (H1N1, also termed as swine flu), first reported in Mexico on April 26, 2009, occurred in the forty first year since last reported flu pandemic (July 1968). Within less than 50 days, it has assumed pandemic proportions (phase VI) affecting over 76 countries with 163 deaths/35,928 cases (as on 15(th) June 2009). It indicated the re-emergence of genetically reassorted virus having strains endemic to humans, swine and avian (H5N1). The World Health Organisation (WHO) member states have already pulled up their socks and geared up to combat such criticalities. Earlier outbreaks of avian flu (H5N1) in different countries led WHO to develop pandemic preparedness strategies with national/regional plans on pandemic preparedness. Numerous factors related to climatic conditions, socio-economic strata, governance and sharing of information/logistics at all levels have been considered critical indicators in monitoring the dynamics of escalation towards a pandemic situation. The National Disaster Management Authority (NDMA), Government of India, with the active cooperation of UN agencies and other stakeholders/experts has formulated a concept paper on role of nonhealth service providers during pandemics in April 2008 and released national guidelines - management of biological disasters in July 2008. These guidelines enumerate that the success of medical management endeavors like pharmaceutical (anti-viral Oseltamivir and Zanamivir therapies), nonpharmaceutical interventions and vaccination development etc., largely depends on level of resistance offered by mutagenic viral strain and rationale use of pharmaco therapeutic interventions. This article describes the mitigation approach to combat flu pandemic with its effective implementation at national, state and local levels.

negative: Pandemic Influenza: Impact on Perianesthesia Nursing Areas As our readers are aware, these pages are typically used by the editors. However, in light of the recent events and concerns surrounding the swine flu, the editors have elected to quickly substitute an informative piece regarding influenza for the usual editorial. We thank Dr. Daphne Stannard for her willingness to disseminate her knowledge on the topic. The Editors

negative: Public Health Aspects of COVID-19 Infection with Focus on Cardiovascular Diseases INTRODUCTION: COVID-19 is the disease caused by an infection of the SARS-CoV-2 virus, first identified in the city of Wuhan, in China’s Hubei province in December 2019. COVID-19 was previously known as 2019 Novel Coronavirus (2019-nCoV) respiratory disease before the World Health Organization (WHO) declared the official name as COVID-19 in February 2020. AIM: The aim of this study is to search scientific literature in the biomedicine and analyzed current results of investigations regarding morbidity and mortality rates as consequences of COVID-19 infection of Cardiovascular diseases (CVD), and other most common chronic diseases which are on the top mortality and morbidity rates in almost all countries in the world. Also, to propose most useful measures how to prevent patients to keep themselves against COVID-19 infection. METHODS: We used method of descriptive analysis of the published papers with described studies about Corona virus connected with CVD, and, also, Guidelines proposed by World Health Organization (WHO) and European Society of Cardiology (ESC), and some other international associations which are included in global fighting against COVID-19 infection. RESULTS: After searching current scientific literature we have acknowledged that not any Evidence Based Medicine (EBM) study in the world during last 5 months from the time when first cases of COVID-10 infection was detected. Also, there is no unique proposed ways of treatments and drugs to protect patients, especially people over 65 years old, who are very risk group to be affected with COVID-19. Expectations that vaccine against COVID-19 will be produced optimal during at least 10 months to 2 years, and in all current Guidelines most important proposed preventive measures are the same like which one described in Strategic documents of WHO, in statements of Declaration of Primary Health Care in Alma Ata in 1978. CONCLUSION: WHO proposed preventive measures can be helpful to everybody. Physicians who work at every level of Health Care Systems, but especially at primary health care level, must follow those recommendations and teach their patients about it. But, the fact is that current focus of COVID-19 epidemic has targeted on protection of physical health of population in global, however, the influence on mental health which will be one of the important consequences of COVID-19 pandemic in the future, and which could be declared as «Post-coronavirus Stress Syndrome„ (PCSS) could be bigger challenge for Global Public Health.

negative: Surveillance of community-acquired viral infections due to respiratory viruses in Rhone-Alpes (France) during winter 1994 to 1995. Nasal swab from patients with acute flu-like illness were evaluated for the presence of respiratory viruses in the Rhone-Alpes region of France from 1 October 1994 through 2 May 1995. The relative frequencies and seasonal distributions of the specific viruses were assessed. In addition, virus type was correlated with specific clinical signs and symptoms. During the study, 962 samples were collected by 75 medical practitioners participating in the Groupe Regional d'Observation de la Grippe surveillance network. One or more viruses were detected from 348 samples (36.1%), including 108 respiratory syncytial virus (RSV), 64 influenza virus A type H3N2, 47 influenza virus B, 64 coronavirus, 35 rhinovirus, 22 adenovirus, 5 enterovirus, and 3 parainfluenza-fluenza strains. There were 16 mixed infections. RSV infections peaked in the early winter, and influenza viruses A and B infections peaked during the late winter and early spring. There were two peaks of coronavirus infections (late fall and late winter). Other viruses were detected at lower levels throughout the study period. Patients from whom adenovirus was isolated were significantly more likely to have a fever of > 39.5 degrees C than were patients with other detectable viruses (P < 0.001). Furthermore, there was a significant correlation between influenza and cough (P < 0.01) and RSV and bronchiolitis (P < .001). Thus, the current study defined the overall and relative frequencies of respiratory virus detection from nasal swab specimens in patients with an acute flu-like illness in the Rhone-Alpes region of France during a 7-month period. Correlation with clinical signs and symptoms and provisional conclusions regarding seasonality were also determined.

negative: Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters OBJECTIVE: To evaluate the relative risk of COVID-19 death in people <65 years old versus older individuals in the general population, to provide estimates of absolute risk of COVID-19 death at the population level, and to understand what proportion of COVID-19 deaths occur in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Countries and US states or major cities with at least 250 COVID-19 deaths as of 4/4/2020 and with information available on death counts according to age strata, allowing to calculate the number of deaths in people with age <65. Data were available for Belgium, Germany, Italy, Netherlands, Portugal, Spain, Sweden, and Switzerland, as well as Louisiana, Michigan, Washington states and New York City as of April 4, 2020. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths that occur in people <65 years old; relative risk of COVID-19 death in people <65 versus ≥65 years old; absolute risk of death in people <65 and in those ≥80 years old in the general population as of 4/4/2020; absolute death risk expressed as equivalent of death risk from driving a motor vehicle. RESULTS: Individuals with age <65 account for 5%-9% of all COVID-19 deaths in the 8 European epicenters, and approach 30% in three US hotbed locations. People <65 years old had 34- to 73-fold lower risk than those ≥65 years old in the European countries and 13- to 15-fold lower risk in New York City, Louisiana and Michigan. The absolute risk of COVID-19 death ranged from 1.7 per million for people <65 years old in Germany to 79 per million in New York City. The absolute risk of COVID-19 death for people ≥80 years old ranged from approximately 1 in 6,000 in Germany to 1 in 420 in Spain. The COVID-19 death risk in people <65 years old during the period of fatalities from the epidemic was equivalent to the death risk from driving between 9 miles per day (Germany) and 415 miles per day (New York City). People <65 years old and not having any underlying predisposing conditions accounted for only 0.3%, 0.7%, and 1.8% of all COVID-19 deaths in Netherlands, Italy, and New York City. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in the hotbeds of the pandemic and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.

negative: Performance of urea-mediated dissociation in reducing false-positive of 2019-nCoV IgM test/ 中华检验医学杂志 Objective@#To investigate the interference factors causing false-positive result of novel coronavirus IgM antibody (SARS-CoV-2 IgM) detected by gold immunochromatography assay (GICA) and enzyme-linked immunosorbent assay (ELISA).@*Methods@#A total of 71 serum from different pathogen infections and related chronic diseases patients were collected from the Affiliated Hospital of North Sichuan Medical College from January 25, 2020 to February 15, 2020. GICA and ELISA were used to detect 2019-nCoV IgM in 71 serum, including 5 influenza A virus (Flu A) IgM positive serum, 5 influenza B virus (Flu B) IgM positive serum, 5 Mycoplasma pneumonia (MP) IgM positive serum, 5 Legionella pneumophila (LP) IgM positive serum, 29 rheumatoid factor (RF) IgM positive serum, 5 hypertension patients serum, 5 diabetes mellitus patients serum, 6 human immunodeficiency virus (HIV) infection patients serum and 6 Corona Virus Disease 2019 (COVID-19) patients serum. The interference factors causing false positive results of the two methods were analyzed, and urea dissociation test was employed to dissociate the 2019-nCoV IgM positive serum using the best dissociation concentration. Statistical analyses were performed by SPSS, version 19.0.@*Result@#s 2019-nCoV IgM was positive in 18 cases of middle-high level RF-IgM positive serum and 6 cases of 2019-nCoV-infected serum detected by two methods, and the other 47 serum were negative. When the dissociation concentration of urea was 6 mol/L, 2019-nCoV IgM was negative in 17 cases of middle-high level RF-IgM positive serum and positive in 6 cases of 2019-nCoV-infected serum detected by GICA. When the urea dissociation concentration was 4 mol/L, dissociation time was 10 min and the avidity index<0.46 was set as negative, 2019-nCoV IgM was negative in 15 cases of middle-high level RF-IgM positive serum and positive in 6 cases of 2019-nCoV-infected serum detected by ELISA.@*Conclusion@#The middle-high level of RF-IgM could cause false positive results of SARS-CoV-2 IgM detected by GICA and ELISA, and the urea dissociation test would be helpful for reducing the probability of false-positive results of SARS-CoV-2 IgM test.

negative: First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM). METHODS: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (C(t)) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory confirmed COVID-19 infections. Two SARS-CoV-2 positive cases remained clinically asymptomatic. Eleven cases reported flu-like symptoms without positive results. C(t) values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (p =0.007). CONCLUSION: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at the UHM. Semi quantitative real-time RT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2 infected HCWs in order to prevent COVID-19 outbreaks in the hospital setting.

negative: Ten year retrospective evaluation of the seasonal distribution of agent viruses in childhood respiratory tract infections. AIM Infections caused by respiratory viruses sometimes occur as epidemias or pandemias and are an important public health problem in the whole world. These viral agents may lead to severe respiratory diseases especially in young children and in the elderly. The aim of this study was to determine the seasonal distribution of agent viruses in childhood respiratory infections in our region. MATERIAL AND METHODS In this study, nasopharyngeal swab sample was obtained from 1 326 patients who presented to Ege University, Medical Faculty Children's Hospital between 2002 and 2012 and who were thought to have respiratory tract infection. Influenza virus type A and B, respiratory syncytial virus, adenovirus and parainfluenza virus type 1-3 were investigated using shell-vial cell culture method and direct fluorescent antibody test and/or multiplex PCR test. Parainfluenza virus type 4, human metapneumovirus, rhinovirus, coronavirus, human bocavirus were investigated using multiplex PCR test. The seasonal distributions of the viruses were determined according to the results obtained from Ege University Medical Faculty, Department of Medical Microbiology Clinical Virology Laboratory. Approval was obtained from the ethics committee (Ege University Clinical Researches Ethics Committee, 12.02.2013, number: 13-1/46). RESULTS The majority of the patients who presented were outpatients (n:888, 67%) and the remainder were hospitalized patients (33%, n:438). Respiratory viruses were found in 503 of the nasopharyngeal swab samples (38%). Parainfluenza and respiratory syncytial virus were found most frequently in December-february (58% and 59%, respectively, influenza viruses were found most frequently in November-december (72%) and adenoviruses were found most frequently in may-september (56%). CONCLUSION Although only supportive therapies are administered generally in viral infections, viral investigations are important in terms of determining the measures to be taken by determining the causes as well as in terms of establishing a general database. Another benefit of this study would be strengthening clinical approach to patients and decreasing unnecessary antibiotic use.

negative: The outbreak of Coronavirus Disease 2019 (COVID-19)—An emerging global health threat Abstract The outbreak of Coronavirus Disease 2019 (COVID-19) causing novel coronavirus-infected pneumonia (NCIP), has affected the lives of 71,429 people globally. Originating in China, the disease has a rapid progression to other countries. Research suggests remarkable genomic resemblance of 2019-nCoV with Severe Acute Respiratory Syndrome (SARS) which has a history of a pandemic in 2002. With evidence of nosocomial spread, a number of diligent measures are being employed to constrain its propagation. Hence, the Public Health Emergency of International Concern (PHEIC) has been established by the World Health Organization (WHO) with strategic objectives for public health to curtail its impact on global health and economy.

negative: Coronavirus Perceptions And Economic Anxiety We provide one of the first systematic assessments of the development and determinants of economic anxiety at the onset of the coronavirus pandemic. Using a global dataset on internet searches and two representative surveys from the US, we document a substantial increase in economic anxiety during and after the arrival of the coronavirus. We also document a large dispersion in beliefs about the pandemic risk factors of the coronavirus, and demonstrate that these beliefs causally affect individuals' economic anxieties. Finally, we show that individuals' mental models of infectious disease spread understate non-linear growth and shape the extent of economic anxiety.

negative: Data for understanding the risk perception of COVID-19 from Vietnamese sample This data article describes the risk perception of COVID-190 from 391 Vietnamese respondents aged from 15 to 47 years. These data have been used in Huynh (2020). These data include the socioeconomics, media attention, and risk perception of COVID-19 in Vietnam through a survey conducted on February 1, 2020. In addition, our data might serve as a reference source for further in-depth surveys to understand the risk perception and social media communication across countries.

negative: Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation Summary Background Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe lower respiratory tract infection in people. Previous studies suggested dromedary camels were a reservoir for this virus. We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. Methods We took nose swabs, rectal swabs, and blood samples from all camels on the Qatari farm. We tested swabs with RT-PCR, with amplification targeting the E gene (upE), nucleocapsid (N) gene, and open reading frame (ORF) 1a. PCR positive samples were tested by different MERS-CoV specific PCRs and obtained sequences were used for phylogentic analysis together with sequences from the linked human cases and other human cases. We tested serum samples from the camels for IgG immunofluorescence assay, protein microarray, and virus neutralisation assay. Findings We obtained samples from 14 camels on Oct 17, 2013. We detected MERS-CoV in nose swabs from three camels by three independent RT-PCRs and sequencing. The nucleotide sequence of an ORF1a fragment (940 nucleotides) and a 4·2 kb concatenated fragment were very similar to the MERS-CoV from two human cases on the same farm and a MERS-CoV isolate from Hafr-Al-Batin. Eight additional camel nose swabs were positive on one or more RT-PCRs, but could not be confirmed by sequencing. All camels had MERS-CoV spike-binding antibodies that correlated well with the presence of neutralising antibodies to MERS-CoV. Interpretation Our study provides virological confirmation of MERS-CoV in camels and suggests a recent outbreak affecting both human beings and camels. We cannot conclude whether the people on the farm were infected by the camels or vice versa, or if a third source was responsible. Funding European Union projects EMPERIE (contract number 223498), ANTIGONE (contract number 278976), and the VIRGO consortium.

negative: Predicting the anticipated emotional and behavioral responses to an avian flu outbreak BACKGROUND: The purpose of this study was to develop a model to predict the emotional and behavioral responses to an avian flu outbreak. METHODS: The participants were 289 university students ranging in age, income, and ethnic backgrounds. They were presented with scenarios describing avian flu outbreaks affecting their community. They reported their anticipated emotional responses (positive emotion, negative emotion) and behavioral responses (helping, avoidance, sacrifice, illegal behavior) as if the scenarios were actually occurring. They also were assessed on individual differences expected to predict their responses. RESULTS: Participants were only modestly familiar with the avian flu and anticipated strong emotional and behavioral responses to an outbreak. Path analyses were conducted to test a model for predicting responses. The model showed that age, sex, income, spirituality, resilience, and neuroticism were related to responses. Spirituality, resilience, and income predicted better emotional responses, and neuroticism and female sex predicted worse emotional responses. Age, sex, income, and spirituality had direct effects on behavior. The emotional responses were directly related to each behavior and mediated the effects of individual differences. CONCLUSION: Emotional responses may be important in predicting behavior after an outbreak of avian flu, and personal characteristics may predict both emotional and behavioral responses.

negative: Mathematical modeling of interaction between innate and adaptive immune responses in COVID‐19 and implications for viral pathogenesis We have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease‐2019 (COVID‐19) pandemic caused by SARS‐CoV‐2 virus. We first validated our model using the well‐studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID‐19 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. The adaptive immune response of the COVID‐19 patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID‐19 patients while enhancing viral clearance in influenza patients. Stronger adaptive immunity in COVID‐19 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high‐risk COVID‐19 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.

negative: Recent advances in “universal” influenza virus antibodies: the rise of a hidden trimeric interface in hemagglutinin globular head Influenza causes seasonal outbreaks yearly and unpredictable pandemics with high morbidity and mortality rates. Despite significant efforts to address influenza, it remains a major threat to human public health. This issue is partially due to the lack of antiviral drugs with potent antiviral activity and broad reactivity against all influenza virus strains and the rapid emergence of drug-resistant variants. Moreover, designing a universal influenza vaccine that is sufficiently immunogenic to induce universal antibodies is difficult. Some novel epitopes hidden in the hemagglutinin (HA) trimeric interface have been discovered recently, and a number of antibodies targeting these epitopes have been found to be capable of neutralizing a broad range of influenza isolates. These findings may have important implications for the development of universal influenza vaccines and antiviral drugs. In this review, we focused on the antibodies targeting these newly discovered epitopes in the HA domain of the influenza virus to promote the development of universal anti-influenza antibodies or vaccines and extend the discovery to other viruses with similar conformational changes in envelope proteins.

negative: Analysis of heart injury laboratory parameters in 273 COVID‐19 patients in one hospital in Wuhan, China An outbreak of severe acute respiratory syndrome novel coronavirus (SARS‐CoV‐2) epidemic spreads rapidly worldwide. SARS‐CoV‐2 infection caused mildly to seriously and fatally respiratory, enteric, cardiovascular, and neurological diseases. In this study, we detected and analyzed the main laboratory indicators related to heart injury, creatine kinase isoenzyme‐MB (CK‐MB), myohemoglobin (MYO), cardiac troponin I (ultra‐TnI), and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), in 273 patients with COVID‐19 and investigated the correlation between heart injury and severity of the disease. It was found that higher concentration in venous blood of CK‐MB, MYO, ultra‐TnI, and NT‐proBNP were associated with the severity and case fatality rate of COVID‐19. Careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with COVID‐19.

negative: Epidemiological study of influenza virus infections in young adult outpatients from Buenos Aires, Argentina Background Influenza virus is the most common cause of influenza‐like illness (ILI) in adults. In Argentina, studies on influenza and other respiratory viruses were performed mostly in pediatric populations. Objectives To determine: (1) the frequency of influenza virus and other common respiratory viruses in adult outpatients with ILI, (2) whether the signs and symptoms predict viral etiology, (3) whether viral diagnosis changes clinical management or infection control measures and (4) to characterize the influenza strains circulating in the community. Population and methods Nasal and pharyngeal swabs from adult outpatients with ILI attending the emergency room during the winter seasons of 2004 and 2005 in Argentina were evaluated by immunofluorescence and RT‐PCR. Results Of 151 samples analyzed, 39 (26%) were influenza A positive, 5 (3·3%) influenza B positive and 4 (2·6%) respiratory syncytial virus positive by immunofluorescence. Two samples (1·3%) were human metapneumovirus positive by RT PCR. Cell culture detected six additional influenza viruses and one adenovirus positive sample. The sensitivity of immunofluorescence for influenza compared with culture was 70%. Symptoms did not predict etiology. Conclusions In this study, 40% of the patients with ILI had a specific viral infection and 83% were influenza viruses. Viral detection was necessary to determine the etiology as signs and symptoms were not different between patients with or without viral infection. Viral diagnosis was important to implement infectious control measures. Circulating influenza strains in this study were similar to the correspondent vaccine strains selected for the Southern hemisphere.

negative: Swine and Avian Influenza Outbreaks in Recent Times Influenza A is a zoonotic virus and wild waterfowls are the main reservoir of avian influenza viruses, which are precursors of human influenza A viruses. Through mutations and gene reassortment, some strains of avian influenza viruses establish stable lineages in poultry species, pigs, horses, and humans. The first zoonotic influenza pandemic of the twenty-first century, the swine H1N1 pandemic of 2009, originated from Mexico, and fortunately the virus was only of modest virulence. However, lessons have been learned on the shortcomings of the global preparedness for influenza pandemic, and this should be considered as a valuable experience for the preparation of the next major outbreak. Of more concern is the emergence of the highly pathogenic avian influenza A [H5N1], ongoing since 1996, and the low pathogenic avian influenza A [H7N9], since 2013, which have crossed the species barrier to humans in China. Risks of a H5N1 pandemic appear to be receding with declining human cases, and the H7N9 influenza virus is now the leading candidate as the next pandemic influenza virus. However, influenza pandemics are unpredictable in their timing, specific strain of virus, and origin. Most experts predict that the next influenza pandemic will arise from Asia, especially China, and will be directly of avian origin. Continued influenza surveillance in animals and humans globally with prompt reporting to the WHO and the World Animal Health Organization with sharing of data promptly between countries is essential. Long-term solutions to prevent cross-species transmission of zoonotic influenza viruses to humans and development of more effective, longer-lasting vaccines against emerging avian influenza viruses are needed. Currently there is no evidence of an impending zoonotic or avian influenza pandemic, and the viruses of interest, H5N1 and H7N9 avian influenza A viruses, have not mutated to allow for easy transmission to humans nor human to human.

negative: The impact of influenza and respiratory syncytial virus on hospitalizations for lower respiratory tract infections in young children: Slovenia, 2006–2011 BACKGROUND: Influenza and respiratory syncytial viruses (RSV) are important viral pathogens in childhood. OBJECTIVES: Our aim was to estimate the effect of influenza and RSV on excess hospitalizations for acute lower respiratory tract infections (ALRTI) in children aged ≤5. METHODS: Retrospective, population‐based study was performed for five seasons (2006–2011). Slovenian national hospital discharge data and surveillance data were used to estimate the effect of influenza and/or RSV on ALRTI hospitalizations (acute bronchiolitis, pneumonia, and acute bronchitis) using rate difference method. RESULTS: An excess was observed in average weekly ALRTI hospitalizations per 100 000 among children aged ≤5 in all five seasons during influenza and/or RSV active period. During three seasons, there was higher excess in ALRTI hospitalizations in the period when influenza/RSV cocirculated compared with the RSV period. In pandemic season (2009/2010), the only one without influenza/RSV overlap, excess hospitalization was higher in RSV period. The highest excess of hospitalizations was found among the youngest children (0‐5 months old). In all five seasons, acute bronchiolitis was the most common ALRTI recorded in hospitalized young children. CONCLUSIONS: Respiratory syncytial viruses was leading viral pathogen associated with ALRTI hospitalizations in children aged ≤5. The cocirculation of influenza virus increased the burden of ALRTI hospitalizations especially in seasons with A(H3) predominance.

negative: Structural Analogs of Umifenovir. 1. Synthesis and Biological Activity of Ethyl 5-Hydroxy-1-Methyl-2-(Trans-2-Phenylcyclopropyl)-1H-Indole-3-Carboxylate Ethyl 5-hydroxy-1-methyl-2-(trans-2-phenylcyclopropyl)-1H-indole-3-carboxylate is the first prototype of conformationally restricted analogs of umifenovir. It has been prepared using a one-pot method and has undergone an antiviral study.

negative: Sex differences in clinical findings among patients with coronavirus disease 2019 (COVID-19) and severe condition Objective: To compare the sex differences in the clinical findings among patients with severe coronavirus disease 2019 (COVID-19). Methods: We retrospectively collected data of 47 patients diagnosed as severe type of COVID-19 from February 8 to 22, 2020, including demographics, illness history, physical examination, laboratory test, management, and compared differences between men and women. Results: Of the 47 patients, 28 (59.6%) were men. The median age was 62 years, and 30 (63.8%) had comorbidities. The initial symptoms were mainly fever (34 [72.3%]), cough (36 [76.6%]), myalgia (5 [10.6%]) and fatigue (7 [14.9%]). Procalcitonin level was higher in men than in women (0.08 vs. 0.04ng/ml, p=0.002). N-terminal-pro brain natriuretic peptide increased in 16 (57.1%) men and 5 (26.3%) women (p=0.037). Five men (17.9%) had detected positive influenza A antibody, but no women. During 2-week admission, 5 (17.9%) men and 1 (5.3%) woman were reclassified into the critical type due to deterioration. Mortality was 3.6% in men and 0 in women respectively. Four (21.1%) women and one man (3.6%) recovered and discharged from hospital. Conclusion: Sex differences may exist in COVID-19 patients of severe type. Men are likely to have more complicated clinical condition and worse in-hospital outcomes as compared to women.

negative: Automatic Detection of Coronavirus Disease (COVID-19) Using X-ray Images and Deep Convolutional Neural Networks The 2019 novel coronavirus (COVID-19), with a starting point in China, has spread rapidly among people living in other countries, and is approaching approximately 12,245,417 cases worldwide according to the statistics of European Centre for Disease Prevention and Control. There are a limited number of COVID-19 test kits available in hospitals due to the increasing cases daily. Therefore, it is necessary to implement an automatic detection system as a quick alternative diagnosis option to prevent COVID-19 spreading among people. In this study, three different convolutional neural network based models (ResNet50, InceptionV3 and Inception-ResNetV2) have been proposed for the detection of coronavirus pneumonia infected patient using chest X-ray radiographs. ROC analyses and confusion matrices by these three models are given and analyzed using 5-fold cross validation. Considering the performance results obtained, it is seen that the pre-trained ResNet50 model provides the highest classification performance with 98% accuracy among other two proposed models (97% accuracy for InceptionV3 and 87% accuracy for Inception-ResNetV2).

negative: Influenza vaccination and respiratory virus interference among Department of Defense personnel during the 2017–2018 influenza season PURPOSE: Receiving influenza vaccination may increase the risk of other respiratory viruses, a phenomenon known as virus interference. Test-negative study designs are often utilized to calculate influenza vaccine effectiveness. The virus interference phenomenon goes against the basic assumption of the test-negative vaccine effectiveness study that vaccination does not change the risk of infection with other respiratory illness, thus potentially biasing vaccine effectiveness results in the positive direction. This study aimed to investigate virus interference by comparing respiratory virus status among Department of Defense personnel based on their influenza vaccination status. Furthermore, individual respiratory viruses and their association with influenza vaccination were examined. RESULTS: We compared vaccination status of 2880 people with non-influenza respiratory viruses to 3240 people with pan-negative results. Comparing vaccinated to non-vaccinated patients, the adjusted odds ratio for non-flu viruses was 0.97 (95% confidence interval (CI): 0.86, 1.09; p = 0.60). Additionally, the vaccination status of 3349 cases of influenza were compared to three different control groups: all controls (N = 6120), non-influenza positive controls (N = 2880), and pan-negative controls (N = 3240). The adjusted ORs for the comparisons among the three control groups did not vary much (range: 0.46–0.51). CONCLUSIONS: Receipt of influenza vaccination was not associated with virus interference among our population. Examining virus interference by specific respiratory viruses showed mixed results. Vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus; however, significant protection with vaccination was associated not only with most influenza viruses, but also parainfluenza, RSV, and non-influenza virus coinfections.

negative: Lower respiratory tract infection in the community: associations between viral aetiology and illness course Abstract Objectives This study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection (LRTI). Methods A prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between Nov-Apr 2007-2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1=no problem, 2=mild, 3=moderate, 4=severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed. Results The PCR tested positive for a common respiratory virus in 1,354 of the 2,957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95%CI 2.07-2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50-11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07-0.25 points or 2.3-8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95%CI 0.65-0.96) and hMPV infections (AHR 0.77, 95%CI 0.62-0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95%CI 0.06-0.16 per 10 cycles decrease in Ct value), but not with symptom duration. Conclusions In healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected LRTI respiratory viruses other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened.

negative: Alignment-Free Analyses of Nucleic Acid Sequences Using Graphical Representation (with Special Reference to Pandemic Bird Flu and Swine Flu) The exponential growth in database of bio-molecular sequences have spawned many approaches towards storage, retrieval, classification and analyses requirements. Alignment-free techniques such as graphical representations and numerical characterisation (GRANCH) methods have enabled some detailed analyses of large sequences and found a number of different applications in the eukaryotic and prokaryotic domain. In particular, recalling the history of pandemic influenza in brief, we have followed the progress of viral infections such as bird flu of 1997 onwards and determined that the virus can spread conserved over space and time, that influenza virus can undergo fairly conspicuous recombination-like events in segmented genes, that certain segments of the neuraminidase and hemagglutinin surface proteins remain conserved and can be targeted for peptide vaccines. We recount in some detail a few of the representative GRANCH techniques to provide a glimpse of how these methods are used in formulating quantitative sequence descriptors to analyse DNA, RNA and protein sequences to derive meaningful results. Finally, we survey the surveillance techniques with a special reference to how the GRANCH techniques can be used for the purpose and recount the forecasts made of possible metamorphosis of pandemic bird flu to pandemic human infecting agents.

negative: Factors in vaccination intention against the pandemic influenza A/H1N1 Background: Vaccination against pandemic influenza A/H1N1 is an effective strategy to mitigate the spread of the disease. While the vaccine is now available, social acceptance remains relatively uncertain in many societies. The purpose of this study was to examine the beliefs, attitudes and practices associated with the intention to get vaccinated against the A/H1N1 virus among the general population in France. Methods: A representative sample of 1001 individuals (stratified random recruitment procedure, ages 16–90 years) was interviewed by telephone. The questionnaire included a variety of items associated with socio-demographic characteristics, risk perceptions, illness perceptions, political attitudes and worldviews as well as intention to get vaccinated. Results: More than 6 out of 10 of the respondents indicated that they planned to get vaccinated when the vaccine becomes available. The same proportion of parents also reported the intention to vaccinate their children against the disease. In multiple regression analyses, socio-cognitive factors consistently predicting influenza A/H1N1 vaccination were: level of worry, risk perception and previous experience of vaccine against seasonal flu. Conclusions: The factors found to predict vaccination intention and their distribution are assumed to be a consequence of the fact that people perceive the risk of swine flu to be similar to that of seasonal flu. As a result, in the absence of an increase of the risk perception of pandemic influenza A/H1N1, a very low level of actual vaccination is forecasted. Behavioural change would require that the risks and consequences of pandemic influenza A/H1N1 be perceived as highly different from seasonal flu.

negative: Differential Diagnosis of Common Acute Toxicologic Versus Nontoxicologic Illness This table outlines common toxicologic versus nontoxicologic rule outs based on clinical abnormalities seen in an acutely ill animal. The purpose is to provide an initial guideline for considering toxicologic versus nontoxicologic rule outs when a patient is presented to a practicing veterinarian. Major clinical abnormalities followed by common toxicologic rule outs and non-toxicologic rule outs have been listed so that practicing veterinarians can narrow down an etiology quickly. Based on history, physical examination findings, and blood work changes, once a reasonable etiology has been narrowed down or established, the reader is encouraged to review a more detailed discussion on management of the particular poisoning or disease listed in this or other references.

negative: SARS - CoV-2: Reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis) The novel coronavirus Covid-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against Covid-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics ("Spanish flu" 1918, "Asian flu" 1956 and "the Hong Kong flu" 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4 + memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4 + memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting "lung crash" until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the Covid-19 will occur.

negative: Containing 2019-nCoV (Wuhan) coronavirus The novel coronavirus 2019-nCoV first appeared in December 2019 in Wuhan, China. While most of the initial cases were linked to the Huanan Seafood Wholesale Market, person-to-person transmission has been verified. Given that a vaccine cannot be developed and deployed for at least a year, preventing further transmission relies upon standard principles of containment, two of which are the isolation of known cases and the quarantine of persons believed at high risk of exposure. This note presents probability models for assessing the effectiveness of case isolation and quarantine within a community during the initial phase of an outbreak with illustrations based on early observations from Wuhan.

negative: Clinical features of children hospitalized with influenza A and B infections during the 2012–2013 influenza season in Italy BACKGROUND: Influenza is a major public health issue worldwide. It is characterized by episodes of infection that involve hundreds of millions of people each year. Since that in the seasons 2010–2011 and 2011–2012 the circulation of FLUB was decreasing we evaluated the clinical presentation, demographic characteristics, admitting department, and length of stay in children who contracted influenza admitted to Bambino Gesù Children’s Hospital, during the 2012–2013 influenza season, with the aim to establish if the recover of FLUB was associated to a clinical worsening, in comparison with those due to FLUA. METHODS: A total of 133 respiratory specimens, collected from patients with symptoms of respiratory tract infections, positive for the Influenza A and B viruses (FLUA and B) were subtyped. Comparisons between the FLUA and FLUB groups were performed with the one-way ANOVA for continuous parametric variables, the Mann-Whitney test for non-parametric variables, or the Chi-Square test or Fisher’s exact test (if cells <5) for categorical variables. RESULTS: 87.09 % of the FLUA isolates were the H1N1 subtype and 12.90 % were H3N2. Among the FLUB isolates, 91.54 % were the B/Yamagata/16/88 lineage and 8.45 % were the B/Victoria/02/87 lineage. The largest number of FLUA/H1N1 cases was observed in children less than 1 years old, while the B/Yamagata/16/88 lineage was most prevalent in children 3–6 years old. Fever was a common symptom for both FLUA and B affected patients. However, respiratory symptoms were more prevalent in patients affected by FLUA. The median length of stay in the hospital was 5 days for FLUA and 3 days for FLUB. CONCLUSIONS: The clinical features correlated to different Influenza viruses, and relevant subtypes, were evaluated concluding that the increasing of FLUB in the season 2012–2013 was without any dramatic change in clinical manifestation. Our findings suggest, finally, that a stronger commitment to managing patients affected by FLUA is required, as the disease is more severe than FLUB.

negative: Introduction: A Prelude to Mathematical Epidemiology Recorded history continuously documents the invasion of populations by infectious agents, some causing many deaths before disappearing, others reappearing in invasions some years later in populations that have acquired some degree of immunity, due to prior exposure to related infectious pathogens. The “Spanish” flu epidemic of 1918–1919 exemplifies the devastating impact of relatively rare pandemics; this one was responsible for about 50,000,000 deaths worldwide, while on the mild side of the spectrum we experience annual influenza seasonal epidemics that cause roughly 35,000 deaths in the USA each year.

negative: Predicting the epidemic curve of the coronavirus (SARS-CoV-2) disease (COVID-19) using artificial intelligence Objectives: The current form of severe acute respiratory syndrome called coronavirus disease 2019 (COVID19) caused by a coronavirus (SARSCoV2) is a major global health problem. The aim of our study was to use the official data and predict the possible outcomes of the COVID 19 pandemic using artificial intelligence (AI) based RNNs (Recurrent Neural Networks), then compare and validate the predicted and observed data. Materials and Methods: We used the publicly available datasets of World Health Organization and Johns Hopkins University to create the training dataset, then have used recurrent neural networks (RNNs) with gated recurring units (Long Short Term Memory: LSTM units) to create 2 Prediction Models. Information collected in the first t time steps were aggregated with a fully connected (dense) neural network layer and a consequent regression output layer to determine the next predicted value. We used root mean squared logarithmic errors (RMSLE) to compare the predicted and observed data, then recalculated the predictions again. Results: The result of our study underscores that the COVID19 pandemic is probably a propagated source epidemic, therefore repeated peaks on the epidemic curve (rise of the daily number of the newly diagnosed infections) are to be anticipated. The errors between the predicted and validated data and trends seems to be low. Conclusions: The influence of this pandemic is great worldwide, impact our everyday lifes. Especially decision makers must be aware, that even if strict public health measures are executed and sustained, future peaks of infections are possible. The AI based predictions might be useful tools for predictions and the models can be recalculated according to the new observed data, to get more precise forecast of the pandemic.

negative: Characterization of Influenza A Virus Infection in Mouse Pulmonary Stem/Progenitor Cells The pulmonary stem/progenitor cells, which could be differentiated into downstream cells to repair tissue damage caused by influenza A virus, have also been shown to be the target cells of influenza virus infection. In this study, mouse pulmonary stem/progenitor cells (mPSCs) with capability to differentiate into type I or type II alveolar cells were used as an in vitro cell model to characterize replication and pathogenic effects of influenza viruses in PSCs. First, mPSCs and its immortalized cell line mPSCs(Oct4+) were shown to be susceptible to PR8, seasonal H1N1, 2009 pandemic H1N1, and H7N9 influenza viruses and can generate infectious virus particles, although with a lower virus titer, which could be attributed by the reduced vRNA replication and nucleoprotein (NP) aggregation in the cytoplasm. Nevertheless, a significant increase of interleukin (IL)-6 and interferon (IFN)-γ at 12 h and IFN-β at 24 h post infection in mPSCs implicates that mPSCs might function as a sensor to modulate immune responses to influenza virus infection. In summary, our results demonstrated mPSCs, as one of the target cells for influenza A viruses, could modulate early proinflammatory responses to influenza virus infection.

negative: Lessons unfolding from pediatric cases of COVID‐19 disease caused by SARS‐CoV‐2 infection

negative: Predictions, role of interventions and effects of a historic national lockdown in India's response to the COVID-19 pandemic: data science call to arms Importance: India has taken strong and early public health measures for arresting the spread of the COVID-19 epidemic. With only 536 COVID-19 cases and 11 fatalities, India - a democracy of 1.34 billion people - took the historic decision of a 21-day national lockdown on March 25. The lockdown was further extended to May 3, soon after the analysis of this paper was completed. Objective: To study the short- and long-term impact of an initial 21-day lockdown on the total number of COVID-19 cases in India compared to other less severe non-pharmaceutical interventions using epidemiological forecasting models and Bayesian estimation algorithms; to compare effects of hypothetical durations of lockdown from an epidemiological perspective; to study alternative explanations for slower growth rate of the virus outbreak in India, including exploring the association of the number of cases and average monthly temperature; and finally, to outline the pivotal role of reliable and transparent data, reproducible data science methods, tools and products as we reopen the country and prepare for a post lock-down phase of the pandemic. Design, Setting, and Participants: We use the daily data on the number of COVID-19 cases, of recovered and of deaths from March 1 until April 7, 2020 from the 2019 Novel Coronavirus Visual Dashboard operated by the Johns Hopkins University Center for Systems Science and Engineering (JHU CSSE). Additionally, we use COVID-19 incidence counts data from Kaggle and the monthly average temperature of major cities across the world from Wikipedia. Main Outcome and Measures: The current time-series data on daily proportions of cases and removed (recovered and death combined) from India are analyzed using an extended version of the standard SIR (susceptible, infected, and removed) model. The eSIR model incorporates time-varying transmission rates that help us predict the effect of lockdown compared to other hypothetical interventions on the number of cases at future time points. A Markov Chain Monte Carlo implementation of this model provided predicted proportions of the cases at future time points along with credible intervals (CI). Results: Our predicted cumulative number of COVID-19 cases in India on April 30 assuming a 1-week delay in people's adherence to a 21-day lockdown (March 25 - April 14) and a gradual, moderate resumption of daily activities after April 14 is 9,181 with upper 95% CI of 72,245. In comparison, the predicted cumulative number of cases under "no intervention" and "social distancing and travel bans without lockdown" are 358 thousand and 46 thousand (upper 95% CI of nearly 2.3 million and 0.3 million) respectively. An effective lockdown can prevent roughly 343 thousand (upper 95% CI 1.8 million) and 2.4 million (upper 95% CI 38.4 million) COVID-19 cases nationwide compared to social distancing alone by May 15 and June 15, respectively. When comparing a 21-day lockdown with a hypothetical lockdown of longer duration, we find that 28-, 42-, and 56-day lockdowns can approximately prevent 238 thousand (upper 95% CI 2.3 million), 622 thousand (upper 95% CI 4.3 million), 781 thousand (upper 95% CI 4.6 million) cases by June 15, respectively. We find some suggestive evidence that the COVID-19 incidence rates worldwide are negatively associated with temperature in a crude unadjusted analysis with Pearson correlation estimates [95% confidence interval] between average monthly temperature and total monthly incidence around the world being -0.185 [-0.548, 0.236] for January, -0.110 [-0.362, 0.157] for February, and -0.173 [-0.314, -0.026] for March. Conclusions and Relevance: The lockdown, if implemented correctly in the end, has a high chance of reducing the total number of COVID-19 cases in the short term, and buy India invaluable time to prepare its healthcare and disease monitoring system. Our analysis shows we need to have some measures of suppression in place after the lockdown for the best outcome. We cannot heavily rely on the hypothetical prevention governed by meteorological factors such as temperature based on current evidence. From an epidemiological perspective, a longer lockdown between 42-56 days is preferable. However, the lockdown comes at a tremendous price to social and economic health through a contagion process not dissimilar to that of the coronavirus itself. Data can play a defining role as we design post-lockdown testing, reopening and resource allocation strategies. Software: Our contribution to data science includes an interactive and dynamic app (covind19.org) with short- and long-term projections updated daily that can help inform policy and practice related to COVID-19 in India. Anyone can visualize the observed data for India and create predictions under hypothetical scenarios with quantification of uncertainties. We make our prediction codes freely available (https://github.com/umich-cphds/cov-ind-19) for reproducible science and for other COVID-19 affected countries to use them for their prediction and data visualization work.

negative: The One Health Concept: 10 Years Old and a Long Road Ahead Over the past decade, a significant increase in the circulation of infectious agents was observed. With the spread and emergence of epizootics, zoonoses, and epidemics, the risks of pandemics became more and more critical. Human and animal health has also been threatened by antimicrobial resistance, environmental pollution, and the development of multifactorial and chronic diseases. This highlighted the increasing globalization of health risks and the importance of the human–animal–ecosystem interface in the evolution and emergence of pathogens. A better knowledge of causes and consequences of certain human activities, lifestyles, and behaviors in ecosystems is crucial for a rigorous interpretation of disease dynamics and to drive public policies. As a global good, health security must be understood on a global scale and from a global and crosscutting perspective, integrating human health, animal health, plant health, ecosystems health, and biodiversity. In this study, we discuss how crucial it is to consider ecological, evolutionary, and environmental sciences in understanding the emergence and re-emergence of infectious diseases and in facing the challenges of antimicrobial resistance. We also discuss the application of the “One Health” concept to non-communicable chronic diseases linked to exposure to multiple stresses, including toxic stress, and new lifestyles. Finally, we draw up a list of barriers that need removing and the ambitions that we must nurture for the effective application of the “One Health” concept. We conclude that the success of this One Health concept now requires breaking down the interdisciplinary barriers that still separate human and veterinary medicine from ecological, evolutionary, and environmental sciences. The development of integrative approaches should be promoted by linking the study of factors underlying stress responses to their consequences on ecosystem functioning and evolution. This knowledge is required for the development of novel control strategies inspired by environmental mechanisms leading to desired equilibrium and dynamics in healthy ecosystems and must provide in the near future a framework for more integrated operational initiatives.

negative: How Could This Happen?: Narrowing Down the Contagion of COVID-19 and Preventing Acute Respiratory Distress Syndrome (ARDS) In this rapid commentary, a mini-review is given of the present state-of-knowledge regarding the etiology and epidemiology of the new coronavirus 2019-nCoV and the risks for developing Acute respiratory distress syndrome (ARDS). The available knowledge on the viral genomics, molecular biology and pathogenicity of viruses of the Coronaviridae family and other Nidovirales, forms a helpful template for understanding the present pandemic outbreak. However, important questions remain unanswered about the underlying mechanism causing the very high case fatality ratios (CFR) and mechanisms regarding severe reactions like ARDS, fatal cardiac and renal failures, associated with a number of important comorbidity factors. Immunological reactions to lung alveoles in particular (involving lung macrophages and alveolar epithelial cell damage) in late phase ARDS in SARS-like CoV diseases, so far may not have received enough attention. Finally a shortlist of questions for high priority further research is suggested.

negative: Transmission dynamics of 2019 novel coronavirus (2019-nCoV) Background Since December 29, 2019, pneumonia infection with 2019-nCoV has rapidly spread out from Wuhan, Hubei Province, China to most others provinces and other counties. However, the transmission dynamics of 2019-nCoV remain unclear. Methods Data of confirmed 2019-nCoV cases before January 23, 2020 were collected from medical records, epidemiological investigations or official websites. Data of severe acute respiratory syndrome (SARS) cases in Guangdong Province during 2002-2003 were obtained from Guangdong Provincial Center for Disease Control and Prevention (GDCDC). Exponential Growth (EG) and maximum likelihood estimation (ML) were applied to estimate the reproductive number (R) of 2019-nCoV and SARS. Findings As of January 23, 2020, a total of 830 confirmed 2019-nCoV cases were identified across China, and 9 cases were reported overseas. The average incubation duration of 2019-nCoV infection was 4.8days. The average period from onset of symptoms to isolation of 2019-nCoV and SARS cases were 2.9 and 4.2 days, respectively. The R values of 2019-nCoV were 2.90 (95%CI: 2.32-3.63) and 2.92 (95%CI: 2.28-3.67) estimated using EG and ML respectively, while the corresponding R values of SARS-CoV were 1.77 (95%CI: 1.37-2.27) and 1.85 (95%CI: 1.32-2.49). We observe a decreasing trend of the period from onset to isolation and R values of both 2019-nCoV and SARS-CoV. Interpretation The 2019-nCoV may have a higher pandemic risk than SARS broken out in 2003. The implemented public-health efforts have significantly decreased the pandemic risk of 2019-nCoV. However, more rigorous control and prevention strategies and measures to contain its further spread. Funding National Key Research and Development Program of China, Science and Technology Program of Guangdong Province, and Guangzhou Science and technology Plan Project.

negative: Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.

negative: COVID-19: The first documented coronavirus pandemic in history The novel human coronavirus disease COVID-19 has become the fifth documented pandemic since the 1918 flu pandemic. COVID-19 was first reported in Wuhan, China, and subsequently spread worldwide. The coronavirus was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses based on phylogenetic analysis. SARS-CoV-2 is believed to be a spillover of an animal coronavirus and later adapted the ability of human-to-human transmission. Because the virus is highly contagious, it rapidly spreads and continuously evolves in the human population. In this review article, we discuss the basic properties, potential origin, and evolution of the novel human coronavirus. These factors may be critical for studies of pathogenicity, antiviral designs, and vaccine development against the virus.

negative: Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13 The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.

negative: Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology

negative: Guinea Fowl Coronavirus Diversity Has Phenotypic Consequences for Glycan and Tissue Binding Guinea fowl coronavirus (GfCoV) causes fulminating enteritis that can result in a daily death rate of 20% in guinea fowl flocks. Here, we studied GfCoV diversity and evaluated its phenotypic consequences. Over the period of 2014 to 2016, affected guinea fowl flocks were sampled in France, and avian coronavirus presence was confirmed by PCR on intestinal content and immunohistochemistry of intestinal tissue. Sequencing revealed 89% amino acid identity between the viral attachment protein S1 of GfCoV/2014 and that of the previously identified GfCoV/2011. To study the receptor interactions as a determinant for tropism and pathogenicity, recombinant S1 proteins were produced and analyzed by glycan and tissue arrays. Glycan array analysis revealed that, in addition to the previously elucidated biantennary di-N-acetyllactosamine (diLacNAc) receptor, viral attachment S1 proteins from GfCoV/2014 and GfCoV/2011 can bind to glycans capped with alpha-2,6-linked sialic acids. Interestingly, recombinant GfCoV/2014 S1 has an increased affinity for these glycans compared to that of GfCoV/2011 S1, which was in agreement with the increased avidity of GfCoV/2014 S1 for gastrointestinal tract tissues. Enzymatic removal of receptors from tissues before application of spike proteins confirmed the specificity of S1 tissue binding. Overall, we demonstrate that diversity in GfCoV S1 proteins results in differences in glycan and tissue binding properties. IMPORTANCE Avian coronaviruses cause major global problems in the poultry industry. As causative agents of huge economic losses, the detection and understanding of the molecular determinants of viral tropism are of ultimate importance. Here, we set out to study those parameters and obtained in-depth insight into the virus-host interactions of guinea fowl coronavirus (GfCoV). Our data indicate that diversity in GfCoV viral attachment proteins results in differences in degrees of affinity for glycan receptors, as well as altered avidity for intestinal tract tissues, which might have consequences for GfCoV tissue tropism and pathogenesis in guinea fowls.

negative: RNA helicase 3.6.4.13 EC number 3.6.4.13 Systematic name ATP phosphohydrolase (RNA helix unwinding) Recommended name RNA helicase Synonyms 1a NTPase/helicase <16> [5] ATP/dATP-dependent RNA helicase <1,42> [32] ATPase <10,12> [1,36] ATPase/RNA helicase <1,42> [32] ATPase/helicase <10> [36,41] BMV 1a protein <16> [5] BmL3-helicase <1,42> [32] Brr2p <6> [50] DBP2 <24> [30] DDX17 <33> [12] DDX19 <43> [56] DDX25 <23,34,35> [12,21] DDX3 <25> [8] DDX3X <25> (<25> the gene is localized to the X chromosome [12]) [12] DDX3Y <29> (<29> the gene is localized to the Y chromosome [12]) [12] DDX4 <30> [12] DDX5 <32> [12] DEAD box RNA helicase <1,2,3> [32,45,52] DEAD box helicase <2> [45] DEAD-box RNA helicase <4,5,7,38,47,48> [9,14,16,25,53,55] DEAD-box protein DED1 <38> [11] DEAD-box rRNA helicase <5> [26] DEAH-box RNA helicase <24> [30] DEAH-box protein 2 <24> [30] DED1 <38> [11,14] DENV NS3H <10> [41] DEXD/H-box RNA helicase <43> [56] DEx(H/D)RNA helicase <12> [23] DHX9 <44> [58] DbpA <5> [10,25,26] Dhx9/RNA helicase A <13> [61] EhDEAD1 <7> [16] EhDEAD1 RNA helicase <7> [16] FRH <9> [54] FRQ-interacting RNA helicase <9> [54] GRTH <3> [57] GRTH/DDX25 <3,35> [21,51] HCV NS3 helicase <12> [48] KOKV helicase <27> [7] Mtr4p <31> [22] NPH-II <8> [18,28] NS3 <10,12,17,20,39,41> (<12,39> ambiguous [27,42,44]) [1,2,4,27,35,36,39, 42,44,46] NS3 ATPase/helicase <10> [41] NS3 NTPase/helicase <17> (<17> ambiguous [46]) [46] NS3 helicase <10,12,17> [15,44,46] NS3 protein <10,12,17,18> (<12> ambiguous [39]) [15,39,40,41,62] NTPase/helicase <12> (<12> ambiguous [37]) [37,39] RHA <6> [31,49] RNA helicase <2> [45] RNA helicase A <6,44> [31,49,58] RNA helicase CrhR <14> [59] RNA helicase DDX3 <25> [8] RNA helicase Ddx39 <47> [53] RNA helicase Hera <4> [9] RNA-dependent ATPase <37> [34] RNA-dependent NTPase/helicase <12> [1] RTPase <10> [36] RhlB <5> [43] SpolvlgA <48> [55] Supv3L1 <46> [64] TGBp1 NTPase/helicase domain <22,28> [24] Tk-DeaD <15> [47] VRH1 <26> [33] YxiN <2> [45] eIF4A <36> [20] eIF4A helicase <36> [20] eIF4AIII <37> [34] eukaryotic initiation factor eIF 4A <36> [20] gonadotropin-regulated testicular RNA helicase <3> [51,57] helicase <10> [41] helicase B <5> [43] helicase/nucleoside triphosphatase <10> [4] non structural protein 3 <12> (<12> ambiguous [37,38]) [37,38] non-structural 3 <10> [36] non-structural protein 3 <17> [46] non-structural protein 3 protein <18> [40] nonstructural protein 3 <12,17,20,39,40,41> (<12,17,39,40> ambiguous [6,27, 39,42,44,46]) [1,2,6,27,35,39,42,44,46] nucleoside 5’-triphosphatase <10> [4] nucleoside triphosphatase/RNA helicase and 5’-RNA triphosphatase <20> [2] nucleoside triphosphatase/helicase <16> [5] p54 RNA helicase <45> [60] p68 RNA helicase <3,6> [52,63] protein NS3 <12> (<12> ambiguous [38]) [38]

negative: Long-term viremia and fecal shedding in pups after modified-live canine parvovirus vaccination Canine parvovirus (CPV) modified live virus vaccines are able to infect vaccinated dogs replicating in the bloodstream and enteric mucosa. However, the exact duration and extent of CPV vaccine-induced viremia and fecal shedding are not known. With the aim to fill this gap, 26 dogs were administered two commercial vaccines containing a CPV-2 or CPV-2b strain and monitored for 28 days after vaccination. By using real-time PCR, vaccine-induced viremia and shedding were found to be long lasting for both vaccinal strains. Vaccinal CPV-2b shedding was detected for a shorter period than CPV-2 (12 against 19 mean days) but with greater viral loads, whereas viremia occurred for a longer period (22 against 19 mean days) and with higher titers for CPV-2b. Seroconversion appeared as early as 7 and 14 days post-vaccination for CPV-2b and CPV-2 vaccines, respectively. With no vaccine there was any diagnostic interference using in-clinic or hemagglutination test, since positive results were obtained only by fecal real-time PCR testing. The present study adds new insights into the CPV vaccine persistence in the organism and possible interference with diagnostic tests.

negative: Influenza A Virus Entry Inhibitors Targeting the Hemagglutinin Influenza A virus (IAV) has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA), the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Here we reviewed the recent progress in the study of conformational changes of HA during viral fusion process and the development of HA-based IAV entry inhibitors, which may provide a new choice for controlling future influenza pandemics.

negative: Mortality burden from seasonal influenza in Chongqing, China, 2012-2018. Purpose: To estimate influenza-associated excess mortality rates (EMRs) in Chongqing from 2012 to 2018.Methods: We obtained weekly mortality data for all-cause and four underlying causes of death (circulatory and respiratory disease (CRD), pneumonia and influenza (P&I), chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IDH)), and influenza surveillance data, from 2012 to 2018. A negative-binomial regression model was used to estimate influenza-associated EMRs in two age groups (<65 years and ≥65 years).Results: It was estimated that an annual average of 10025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths. The average EMR for all-cause death associated with influenza was 33.5 (95% confidence interval (CI): 31.5-35.6) per 100 000 persons, and in separate cause-specific models we attributed 24.7 (95% CI: 23.3-26.0), 0.8 (95% CI: 0.7-0.8), 8.5 (95% CI: 8.1-9.0) and 5.0 (95% CI: 4.7-5.3) per 100 000 persons EMRs to CRD, P&I, COPD and IDH, respectively. The estimated EMR for influenza B virus was 20.6 (95% CI: 20.3-21.0), which was significantly higher than the rates of 5.3 (95% CI: 4.5-6.1) and 7.5 (95% CI: 6.7-8.3) for A(H3N2) and A(H1N1) pdm09 virus, respectively. The estimated EMR was 152.3 (95% CI: 136.1-168.4) for people aged ≥65 years, which was significantly higher than the rate for those aged <65 years (6.8, 95% CI: 6.3-7.2).Conclusions: Influenza was associated with substantial EMRs in Chongqing, especially among elderly people. Influenza B virus caused a relatively higher excess mortality impact compared with A(H1N1)pdm09 and A(H3N2). It is advisable to optimize future seasonal influenza vaccine reimbursement policy in Chongqing to curb disease burden.

negative: RNA structure interactions and ribonucleoprotein processes of the influenza A virus In one more years, we will ‘celebrate’ an exact centenary of the Spanish flu pandemic. With the rapid evolution of the influenza virus, the possibility of novel pandemic remains ever a concern. This review covers our current knowledge of the influenza A virus: on the role of RNA in translation, replication, what is known of the expressed proteins and the protein products generated from alternative splicing, and on the role of base pairing in RNA structure. We highlight the main events associated with viral entry into the cell, the transcription and replication process, an export of the viral genetic material from the nucleus and the final release of the virus. We discuss the observed potential roles of RNA secondary structure (the RNA base-pairing arrangement) and RNA/RNA interactions in this scheme.

negative: The Pandemic of Hate is Giving COVID-19 a Helping Hand The Pandemic of Hate Is Giving Novel Coronavirus Disease (COVID-19) a Helping Hand.

negative: The Human Coronaviruses The human coronaviruses have been shown to be a major player in clinical microbiology and frequently occur as pathogens responsible for mild to severe respiratory infections. Moreover, two of the most dangerous viral respiratory infections are caused by novel coronaviruses, namely, the SARS and the MERS coronavirus. This chapter briefly summarizes the most important facts and knowledge required for the appropriate laboratory diagnostics of infections caused by the human coronaviruses.

negative: Serological relation between calf diarrhea coronavirus and hemagglutinating encephalomyelitis virus Neutralizing (NT) and hemagglutination-inhibiting (HI) antibodies to calf diarrhea coronavirus (CDCV) and hemagglutinating encephalomyelitis virus of swine (HEV) (strain 67 N) were detected in high proportions of normal adult cattle and pigs in Japan. Since comparison of NT and HI titers in the serum samples suggested an antigenic difference between the viruses, cross NT and HI tests of these viruses were carried out with antisera raised in rabbits. The homologous NT titers were markedly higher than the heterologous titers. In HI tests essentially the same results were obtained. These findings indicate the presence of a marked difference in antigenic make-up between CDCV and HEV. NT and HI tests can clearly differentiate the viruses, although there is some cross reaction.

negative: A Tale of Two Communities: Characterizing Reddit Response to COVID-19 through /r/China_Flu and /r/Coronavirus The COVID-19 pandemic has deeply impacted people's lives around the globe. During the extended lockdowns caused by the pandemic, online communities are crucial for people to access information and share experiences. In particular, two"new"communities have emerged on Reddit: /r/China_flu and /r/Coronavirus. By studying activities and users in these two communities, we provide a characterization of people's responses to COVID-19 on Reddit. First, we find that user activity peaks around March 17, when the World Health Organization (WHO) announced COVID-19 as a pandemic. Shortly after that, the activity levels of both communities have been declining week by week. We further illustrate the central role of these two communities in the emergence of COVID-related communities. Second, we study the differences between these two communities. /r/Coronavirus is recommended as the official community for COVID-19 on Reddit, while /r/China_flu adopts a loose moderation practice. As a result, we observe that these two communities are gradually growing apart and more extremism is being found in /r/China_flu. Finally, we examine the spillover effect of the COVID-19 pandemic on user activity across the entire Reddit platform. Our results show significant changes in user activities outside COVID-related communities. In subreddits related to finance, food, and countries/cities, user activity is recovering to the pre-pandemic level in late April and May as countries reopen, but subreddits related to travel and sports remain highly impacted and show lower activity levels than the pre-pandemic period. Our work highlights the strength of Reddit as a source for understanding public reactions to COVID-19 and the importance of content moderation on the Internet during a pandemic.

negative: Future Pandemic Influenza Virus Detection Relies on the Existing Influenza Surveillance Systems: A Perspective from Australia and New Zealand The anniversary of the 1918–1919 influenza pandemic has allowed a refocusing on the global burden of influenza and the importance of co-ordinated international surveillance for both seasonal influenza and the identification of control strategies for future pandemics. Since the introduction of the International Health Regulations (IHR), progress had been slow, until the emergence of the novel influenza A(H1N1)2009 virus and its global spread, which has led to the World Health Organization (WHO) developing a series of guidance documents on global influenza surveillance procedures, severity and risk assessments, and essential measurements for the determination of national pandemic responses. However, the greatest burden of disease from influenza occurs between pandemics during seasonal influenza outbreaks and epidemics. Both Australia and New Zealand utilise seasonal influenza surveillance to support national influenza awareness programs focused on seasonal influenza vaccination education and promotion. These programs also serve to promote the importance of pandemic preparedness.

negative: Roles of meteorological conditions in COVID-19 transmission on a worldwide scale The novel coronavirus (SARS-CoV-2/ 2019-nCoV) identified in Wuhan, China, in December 2019 has caused great damage to public health and economy worldwide with over 140,000 infected cases up to date. Previous research has suggested an involvement of meteorological conditions in the spread of droplet-mediated viral diseases, such as influenza. However, as for the recent novel coronavirus, few studies have discussed systematically about the role of daily weather in the epidemic transmission of the virus. Here, we examine the relationships of meteorological variables with the severity of the outbreak on a worldwide scale. The confirmed case counts, which indicates the severity of COVID-19 spread, and four meteorological variables, i.e., air temperature, relative humidity, wind speed, and visibility, were collected daily between January 20 and March 11 (52 days) for 430 cities and districts all over China, 21 cities/ provinces in Italy, 21 cities/ provinces in Japan, and 51 other countries around the world. Four different time delays of weather (on the day, 3 days ago, 7 days ago, and 14 days ago) as to the epidemic situation were taken for modeling and we finally chose the weather two weeks ago to model against the daily epidemic situation as its correlated with the outbreak best. Taken Chinese cities as a discovery dataset, it was suggested that temperature, wind speed, and relative humidity combined together could best predict the epidemic situation. The meteorological model could well predict the outbreak around the world with a high correlation (r2>0.6) with the real data. Using this model, we further predicted the possible epidemic situation in the future 12 days in several high-latitude cities with potential outbreak. This model could provide more information for government's future decisions on COVID-19 outbreak control.

negative: Variable computed tomography appearances of COVID-19. The coronavirus disease 2019 (COVID-19) is typically diagnosed by specific assays that detect viral nucleic acid from the upper respiratory tract; however, this may miss infections involving only the lower airways. Computed tomography (CT) has been described as a diagnostic modality in the COVID-19 diagnosis and treatment plan. We present a case series with virologically confirmed COVID-19 pneumonia. Variable CT features were observed: consolidation with ground-glass opacities, ground-glass opacities with subpleural reticular bands, and an anterior-posterior gradient of lung abnormalities resembling that of acute respiratory distress syndrome. In one patient, we noted evolution of CT findings, where there was interval resolution of bilateral lung consolidation with development of bronchiolectasis and subpleural fibrotic bands. While sensitive for detecting lung parenchymal abnormalities in COVID-19 pneumonia, CT for initial diagnosis is discouraged and should be reserved for specific clinical indications. Interpretation of chest CT findings should be correlated with duration of symptoms to better determine the disease stage and aid in patient management.

negative: The Late Arrival of COVID-19 in Africa - Mitigating Pan-Continental Spread

negative: Viral load in patients infected with pandemic H1N1 2009 influenza A virus Viral shedding profile of infections caused by the pandemic H1N1 2009 influenza A virus has not been reported. The aim of this study was to determine the viral load in different body sites. Viral loads of pandemic H1N1 virus in respiratory specimens, stool, urine, and serum were determined by quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). Respiratory specimens from patients with seasonal influenza were used as historical controls. Initial pre‐treatment viral load were compared between these two groups. Serial respiratory specimens from patients with pandemic H1N1 virus infection were obtained for analysis of viral dynamics. Twenty‐two pandemic H1N1 cases and 44 seasonal influenza historical controls were included. The mean initial viral load before oseltamivir therapy was 1.84 × 10(8) copies/ml for pandemic H1N1 virus compared with 3.28 × 10(8) copies/ml in seasonal influenza historical controls (P = 0.085). Among patients with pandemic H1N1 virus infection, peak viral load occurred on the day of onset of symptoms, and declined gradually afterwards, with no virus being detectable in respiratory specimens by RT‐PCR 8 days and by culture 5 days after the onset of symptoms respectively, except in one patient. Pandemic H1N1 virus was detected in stool and in urine from 4/9 and 1/14 patients, respectively. Viral culture was also positive from the stool sample with the highest viral load. Younger age was associated with prolonged shedding in the respiratory tract and higher viral load in the stool. Data from this quantitative analysis of viral shedding may have implications for formulating infection control measures. J. Med. Virol. 82:1–7, 2010. © 2009 Wiley‐Liss, Inc.

negative: Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes severe respiratory illness in humans, which eventually results in the current outbreak of novel coronavirus disease (COVID-19) around the world. The research community is interested to know what are the hotspots in coronavirus (CoV) research and how much is known about COVID-19. This study aimed to evaluate the characteristics of publications involving coronaviruses as well as COVID-19 by using a topic modeling analysis. Methods: We extracted all abstracts and retained the most informative words from the COVID-19 Open Research Dataset, which contains all the 35,092 pieces of coronavirus related literature published up to March 20, 2020. Using Latent Dirichlet Allocation modeling, we trained an eight-topic model from the corpus. We then analyzed the semantic relationships between topics and compared the topic distribution between COVID-19 and other CoV infections. Results: Eight topics emerged overall: clinical characterization, pathogenesis research, therapeutics research, epidemiological study, virus transmission, vaccines research, virus diagnostics, and viral genomics. It was observed that COVID-19 research puts more emphasis on clinical characterization, epidemiological study, and virus transmission at present. In contrast, topics about diagnostics, therapeutics, vaccines, genomics and pathogenesis only accounted for less than 10% or even 4% of all the COVID-19 publications, much lower than those of other CoV infections. Conclusions: These results identified knowledge gaps in the area of COVID-19 and offered directions for future research. Keywords: COVID-19, coronavirus, topic modeling, hotspots, text mining

negative: Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control.

negative: The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.

negative: Respiratory viral infections post-lung transplantation Community-acquired respiratory viruses (CARVs) are common pathogens in lung transplant recipients. Infection due to these viruses is associated with multiple complications including: rhinitis, pharyngitis, bronchitis, pneumonia, respiratory failure and even death. CARVs have also become increasingly recognized as a risk factor for acute rejection (AR) and bronchiolitis obliterans syndrome (BOS). Newer diagnostic techniques have enhanced the accuracy of diagnosis, but proven treatment options for CARVs are limited. Further insight into the immune response and allograft dysfunction associated with CARV infections is needed in order to develop novel management strategies which can reduce the morbidity and mortality caused by these infectious agents.

negative: Phylogenetic analysis of human coronavirus NL63 circulating in Italy Abstract Background Five known human coronaviruses infect the human respiratory tract: HCoV-OC43, HCoV-229E, SARS-CoV, HCoV-NL63 and HCoV-HKU1. Objectives To evaluate the prevalence of HCoV-NL63 in hospitalized adult patients and to perform molecular characterization of Italian strains. Study Design HCoV-NL63 was sought by RT-PCR in 510 consecutive lower respiratory tract (LRT) samples, collected from 433 Central-Southern Italy patients over a 1-year period. Phylogenetic analysis was performed by partial sequencing of S and ORF1a. Additional S sequences from Northern Italy were included in the phylogenetic trees. Results HCoV-NL63 was detected in 10 patients (2.0%) with symptomatic respiratory diseases, mainly during winter. Phylogenetic analysis indicated a certain degree of heterogeneity in Italian isolates. The ORF1a gene clustering in phylogenetic trees did not match with that of the S gene. Conclusions As observed by others, HCoV-NL63 is often associated with another virus. Phylogenetic characterization of HCoV-NL63 circulating in Italy indicates that this virus circulates as a mixture of variant strains, as observed in other countries.

negative: COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza’s characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.

negative: The burden of laboratory-confirmed influenza infection in Lebanon between 2008 and 2016: a single tertiary care center experience BACKGROUND: Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon. METHODS: A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis. RESULTS: A total of 1829 cases of laboratory-confirmed influenza were identified. Average annual positivity rate was 14% (positive tests over total requested). Both influenza A and B co-circulated in each season with predominance of influenza A. Influenza virus started circulating in December and peaked in January and February. The age group of 19–50 years accounted for the largest proportion of cases (22.5%) followed by the age group of 5–19 years (18%). Pneumonia was the most common complication reported in 33% of cases. Mortality reached 3.8%. The two extremes of age (< 2 years and ≥ 65 years) were associated with a more severe course of disease, hospitalization, intensive care unit (ICU) admission, complications, and mortality rate. Of all the identified cases, 26% were hospitalized. Moderate-to-severe disease was more likely in influenza B cases but no difference in mortality was reported between the two types. Antivirals were prescribed in 68.8% and antibiotics in 41% of cases. There seemed to be an increasing trend in the number of diagnosed and hospitalized cases over the years of the study. CONCLUSION: Patients with laboratory-confirmed influenza at our center had a high rate of hospitalization and mortality. A population based prospective surveillance study is needed to better estimate the burden of Influenza in Lebanon that would help formulate a policy on influenza control.

negative: Influence of exogenous gonadotropin-releasing hormone on seasonal reproductive behavior of the coyote (Canis latrans) Wild Canis species such as the coyote (C. latrans) express a suite of reproductive traits unusual among mammals, including perennial pair-bonds and paternal care of the young. Coyotes also are monestrous, and both sexes are fertile only in winter; thus, they depend upon social and physiologic synchrony for successful reproduction. To investigate the mutability of seasonal reproduction in coyotes, we attempted to evoke an out-of-season estrus in October using one of two short-acting gonadotropin-releasing hormone (GnRH) agents: (1) a GnRH analogue, deslorelin (6-d-tryptophan-9-(N-ethyl-l-prolinamide)-10-deglycinamide), 2.1 mg pellet sc; or (2) gonadorelin, a GnRH (5-oxoPro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyNH(2)) porcine hypothalamic extract, 2.0 μg/kg im once daily for 3 consecutive days. A transient increase in serum concentrations of estradiol and progesterone (1 and 2 wk, respectively) was detected after treatment with deslorelin but not gonadorelin. Also, socio-sexual behaviors reminiscent of winter mating (including courtship, mate-guarding, precoital mounts, and copulatory ties) were observed among the deslorelin group. During the subsequent breeding season (January and February), however, preovulatory courtship behavior and olfactory sampling appeared suppressed; emergence of mounts and copulations were delayed in both deslorelin and gonadorelin treatment groups. Furthermore, whereas 8 of 12 females treated in October ovulated and produced healthy litters in the spring, 4 naïve coyotes failed to copulate or become pregnant. Thus, perturbation of hormones prior to ovulation in species with complex mating behaviors may disrupt critical intrapair relationships, even if fertility is not impaired physiologically.

negative: Global seasonal occurrence of middle east respiratory syndrome coronavirus (MERS-CoV) infection. OBJECTIVE Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an evolving global health crisis. Despite recent efforts, there are numerous notable gaps in the understanding of MERS-CoV seasonal diversity. We aimed at investigating the global seasonal occurrence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreaks. MATERIALS AND METHODS We obtained the data on the prevalence and occurrence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection from the World Health Organization (WHO) for all the MERS cases reported from the various countries and their allied ministries. We also recorded the research documents published in various global scientific journals on the seasonal occurrence of MERS-CoV infection during the period 2012-2017. RESULTS Worldwide 2048 laboratory confirmed cases of MERS-CoV infection were reported from June 2012 to the Dec 2017. 1680 (82.03%) cases were from the Saudi Arabia and 368 (17.96%) cases were reported from the other countries of the world. The maximum number of cases reported in June was 474 (23.14%). 287 (14.01%) cases were reported from Saudi Arabia and remaining 187 (9.13%) cases were reported from all over the world. The number of cases reported from April to June was 396 (19.33%) while the cases encountered from October to December were 231 (11.27%). CONCLUSIONS The highest global seasonal occurrence of Middle East Respiratory Syndrome coronavirus-MERS-CoV outbreak cases were found in the month of June, while the lowest was found in the month of January during the period of 2012 to 2017. The pattern of MERS-CoV infections has been observed to have seasonal variations. It is suggested that the health officials should highlight the seasonal occurrence of MERS-CoV outbreak and take better preventive measures to minimize the disease burden nationally and globally.

negative: Pathogens shape sex differences in mammalian aging ABSTRACT Understanding the origin of sex differences in lifespan and aging patterns remains a salient challenge in both biogerontology and evolutionary biology. Different factors have been studied but the potential influence of pathogens has never been investigated. Sex differences especially in hormones and resource allocation generate a differential response to pathogens and thereby shape sex differences in lifespan or aging. We provide an integrative framework linking host pathogenic environment with both sex-specific selections on immune performance and mortality trajectories. We propose future directions to fill existing knowledge gaps about mechanisms that link sex differences, not only to exposition and sensitivity to pathogens, but also to mortality patterns, whilst emphasizing the urgent need to consider the role of sex in medicine.

negative: Beyond the Routine Influenza Surveillance

negative: Hospital-based Influenza Morbidity and Mortality (HIMM) Surveillance for A/H7N9 Influenza Virus Infection in Returning Travelers Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system began a H7N9 influenza surveillance scheme for returning travelers in addition to pre-existing emergency room (ER)-based influenza-like illness (ILI) surveillance and severe acute respiratory infection (SARI) surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is considered to have the highest pandemic potential among currently circulating influenza viruses. During the study period between October 1st, 2013 and April 30th, 2016, 11 cases presented with ILI within seven days of travel return. These patients visited China, Hong Kong, or neighboring Southeast Asian countries, but none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among 11) was the most common cause of ILI among returning travelers, and avian A/H7N9 influenza virus was not detected during the study period.

negative: Sensitivity and specificity of in vitro diagnostic device used for influenza rapid test in Taiwan Abstract The pandemic influenza A/H1N1 outbreak resulted in 18,449 deaths in over 214 countries. In Taiwan, the influenza rapid test, an in vitro diagnostic device (Flu-IVD), only requires documented reviews for market approval by the Taiwan Food and Drug Administration. The purpose of this study was to investigate the analytical sensitivity and specificity of Flu-IVDs used in Taiwan. Analytical sensitivity and specificity tests were performed for influenza antigens A/California/7/2009 (H1N1) virus, A/Victoria/210/2009 (H3N2) virus, B/Brisbane/60/08 virus, and human coronavirus OC43. A total of seven domestic and 31 imported Flu-IVD samples were collected, of which, 20 samples had inadequate labeling, including those with removed package inserts or incorrect insert information. The analytical sensitivity of Flu-IVDs for A/H1N1, A/H3N2, and Flu B was 500–1000 ng/mL, 1000 ng/mL, and 1000 ng/mL, respectively. For the 50% cell culture infective dose (CCID50) label, the average A/H1N1 and A/H3N2 sensitivity for Flu-IVDs was log10 5.8 ± 0.5 and log10 6.6 ± 0.5 CCID50/mL, respectively. As to the specificity test, no product cross-reacted with human coronavirus OC43. This study provides important information on the Flu-IVD regulation status and can thus help the government formulate policies for the regulation of in vitro diagnostic devices in Taiwan.

negative: A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features We first described the 2019 novel coronavirus infection in 10 children occurring in areas other than Wuhan. The coronavirus diseases in children are usually mild and epidemiological exposure is a key clue to recognize pediatric case. Prolonged virus shedding is observed in respiratory tract and feces at the convalescent stage.

negative: [Technologies and requirements of protection and disinfection in key places during COVID-19 outbreak]. COVID-19 a new respiratory infectious disease, has become an important public health problem. Inappropriate protection and disinfection measures are potential risk factors of transmission and outbreak of COVID-19 in key places. This theme issue is concerned with the prevention and control of COVID-19. Comprehensive measures and suggestions for protection and disinfection are put forward from perspectives of functional areas in key places, such as hotels, mobile cabin hospitals, passenger transport stations and public transport facilities, environment and facilities, personal protection, operation management system, etc., so as to provide technical support for the prevention and control of new respiratory infectious diseases.

negative: Influenza B virus infections in Western Saxony, Germany in three consecutive seasons between 2015 and 2018: Analysis of molecular and clinical features BACKGROUND: The impact of annual influenza epidemics and prevailing strains varies worldwide and regional. The majority of vaccines used contained two influenza A strains and only one influenza B strain (trivalent vaccine). AIM: The aim of the study was to compare laboratory confirmed influenza B cases during three consecutive years with respect to vaccination history, clinical symptoms and molecular virology. METHODS: Partial HA gene sequences were analyzed for lineage determination and complete HA sequence in cases with reported vaccination and in fatal cases. Clinical data were retrieved from patient charts. FINDINGS: During the 2015/16 season, 75 influenza B cases were retrieved; 11 in 2016/17, and 274 in 2017/18. The frequency of Yamagata-lineage strains increased from 7.6% to 100%. No difference was detected in the relative frequency of co-morbidities in season 2017/18. 37.7% of the adult patients and 4.5% of pediatric patients were vaccinated against influenza. INTERPRETATION: Phylogenetically, Yamagata strains clustered similarly in 2017/2018 when compared to the previous two influenza seasons. While the relative frequency of influenza B cases differed, the clinical symptoms remained similar. CONCLUSION: World Health Organization recommendations for the use of tetravalent vaccines that contain two influenza B strains (Yamagata and Victoria) in addition to the two influenza A strains (H1N1 and H3N2) should be implemented in national vaccination guidelines. FUNDING: This research was partially supported by the Association of Sponsors and Friends of Leipzig University.

negative: Clinical Effectiveness of Influenza Vaccination After Allogeneic Hematopoietic Stem Cell Transplantation: A Cross-sectional, Prospective, Observational Study BACKGROUND: Vaccination is the primary method for preventing influenza respiratory virus infection (RVI). Although the influenza vaccine is able to achieve serological responses in some allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, its clinical benefits are still uncertain. METHODS: In this prospective, cross-sectional study, we retrospectively analyzed the effect of inactivated trivalent influenza vaccination on the prevalence of influenza RVI in a consecutive cohort of 136 allo-HSCT adult recipients who developed 161 RVI over 5 flu seasons (from 2013 to 2018). Respiratory viruses in upper– and/or lower–respiratory tract specimens were tested using multiplex polymerase chain reaction panel assays. RESULTS: Overall, we diagnosed 74 episodes (46%) of influenza RVI in 70 allo-HSCT recipients. Influenza RVI occurred in 51% of the non-vaccinated compared to 36% of the vaccinated recipients (P = .036). A multivariate analysis showed that influenza vaccination was associated with a lower prevalence of influenza RVI (odds ratio [OR] 0.39, P = .01). A multivariate risk factor analysis of lower–respiratory tract disease (LRTD) identified 2 conditions associated with the probability of influenza RVI progression: influenza vaccination (OR 0.12, 95% confidence interval [CI] 0.014–1, P = .05) and a high-risk immunodeficiency score (OR 36, 95% CI 2.26–575, P = .011). Influenza vaccination was also associated with a lower likelihood of an influenza-related hospital admission (14% vs 2%, P = .04). CONCLUSIONS: This study shows that influenza vaccination may have a clinical benefit in allo-HSCT recipients with virologically-confirmed RVI, in terms of a lower influenza RVI prevalence, slower LRTD progression, and lower likelihood of hospital admission.

negative: Perceived risk, anxiety, and behavioural responses of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands: results of three consecutive online surveys BACKGROUND: Research into risk perception and behavioural responses in case of emerging infectious diseases is still relatively new. The aim of this study was to examine perceptions and behaviours of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands. METHODS: Two cross-sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15-19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above participating in a representative Internet panel were invited (survey 1, n = 456; survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1) time trends in risk perception, feelings of anxiety, and behavioural responses (survey 1-3) and 2) factors associated with taking preventive measures and strong intention to comply with government-advised preventive measures in the future (survey 3). RESULTS: Between May and August 2009, the level of knowledge regarding Influenza A (H1N1) increased, while perceived severity of the new flu, perceived self-efficacy, and intention to comply with preventive measures decreased. The perceived reliability of information from the government decreased from May to August (62% versus 45%). Feelings of anxiety decreased from May to June, and remained stable afterwards. From June to August 2009, perceived vulnerability increased and more respondents took preventive measures (14% versus 38%). Taking preventive measures was associated with no children in the household, high anxiety, high self-efficacy, more agreement with statements on avoidance, and paying much attention to media information regarding Influenza A (H1N1). Having a strong intention to comply with government-advised preventive measures in the future was associated with higher age, high perceived severity, high anxiety, high perceived efficacy of measures, high self-efficacy, and finding governmental information to be reliable. CONCLUSIONS: Decreasing trends over time in perceived severity and anxiety are consistent with the reality: the clinical picture of influenza turned out to be mild in course of time. Although (inter)national health authorities initially overestimated the case fatality rate, the public stayed calm and remained to have a relatively high intention to comply with preventive measures.

negative: A "One-Health" approach for diagnosis and molecular characterization of SARS-CoV-2 in Italy The current pandemic is caused by a novel coronavirus (CoV) called SARS-CoV-2 (species Severe acute respiratory syndrome-related coronavirus, subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae). In Italy, up to the 2nd of April 2020, overall 139,422 confirmed cases and 17,669 deaths have been notified, while 26,491 people have recovered. Besides the overloading of hospitals, another issue to face was the capacity to perform thousands of tests per day. In this perspective, to support the National Health Care System and to minimize the impact of this rapidly spreading virus, the Italian Ministry of Health involved the Istituti Zooprofilattici Sperimentali (IZSs), Veterinary Public Health Institutes, in the diagnosis of SARS-CoV-2 by testing human samples. IZSAM, is currently testing more than 600 samples per day and WGS from positive samples. Sequence analysis of these samples suggested that outbreaks in Abruzzo region may be related to outbreaks of northern Italy and northern Europe, these latter as for the presence of mutations in the N protein. CoVs, and related diseases, are well known to veterinarians since decades. The experience that veterinarians operating within the Public health system gained in the control and characterization of previous health issues of livestock and poultry including avian flu, bluetongue, foot and mouth disease, responsible for huge economic losses, is certainly of great help to minimize the impact of this global crisis.

negative: Ménage à trois of bacterial and viral pulmonary pathogens delivers coup de grace to the lung

negative: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020 On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged ≥65 years and particularly those aged ≥85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.

negative: How countries are using genomics to help avoid a second coronavirus wave.

negative: High coverage of influenza vaccination among healthcare workers can be achieved during heightened awareness of impending threat. INTRODUCTION As preparation against a possible avian flu pandemic, international and local health authorities have recommended seasonal influenza vaccination for all healthcare workers at geographical risk. This strategy not only reduces "background noise", but also chance of genetic shifts in avian influenza viruses when co-infection occurs. We evaluate the response of healthcare workers, stratified by professional groups, to a non-compulsory annual vaccination call, and make international comparisons with countries not at geographical risk. MATERIALS AND METHODS A cross-sectional study was performed over the window period for vaccination for the 2004 to 2005 influenza season (northern hemisphere winter). The study population included all adult healthcare workers (aged < or =21 years) employed by a large acute care tertiary hospital. RESULTS The uptake rates among frontline caregivers--doctors >50%, nurses >65% and ancillary staff >70%--markedly exceeded many of our international counterparts results. CONCLUSION Given its close proximity in time and space to the avian flu pandemic threat, Singapore healthcare workers responded seriously and positively to calls for preventive measures. Other factors, such as the removal of financial, physical and mental barriers, may have played important facilitative roles as well.

negative: Epidemiology and phylogenetic analysis of respiratory viruses from 2012 to 2015 – A sentinel surveillance report from union territory of Puducherry, India Abstract Background Acute respiratory infections (ARI) are the most common illnesses affecting people of all ages worldwide. Viruses contribute to 30–70% of acute respiratory infections. Identification of these respiratory viruses is not given high priority except influenza; however, the knowledge about prevalence of non-influenza viruses, their seasonal pattern and genetic evolution have significant epidemiological value. Methods As a part of National Influenza-like illness surveillance programme, respiratory specimens were collected children and adults with symptoms of ILI or ARI, between January 2012 and March 2015 (including SARI cases). Real-time PCR was done to identify 13 respiratory viruses. Sequencing was done for representative isolates of each virus using ABI 3730 Genetic Analyzer. Results During the study period between January 2012 and March 2015, a total of 648 patients with symptoms of ARI were included in this study. The mean age of the patients was 20.2 years (SD = 19.13, median = 18); 292 (45.1%) were children (≤13 years) and 356 (54.9%) were adults. Respiratory viruses were identified in 44% (287/648) of all patients. Influenza accounted for the maximum number of cases- 179/648 (27.6%). Among the non-influenza viruses, RSV predominated with 34 cases (5.2%), followed by HMPV 24 (3.7%) and PIV-3 20 (3%). Four patients died due to INF A/H1N1 as a result of acute respiratory distress syndrome (ARDS) (CFR 3.7%). Among the non-influenza viruses, no particular seasonality pattern was observed over the different months of the study period. Conclusion Antibiotic usage in treating acute respiratory infections empirically is not justified as nearly half of ARI are due to viruses; nearly 28% of them were due to influenza viruses. Among the non-influenza viruses, RSV predominated, followed by HMPV. This study is based on an active influenza surveillance initiated after 2009 pandemic influenza outbreak, in the Union territory of Puducherry which has contributed significantly to the knowledge of the burden of influenza and non-influenza viruses among children and adults. Such surveillance network has paved the way for better diagnosis and timely therapeutic interventions.

negative: New and emerging infectious diseases. New emerging infectious diseases include "severe acute respiratory distress syndrome" (SARS) and avian influenza A H5N1. First cases of SARS, induced by a new strain of coronavirus, were described in China in 2002 and by May 2003 8360 cases and 764 deaths were reported by the World Health Organization. The disease can be transmitted from person to person and at the onset is characterized by nonspecific symptoms such as a fever of > 38 degrees C, dry cough, myalgia, and dyspnea. Adults can develop severe hypoxemia requiring intubation, whereas the course of the disease is generally benign in children. Avian influenza A H5N1 is another emerging infectious disease transmitted from avian species to humans, without clear evidence of transmission from human to human. The widespread outbreaks of H5N1 avian influenza in 2003-2004 have caused major problems for the poultry industry in many Asian countries. On January 2004 the disease crossed over to humans, for the first time in Vietnam, causing 74 deaths to date (mortality rate of 50%) in southeastern countries. Unlike SARS, the avian flu occurs in rural areas, where people live in intimate contact with birds, and many of the victims are children < 5 years of age. As for SARS, the World Health Organization has adopted a global action plan to control avian influenza among chickens and ducks and at the same time to limit the threat of a human flu pandemic.

negative: Lack of association between genetic variants at ACE2 and TMPRSS2 genes involved in SARS-CoV-2 infection and human quantitative phenotypes Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptomes, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection uses the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as 58 medications in 36,339 volunteers from the Lifelines population biobank, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed a suggestive association of polymorphisms within the ACE2 gene with (1) the use of ARBs combination therapies (p=5.7x10-4), an association that is significantly stronger in females (pdiff=0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p=5.5x10-4). While these associations need to be confirmed in larger sample sizes, they suggest that these variants play a role in diseases such as hypertension and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.

negative: Antivirals for Respiratory Viral Infections: Problems and Prospects In the past two decades, several newly emerging and reemerging viral respiratory pathogens including several influenza viruses (avian influenza and pandemic influenza), severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV), have continued to challenge medical and public health systems. Thereafter, the development of cost-effective, broad-spectrum antiviral agents is the urgent mission of both virologists and pharmacologists. Current antiviral developments have focused targets on viral entry, replication, release, and intercellular pathways essential for viral life cycle. Here, we review the current literature on challenges and prospects in the development of these antivirals.

negative: Better influenza vaccines: an industry perspective Vaccination is the most effective measure at preventing influenza virus infections. However, current seasonal influenza vaccines are only protective against closely matched circulating strains. Even with extensive monitoring and annual reformulation our efforts remain one step behind the rapidly evolving virus, often resulting in mismatches and low vaccine effectiveness. Fortunately, many next-generation influenza vaccines are currently in development, utilizing an array of innovative techniques to shorten production time and increase the breadth of protection. This review summarizes the production methods of current vaccines, recent advances that have been made in influenza vaccine research, and highlights potential challenges that are yet to be overcome. Special emphasis is put on the potential role of glycoengineering in influenza vaccine development, and the advantages of removing the glycan shield on influenza surface antigens to increase vaccine immunogenicity. The potential for future development of these novel influenza vaccine candidates is discussed from an industry perspective.

negative: Using statistics and mathematical modelling to understand infectious disease outbreaks: COVID-19 as an example During an infectious disease outbreak, biases in the data and complexities of the underlying dynamics pose significant challenges in mathematically modelling the outbreak and designing policy. Motivated by the ongoing response to COVID-19, we provide a toolkit of statistical and mathematical models beyond the simple SIR-type differential equation models for analysing the early stages of an outbreak and assessing interventions. In particular, we focus on parameter estimation in the presence of known biases in the data, and the effect of non-pharmaceutical interventions in enclosed subpopulations, such as households and care homes. We illustrate these methods by applying them to the COVID-19 pandemic.

negative: Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment In the past two decades, the world has faced several infectious disease outbreaks. Ebola, Influenza A (H1N1), SARS, MERS, and Zika virus have had a massive global impact in terms of economic disruption, the strain on local and global public health. Most recently, the global outbreak of novel coronavirus 2019 (SARS-CoV-2) that causes COVID-19 is a newly discovered virus from the coronavirus family in Wuhan city, China, known to be a great threat to the public health systems. As of 15 April 2020, The Johns Hopkins University estimated that the COVID-19 affected more than two million people, resulting in a death toll above 130,000 around the world. Infected people in Europe and America correspond about 40% and 30% of the total reported cases respectively. At this moment only few Asian countries have controlled the disease, but a second wave of new infections is expected. Predicting inhibitor and target to the COVID-19 is an urgent need to protect human from the disease. Therefore, a protocol to identify anti-COVID-19 candidate based on computer-aided drug design is urgently needed. Thousands of compounds including approved drugs and drugs in the clinical trial are available in the literature. In practice, experimental techniques can measure the time and space average properties but they cannot be captured the structural variation of the COVID-19 during the interaction of inhibitor. Computer simulation is particularly suitable to complement experiments to elucidate conformational changes at the molecular level which are related to inhibition process of the COVID-19. Therefore, computational simulation is essential tool to elucidate the phenomenon. The structure-based virtual screening computational approach will be used to filter the best drugs from the literature, the investigate the structural variation of COVID-19 with the interaction of the best inhibitor is a fundamental step to design new drugs and vaccines which can combat the coronavirus. This mini-review will address novel coronavirus structure, mechanism of action, and trial test of antiviral drugs in the lab and patients with COVID-19.

negative: Recognizing COVID-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management Abstract Human coronavirus-associated myocarditis is known, and a number of COVID-19-related myocarditis cases have been reported. The pathophysiology of COVID-19-related myocarditis is thought to be a combination of direct viral injury and cardiac damage due to the host’s immune response. COVID-19 myocarditis diagnosis should be guided by insights from previous coronavirus and other myocarditis experience. The clinical findings include changes in ECG, cardiac biomarkers, and impaired cardiac function. When cardiac MRI is infeasible, cardiac CT angiography with delayed myocardial imaging may serve to exclude significant coronary artery disease and identify myocardial inflammatory patterns. Because many COVID-19 patients have cardiovascular comorbidities, myocardial infarction should be considered. Where the diagnosis remains uncertain, an endomyocardial biopsy may help identify active cardiac infection through viral genome amplification and possibly refine the treatment risks of systemic immunosuppression. Arrhythmias are not uncommon in the COVID-19 patients; however, its pathophysiology is still speculative. Nevertheless, clinicians should be vigilant to provide prompt monitoring and treatments. The long-term impact of COVID-19 myocarditis, including in the majority of mild cases remains unknown.

negative: The Seattle Flu Study: a multi-arm community-based prospective study protocol for assessing influenza prevalence, transmission, and genomic epidemiology Introduction. Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterize, and potentially contain new and emerging influenza strains at a population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population. Methods and Analysis. Starting in the 2018-19 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses, and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modeling platforms are in development to characterize the regional spread of influenza and other respiratory pathogens. Ethics and Dissemination. The study was approved by the University of Washington's Institutional Review Board. Results will be disseminated through talks at conferences, peer-reviewed publications, and on the study website (www.seattleflu.org).

negative: Informational needs assessment of non‐Hodgkin lymphoma survivors and their physicians

negative: Infectious bronchitis corona virus establishes productive infection in avian macrophages interfering with selected antimicrobial functions Infectious bronchitis virus (IBV) causes respiratory disease leading to loss of egg and meat production in chickens. Although it is known that macrophage numbers are elevated in the respiratory tract of IBV infected chickens, the role played by macrophages in IBV infection, particularly as a target cell for viral replication, is unknown. In this study, first, we investigated the ability of IBV to establish productive replication in macrophages in lungs and trachea in vivo and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using a double immunofluorescent technique, we observed that both IBV Massachusetts-type 41 (M41) and Connecticut A5968 (Conn A5968) strains replicate in avian macrophages at a low level in vivo. This in vivo observation was substantiated by demonstrating IBV antigens in macrophages following in vitro IBV infection. Further, IBV productive infection in macrophages was confirmed by demonstrating corona viral particles in macrophages and IBV ribonucleic acid (RNA) in culture supernatants. Evaluation of the functions of macrophages following infection of macrophages with IBV M41 and Conn A5968 strains revealed that the production of antimicrobial molecule, nitric oxide (NO) is inhibited. It was also noted that replication of IBV M41 and Conn A5968 strains in macrophages does not interfere with the induction of type 1 IFN activity by macrophages. In conclusion, both M41 and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting productive replications. During the replication of IBV in macrophages, their ability to produce NO can be affected without affecting the ability to induce type 1 IFN activity. Further studies are warranted to uncover the significance of macrophage infection of IBV in the pathogenesis of IBV infection in chickens.

negative: Reflections on Pandemic (H1N1) 2009 and the International Response Gabriel Leung and Angus Nicoll provide their reflections on the international response to the 2009 H1N1 influenza pandemic, including what went well and what changes need to be made in anticipation of future flu pandemics.

negative: Burden and seasonality of medically attended influenza like illness (ILI) in Ethiopia, 2012 to 2017 BACKGROUND: The influenza virus spreads rapidly around the world in seasonal epidemics, resulting in significant morbidity and mortality. Influenza-related incidence data are limited in many countries in Africa despite established sentinel surveillance. This study aimed to address the information gap by estimating the burden and seasonality of medically attended influenza like illness in Ethiopia. METHOD: Influenza sentinel surveillance data collected from 3 influenza like illness (ILI) and 5 Severe Acute Respiratory Illness (SARI) sites from 2012 to 2017 was used for analysis. Descriptive statistics were applied for simple analysis. The proportion of medically attended influenza positive cases and incidence rate of ILI was determined using total admitted patients and catchment area population. Seasonality was estimated based on weekly trend of ILI and predicted threshold was done by applying the “Moving Epidemic Method (MEM)”. RESULT: A total of 5715 medically attended influenza suspected patients who fulfills ILI and SARI case definition (77% ILI and 23% SARI) was enrolled. Laboratory confirmed influenza virus (influenza positive case) among ILI and SARI suspected case was 25% (1130/4426) and 3% (36/1289). Of which, 65% were influenza type A. The predominantly circulating influenza subtype were seasonal influenza A(H3N2) (n = 455, 60%) and Influenza A(H1N1)pdm09 (n = 293, 38.81%). The estimated mean annual influenza positive case proportion and ILI incidence rate was 160.04 and 52.48 per 100,000 population. The Incidence rate of ILI was higher in the age group of 15–44 years of age [‘Incidence rate (R) = 254.6 per 100,000 population’, 95% CI; 173.65, 335.55] and 5–14 years of age [R = 49.5, CI 95%; 31.47, 130.43]. The seasonality of influenza has two peak seasons; in a period from October–December and from April–June. CONCLUSION: Significant morbidity of influenza like illness was observed with two peak seasons of the year and seasonal influenza A (H3N2) remains the predominantly circulating influenza subtype. Further study need to be considered to identify potential risks and improving the surveillance system to continue early detection and monitoring of circulating influenza virus in the country has paramount importance.

negative: Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2–14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3–4 days without truncation and at 5–9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.

negative: Australian Quarantine Policy: From Centralization to Coordination with mid‐Pandemic COVID‐19 Shifts By combining a historical institutionalism approach with institutional isomorphism and punctuated equilibrium, this paper analyses quarantine policy change across 120 years of Australian quarantine history. By anchoring our analysis within specific time periods (years before the Spanish flu, seven decades of inaction, and multiple post‐1997 pandemic updates and responses), we highlight when and why policies did or did not change and how constant push‐and‐pulls between State and Commonwealth institutional ownership altered policy possibilities. The heart of our analysis showcases how Australia's successful COVID‐19 response is a unique output of prior quarantine policies, institutional evolution, and mid‐pandemic alterations of key national pandemic response plans. This article is protected by copyright. All rights reserved.

negative: Preparing to prevent severe acute respiratory syndrome and other respiratory infections Summary Globalisation and its effect on human development has rendered an environment that is conducive for the rapid international spread of severe acute respiratory syndrome (SARS), and other new infectious diseases yet to emerge. After the unprecedented multi-country outbreak of avian influenza with human cases in the winter of 2003–2004, an influenza pandemic is a current threat. A critical review of problems and solutions encountered during the 2003–2004 SARS epidemics will serve as the basis for considering national preparedness steps that can be taken to facilitate the early detection of avian influenza, and a rapid response to an influenza pandemic should it occur.

negative: Design and methods of a social network isolation study for reducing respiratory infection transmission: The eX-FLU cluster randomized trial Abstract Background Social networks are increasingly recognized as important points of intervention, yet relatively few intervention studies of respiratory infection transmission have utilized a network design. Here we describe the design, methods, and social network structure of a randomized intervention for isolating respiratory infection cases in a university setting over a 10-week period. Methodology/principal findings 590 students in six residence halls enrolled in the eX-FLU study during a chain-referral recruitment process from September 2012–January 2013. Of these, 262 joined as “seed” participants, who nominated their social contacts to join the study, of which 328 “nominees” enrolled. Participants were cluster-randomized by 117 residence halls. Participants were asked to respond to weekly surveys on health behaviors, social interactions, and influenza-like illness (ILI) symptoms. Participants were randomized to either a 3-Day dorm room isolation intervention or a control group (no isolation) upon illness onset. ILI cases reported on their isolation behavior during illness and provided throat and nasal swab specimens at onset, day-three, and day-six of illness. A subsample of individuals (N =103) participated in a sub-study using a novel smartphone application, iEpi, which collected sensor and contextually-dependent survey data on social interactions. Within the social network, participants were significantly positively assortative by intervention group, enrollment type, residence hall, iEpi participation, age, gender, race, and alcohol use (all P <0.002). Conclusions/significance We identified a feasible study design for testing the impact of isolation from social networks in a university setting. These data provide an unparalleled opportunity to address questions about isolation and infection transmission, as well as insights into social networks and behaviors among college-aged students. Several important lessons were learned over the course of this project, including feasible isolation durations, the need for extensive organizational efforts, as well as the need for specialized programmers and server space for managing survey and smartphone data.

negative: Factors associated with the willingness of health care personnel to work during an influenza public health emergency: an integrative review. INTRODUCTION The first decade of the 21st century has witnessed three major influenza public health emergencies: (1) the severe acute respiratory syndrome of 2002-2003; (2) the avian flu of 2006; and (3) the 2009 H1N1 pandemic influenza. An effective public health response to an influenza public health emergency depends on the majority of uninfected health care personnel (HCP) continuing to report to work. The purposes of this study were to determine the state of the evidence concerning the willingness of HCP to work during an influenza public health emergency, to identify the gaps for future investigation, and to facilitate evidence-based influenza public health emergency planning. METHODS A systemic literature review of relevant, peer-reviewed, quantitative, English language studies published from January 1, 2001 through June 30, 2010 was conducted. Search strategies included the Cochrane Library, PubMed, PubMed Central, EBSCO Psychological and Behavioral Sciences Collection, Google Scholar, ancestry searching of citations in relevant publications, and information from individuals with a known interest in the topic. RESULTS Thirty-two studies met the inclusion criteria. Factors associated with a willingness to work during an influenza public health emergency include: being male, being a doctor or nurse, working in a clinical or emergency department, working full-time, prior influenza education and training, prior experience working during an influenza emergency, the perception of value in response, the belief in duty, the availability of personal protective equipment (PPE), and confidence in one's employer. Factors found to be associated with less willingness were: being female, being in a supportive staff position, working part-time, the peak phase of the influenza emergency, concern for family and loved ones, and personal obligations. Interventions that resulted in the greatest increase in the HCP's willingness to work were preferential access to Tamiflu for the HCP and his/her family, and the provision of a vaccine for the individual and his/her family. CONCLUSIONS Understanding the factors that contribute to the willingness of HCP to report to work during an influenza public health emergency is critical to emergency planning and preparedness. Information from this review can guide emergency policy makers, planners, and implementers in both understanding and influencing the willingness of HCP to work during an influenza public health emergency.

negative: Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006) BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.

negative: COVID-19 and biologics for psoriasis: a high-epidemic area experience - Bergamo, Lombardy, Italy

negative: Chapter 12. Antiviral Agents Publisher Summary This chapter discusses the agents with activity primarily against RNA viruses. The communicable diseases of the respiratory tract are probably the most common cause of symptomatic human infections. The viruses that are causative agents for human respiratory disease comprise the five taxonomically distinct families: orthomyxoviridae, paramyxoviridae, picornaviridae, coronaviridae, and adenoviridae. The influenza viruses, which consist of types A, B, and C, belong to the family orthomyxoviridae. Types A and B have been associated with significant increases in mortality during epidemics. The disease may be asymptomatic or cause symptoms ranging from the common cold to fatal pneumonia. Immunization against influenza has been recommended for high-risk groups and antiviral chemotherapy (amantadine) is available for the treatment and prophylaxis of all influenza A infections. There is both a great need for and interest in developing a chemotherapeutic agent for the treatment of these two viral, respiratory tract pathogens. The family picornaviridae contains the genus Rhinovirus that is composed of over a hundred distinct serotypes. Amantadine and rimantadine are specifically active against influenza A virus infections. The amantadine recipients reported a higher incidence of side effects largely attributed to the central nervous system (CNS) symptoms. This difference in side effects may be a pharmacokinetic phenomenon that results in higher plasma concentrations of amantadine. Significant progress continues to be made in the clinical use and development of agents active against DNA viruses. Acyclovir (9-(2-h droxyethoxymethyl)guanine) has been the subject of several reviews and of a syrnposium. Considerable progress has been made in evaluating the clinical promise of acyclovir; however, there remains much to be learned concerning the best use of this drug in clinical practice. Significant strides have been made in the development of clinically useful antiviral agents, especially against the DNA viruses of the herpes family. Most of these agents are directed against viral nucleic acid synthesis and require activation by a virus-induced thymidine kinase. Researchers have begun to focus on other strategies that may produce broader spectrum anti-viral agents with different mechanisms of action.

negative: COVID-19 Patients with Recent Influenza A/B Infection: A Retrospective Study

negative: Clinical Profiles of Respiratory Syncytial Virus Subtypes A AND B Among Children Hospitalized with Bronchiolitis. In this analysis of a prospective, multicenter study of children hospitalized with bronchiolitis, 925 had respiratory syncytial virus (RSV)-A and 649 had RSV-B. Overall, bronchiolitis severity did not differ by RSV subtype. However, among children with RSV-only bronchiolitis, those children with RSV-A had higher risk of intensive care treatment (odds ratio, 1.31; 95% confidence interval, 1.00-1.71; P = 0.048) when compared with those having RSV-B.

negative: The COVID 19 novel coronavirus pandemic 2020: seaweeds to the rescue? Why does substantial, supporting research about the antiviral properties of seaweed polysaccharides seem to go unrecognized by the pharmaceutical community in these desperate times? Presently, there is lack of a vaccine that would lead to immunization against the virus COVID-19, but here are some of the characteristics that various seaweeds have and which may provide a glimpse into potential solutions of this global health problem in the near future and possibly forearm us for any future such pandemics. Many species of marine algae contain significant quantities of complex structural sulphated polysaccharides that have been shown to inhibit the replication of enveloped viruses. Other compounds, both of red algae (e.g., the lectin griffithsin and the phycocolloid carrageenan), and other sulphated polysaccharides extracted from green algae (i.e., ulvans) and brown algae (i.e., fucoidans) could be potential antiviral therapeutic agents against SARS-CoV-2.

negative: Rapid diagnostic testing for seasonal influenza: an evidence-based review and comparison with unaided clinical diagnosis. BACKGROUND Worldwide, seasonal influenza imposes a considerable health and economic burden. Clinical diagnosis of influenza-like illness (ILI) is complicated by non-specific symptomatology. Rapid flu tests (RFTs) impact treatment decisions and may improve patient care; yet, recommendations for RFT use are broad, and the performance of unaided clinical diagnosis relative to RFTs is unclear. OBJECTIVES To determine age-stratified, overall sensitivities and specificities of the widely studied RFT, QuickVue® (Quidel Corporation, San Diego, CA), and clinical diagnosis of ILI by meta-analysis and to seek factors associated with poorer clinical diagnostic discrimination. METHODS A systematic literature review was conducted using article selection criteria identifying studies indexed in PubMed/MEDLINE, the Cochrane Library, and other pertinent sources of studies reporting sensitivity, specificity, and effects of RFTs and clinical diagnosis on decision-making for patients with ILI. RESULTS QuickVue's® diagnostic specificity exceeds that of unaided clinical diagnosis by 29-31%. False-positive results occur approximately 8.2 times more frequently by unaided clinical diagnosis than by the RFT alone. These findings were unaffected by seasonal variations in disease prevalence. RFTs reduce diagnostic testing, antibiotic use, and emergency department utilization while increasing antiviral prescription rates. No systematic relationship between the broadness of clinical diagnostic criteria for influenza and diagnostic performance was observed across studies included in this review. CONCLUSIONS Use of RFTs improves seasonal influenza diagnostic specificity above that based on unaided clinical diagnosis irrespective of the broadness of clinical diagnostic criteria, and affects clinical decision-making. These results provide an improved framework upon which to diagnose influenza, design future RFT studies, and modify existing recommendations for improved ILI patient management.

negative: Influenza Vaccination in Type 2 Diabetes Patients: Coverage Status and Its Determinants in Southwestern Saudi Arabia Despite the significant role of seasonal influenza vaccination in preventing and minimizing the serious complications of influenza infection in type 2 diabetes mellitus (T2DM) patients, unsatisfactory compliance still exists for vaccination. Study objectives were to explore the vaccination status and determinants in T2DM patients in southwestern Saudi Arabia. A cross-sectional study on a representative sample of T2DM patients in Abha city, southwestern Saudi Arabia, was conducted. Data for sociodemographic characteristics, clinical criteria, vaccination status, vaccination motivators and barriers and seasonal influenza knowledge were collected. Out of 353 T2DM patients included in the study, seasonal influenza vaccination coverage was 61% in year 2017. A significant factors associated with non-vaccination were; poor influenza and its vaccine knowledge (OR = 4.31, 95% CI: 2.73–6.80), illiteracy (OR = 1.93, 95% CI: 1.11–3.37), and more than 10 years disease duration (OR = 2.07, 95% CI: 1.11–3.87). Presence of family history of DM and ischemic heart comorbidity minimized the possibility of non-vaccination (OR = 0.54 and 0.28 respectively). Healthcare givers’ advice was the most reported vaccination motivator (84.7%) while; fear of vaccine side effects was the most stated barrier (73%). In conclusion, influenza vaccination rate among T2DM in the present study is less than the recommended level. Continuous primary health care center-based educational programs should be implemented to aware and encourage influenza vaccination among T2DM patients.

negative: Temporal rise in the proportion of both younger adults and older adolescents among COVID-19 cases in Germany: evidence of lesser adherence to social distancing practices? BACKGROUND: There is uncertainty about the role of different age groups in propagating the SARS-CoV-2 epidemics in different countries, particularly under current social distancing practices. METHODS: We used the Robert Koch Institute data on weekly COVID-19 cases in different age groups in Germany. To minimize the effect of changes in healthcare seeking behavior (e.g. for older adults) and testing practices, we included the following eight 5-year age groups in the analyses: 10–14y through 45–49y. For each age group g, we considered the proportion PL(g) of individuals in age group g among all detected cases aged 10–49y during weeks 13–14, 2020 (later period), as well as corresponding proportion PE(g) for weeks 10–11, 2020 (early period), and defined the relative risk RR(g) for the age group g to be the ratio RR(g) = PL(g)/PE(g). For each pair of age groups g1, g2, a higher value of RR(g1) compared to RR(g2), or, alternatively, a value above 1 for the odds ratio OR(g1, g2) = RR(g1)/RR(g2) for a COVID-19 case to be in group g1 vs. g2 for the later vs. early periods is interpreted as the relative increase in the population incidence of SARS-Cov-2 in the age group g1 compared to g2 for the later vs. early period. RESULTS: The relative risk RR(g) was highest for individuals aged 20–24y (RR=1.4(95% CI (1.27,1.55))), followed by individuals aged 15–19y (RR=1.14(0.99,1.32)), aged 30–34y (RR=1.07(0.99,1.16)), aged 25–29y (RR= 1.06(0.98,1.15)), aged 35–39y (RR=0.95(0.87,1.03)), aged 40–44y (RR=0.9(0.83,0.98)), aged 45–49y (RR=0.83(0.77,0.89)) and aged 10–14y (RR=0.78(0.64,0.95)). For the age group 20–24y, the odds ratio relative to any other age group for a case to be during the later vs. early period was significantly above 1. For the age group 15–19y, the odds ratio relative to any other age group either above 35y or 10–14y for a case to be during the later vs. early period was significantly above 1. CONCLUSIONS: The observed relative increase with time in the prevalence of individuals aged 15–34y (particularly those aged 20–24y) among detected COVID-19 cases in Germany is unlikely to be explained by increases in the likelihood of seeking medical care or the likelihood of being tested for individuals in those age groups compared to individuals aged 35–49y or 10–14y, and should be indicative of the actual increase in the prevalence of individuals aged 15–34y among SARS-CoV-2 infections in the German population. That increase likely reflects elevated mixing among individuals aged 15–34y (particularly those aged 20–24y) compared to other age groups, possibly due to lesser adherence to social distancing practices.

negative: A year of terror and a century of reflection: perspectives on the great influenza pandemic of 1918–1919 BACKGROUND: In the spring of 1918, the “War to End All Wars”, which would ultimately claim more than 37 million lives, had entered into its final year and would change the global political and economic landscape forever. At the same time, a new global threat was emerging and would become one of the most devastating global health crises in recorded history. MAIN TEXT: The 1918 H1N1 pandemic virus spread across Europe, North America, and Asia over a 12-month period resulting in an estimated 500 million infections and 50–100 million deaths worldwide, of which ~ 50% of these occurred within the fall of 1918 (Emerg Infect Dis 12:15-22, 2006, Bull Hist Med 76:105-115, 2002). However, the molecular factors that contributed to the emergence of, and subsequent public health catastrophe associated with, the 1918 pandemic virus remained largely unknown until 2005, when the characterization of the reconstructed pandemic virus was announced heralding a new era of advanced molecular investigations (Science 310:77-80, 2005). In the century following the emergence of the 1918 pandemic virus we have landed on the Moon, developed the electronic computer (and a global internet), and have eradicated smallpox. In contrast, we have a largely remedial knowledge and understanding of one of the greatest scourges in recorded history. CONCLUSION: Here, we reflect on the 1918 influenza pandemic, including its emergence and subsequent rapid global spread. In addition, we discuss the pathophysiology associated with the 1918 virus and its predilection for the young and healthy, the rise of influenza therapeutic research following the pandemic, and, finally, our level of preparedness for future pandemics.

negative: Evaluation of custom multiplex real - time RT - PCR in comparison to fast - track diagnostics respiratory 21 pathogens kit for detection of multiple respiratory viruses BACKGROUND: Severe acute respiratory infections in children can be fatal, rapid identification of the causative agent and timely treatment can be life saving. Multiplex real time RT-PCR helps in simultaneous detection of multiple viruses saving cost, time and labour. Commercially available multiplex real time RT-PCR kits are very expensive. Therefore the aim of the present study was to develop a cost effective multiplex real time RT-PCR for the detection of 18 respiratory viruses and compare it with an in-vitro diagnostics approved Fast Track Diagnostic Respiratory Pathogens 21 Kit (FTD). METHODS: Nasopharyngeal aspirates and throat swabs were collected and processed for extraction of nucleic acid using an automated extraction system and multiplex real time RT-PCR was performed using the FTD kit and a custom assay on 356 samples. RESULTS: Custom and FTD assays detected one or more respiratory viruses in 268 (75.29 %) and 262 (73.60 %) samples respectively. The concordance between the custom assay and the FTD assay was 100 % for HCoV OC43, HCoV 229E, HPIV-1, HPIV-2, HBoV, HPeV, Flu A, and Influenza A(H1N1)pdm09 and 94.66 – 99.71 % for the remaining viruses; Flu B (99.71 %), HRV (99.71 %), HPIV-3 (98.87 %), HPIV-4 (99.43 %), HCoV NL63 (99.71 %), HMPV A/B (99.71 %), RSV A/B (94.66 %), EV (98.31 %), HCoV HKU1 (99.71 %), HAdV (99.71 %). Major discrepancy was observed for RSV A/B, which was over detected in 18 samples by the custom assay as compared to the FTD assay. The custom assay was much cheaper than the FTD assay and the time taken was only 29 min more. CONCLUSION: The custom primer and probe mix was found to be comparable to the FTD assay with good concordance but was much cheaper and the time taken for reporting was only 29 min more. The low cost custom multiplex RT-PCR can be a useful alternative to the costly FTD kit for rapid identification of viral aetiology in resource limited settings.

negative: Comparative Analysis of Early-Stage Clinical Features Between COVID-19 and Influenza A H1N1 Virus Pneumonia Introduction: Influenza virus pneumonia and COVID-19 are two different types of respiratory viral pneumonia but with very similar clinical manifestations. The aim of the present study was to help clinicians gain a better understanding about differences between Influenza virus pneumonia and COVID-19 by comparative analysis of the early-stage clinical features. Methods: Clinical data of patients with confirmed diagnosis of COVID-19 and influenza A pneumonia identified in our hospital were collected and analyzed retrospectively to identify the clinical features that could differentiate between the two types of viral pneumonia. Results: The two types of viral pneumonia mainly affected adults, especially people over 50 years, with no gender difference between them. Fever, cough, sputum and muscle soreness were the most common symptoms of COVID-19. Some patients with COVID-19 may also exhibit digestive tract symptoms. Elevation of C-reactive protein (CRP) was a more common phenomenon in patients with COVID-19 than that in patients with influenza A H1N1 virus pneumonia. In addition, eosinophil count was decreased and the monocyte percentage was increased in COVID-19 patients. The grid-form shadow was a typical presentation of COVID-19 on the lung CT image, and the disease usually progressed quickly within a week. Conclusion: Influenza pneumonia and COVID-19 are two different types of respiratory viral pneumonia with very similar clinical manifestations. The percentage of monocytes is increased and the eosinophil count is decreased in COVID-19. Glass-ground density exudation shadow located peripherally is the typical sign of COVID-19 on the lung CT image, and the shadow often with grid-form sign. These features may not be typically observed in patients with influenza pneumonia. Chest CT scan combined with nucleic acid detection is an effective and accurate method for diagnosing COVID-19. Blood routine test has a limited diagnostic value in differentiating the two forms of pneumonia.

negative: The SARS-CoV-2 outbreak: What we know Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.

negative: The dark cloud with a silver lining: Assessing the impact of the SARS COVID-19 pandemic on the global environment Abstract The Severe Acute Respiratory Syndrome-Coronavirus Disease 2019 (COVID-19) pandemic caused by a novel coronavirus known as SARS-CoV-2 has caused tremendous suffering and huge economic losses. We hypothesized that extreme measures of partial-to-total shutdown might have influenced the quality of the global environment because of decreased emissions of atmospheric pollutants. We tested this hypothesis using satellite imagery, climatic datasets (temperature, and absolute humidity), and COVID-19 cases available in the public domain. While the majority of the cases were recorded from Western countries, where mortality rates were strongly positively correlated with age, the number of cases in tropical regions was relatively lower than European and North American regions, possibly attributed to faster human-to-human transmission. There was a substantial reduction in the level of nitrogen dioxide (NO2: 0.00002 mol m−2), a low reduction in CO (<0.03 mol m−2), and a low-to-moderate reduction in Aerosol Optical Depth (AOD: ~0.1–0.2) in the major hotspots of COVID-19 outbreak during February–March 2020, which may be attributed to the mass lockdowns. Our study projects an increasing coverage of high COVID-19 hazard at absolute humidity levels ranging from 4 to 9 g m−3 across a large part of the globe during April–July 2020 due to a high prospective meteorological suitability for COVID-19 spread. Our findings suggest that there is ample scope for restoring the global environment from the ill-effects of anthropogenic activities through temporary shutdown measures.

negative: Weather: driving force behind the transmission of severe acute respiratory syndrome in China? Background: The association between weather and severe acute respiratory syndrome (SARS) transmission in Beijing and Hong Kong in the 2003 epidemic was studied to examine the effect of weather on SARS transmission. Methods: Pearson’s correlation analyses and negative binomial regression analyses were used to quantify the correlations between the daily newly reported number of SARS cases and weather variables, using daily disease notification data and meteorological data from the two locations. Results: The results indicate that there were inverse association between the number of daily cases and maximum and/or minimum temperatures whereas air pressure was found to be positively associated with SARS transmission. Conclusion: The study suggests that weather might be a contributory factor in the 2003 SARS epidemic, in particular in the transmission among the community members.

negative: Generalized SHAP: Generating multiple types of explanations in machine learning Many important questions about a model cannot be answered just by explaining how much each feature contributes to its output. To answer a broader set of questions, we generalize a popular, mathematically well-grounded explanation technique, Shapley Additive Explanations (SHAP). Our new method - Generalized Shapley Additive Explanations (G-SHAP) - produces many additional types of explanations, including: 1) General classification explanations; Why is this sample more likely to belong to one class rather than another? 2) Intergroup differences; Why do our model's predictions differ between groups of observations? 3) Model failure; Why does our model perform poorly on a given sample? We formally define these types of explanations and illustrate their practical use on real data.

negative: Low mortality rates related to respiratory virus infections after bone marrow transplantation Respiratory viruses (RVs) frequently cause severe respiratory disease in bone marrrow transplant (BMT) recipients. To evaluate the frequency of RV, nasal washes were collected year-round from BMT recipients with symptoms of upper respiratory tract infection (URI). Direct immunofluorescence assay was performed for respiratory syncytial virus (RSV), influenza (Flu) A and B, adenovirus and parainfluenza (Paraflu) virus. Patients with RSV pneumonia or with upper RSV infection, but considered at high risk for developing RSV pneumonia received aerosolized ribavirin. Oseltamivir was given to patients with influenza. A total of 179 patients had 392 episodes of URI. In all, 68 (38%) tested positive: RSV was detected in 18 patients (26.4%), Flu B in 17 (25%), Flu A in 11 (16.2%) and Paraflu in 7 (10.3%). A total of 14 patients (20.6%) had multiple RV infections or coinfection. RSV pneumonia developed in 55.5% of the patients with RSV-URI. One of the 15 patients (6.6%) with RSV pneumonia died. Influenza pneumonia was diagnosed in three patients (7.3%). RSV and influenza infections peaked in fall–winter and winter–spring months, respectively. We observed decreased rates of influenza and parainfluenza pneumonia and low mortality because of RSV pneumonia. The role of antiviral interventions such as aerosolized ribavirin and new neuraminidase inhibitors remains to be defined in randomized trials.

negative: Allergic respiratory disease care in the COVID-19 era: a EUFOREA statement Abstract Spring and Summer 2020 are unique in that the challenges of care for those suffering from pollen allergy coincide with the COVID-19 pandemic. Several considerations are important to allow optimal care of allergic rhinitis (AR) and asthma and hence prevention of coronavirus spread through sneezing, rhinorrhoea and coughing. This compact overview of recommendations by the EUFOREA expert teams on allergic airway diseases and AIT is based on investigation of the current COVID-19 literature in association with the key words above and shared clinical experience of the experts involved. It deals with similarities and differences between AR and coronavirus infection, specific recommendations for allergic disease care in the COVID-19 era, including guidance on allergen specific immunotherapy, AIT.

negative: A Case Series of Patients Coinfected With Influenza and COVID-19 Coronavirus disease 2019, also called COVID-19, is a global pandemic resulting in significant morbidity and mortality worldwide. In the United States, influenza infection occurs mainly during winter and several factors influence the burden of the disease, including circulating virus characteristics, vaccine effectiveness that season, and the duration of the season. We present a case series of 3 patients with coinfection of COVID-19 and influenza, with 2 of them treated successfully and discharged home. We reviewed the literature of patients coinfected with both viruses and discussed the characteristics, as well as treatment options.

negative: 100 years of influenza research seen through the lens of Covid-19

negative: Detecting influenza and emerging avian influenza virus by influenza and pneumonia surveillance systems in a large city in China, 2005 to 2016 BACKGROUND: Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease. METHODS: The HIS (hospital information system) modified influenza surveillance system (ISS) and a newly built pneumonia surveillance system (PSS) were used to monitor the influenza viruses in Changsha City, China. The ISS was used to monitor outpatients in two sentinel hospitals and to detect mild influenza and avian influenza cases, and PSS was used to monitor inpatients in 49 hospitals and to detect severe and death influenza cases. RESULTS: From 2005 to 2016, there were 3,551,917 outpatients monitored by the ISS system, among whom 126,076 were influenza-like illness (ILI) cases, with the ILI proportion (ILI%) of 3.55%. After the HIS was used, the reported incident cases of ILI and ILI% were increased significantly. From March, 2009 to September, 2016, there were 5,491,560 inpatient cases monitored by the PSS system, among which 362,743 were pneumonia cases, with a proportion of 6.61%. Among pneumonia cases, about 10.55% (38,260/362,743) of cases were severe or death cases. The pneumonia incidence increased each year in the city. Among 15 avian influenza cases reported from January, 2005 to September, 2016, there were 26.7% (4/15) mild cases detected by the HIS-modified ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available. CONCLUSIONS: The HIS was able to improve the efficiency of the ISS for monitoring ILI and emerging avian influenza virus. However, the efficiency of the system needs to be verified in a wider area for a longer time span in China.

negative: Within-mother analysis of seasonal patterns in health at birth. A large literature describes relationships between month of birth, birth weight, and gestation. These relationships are hypothesized to reflect the causal impact of seasonal environmental factors. However, recent work casts doubt on this interpretation by showing that mothers with lower socioeconomic status are more likely to give birth in months that are associated with poorer birth outcomes. Seasonality in the numbers of conceptions in different months can also induce a mechanical correlation between preterm birth and month of birth. This paper analyzes the seasonality of health at birth using a large sample of 647,050 groups of US siblings representing 1,435,213 children. By following the same mother over time, we eliminate differences in fixed maternal characteristics as an explanation for seasonal differences in health at birth. We find a sharp trough in gestation length among babies conceived in May, which corresponds to an increase in prematurity of more than 10%. Birth weight conditional on gestation length, however, is found to be strongly hump-shaped over the year, with 8-9 additional g for summer conceptions. We examine several potential mechanisms for explaining seasonality in birth outcomes that have generally been dismissed in the literature on seasonality in rich countries, notably disease prevalence and nutrition. The May trough in gestation length coincides with a higher influenza prevalence in January and February, when these babies are nearing full term, whereas the hump shape in birth weight is associated with a similar pattern in pregnancy weight gain.

negative: Epidemic psychiatry: The opportunities and challenges of COVID-19

negative: Circulation of other respiratory viruses and viral co-infection during the 2009 pandemic influenza Abstract Coinciding with the pandemic wave of the influenza A(H1N1)pdm09 virus, other respiratory viruses have co-circulated in our area and were responsible for many acute respiratory infections and influenza-like illness (ILI). Apart from the pandemic virus that was responsible for most ILI cases, incidence rates of other viruses have varied among geographical areas. In general, human rhinovirus was the most frequent among individuals from the community, and respiratory syncytial virus among hospitalized patients. Detection rates of other respiratory viruses such as human metapneumovirus, adenovirus or parainfluenza viruses have been much lower. On the basis of an interference mechanism, human rhinovirus may contribute to modulate the pandemic wave, although available data are not conclusive to support this hypothesis. In contrast, the epidemic wave of respiratory syncytial virus during 2009–2010 was similar to previous seasons. Overall, incidence rates of respiratory viruses other than influenza did not change significantly during the pandemic season compared to other seasons. No association has been found between coinfection of pandemic influenza and other respiratory viruses with the prognosis of patients with influenza. The involvement of clinical virology laboratories in the etiological diagnosis of ILI cases has improved and has optimized diagnostic procedures.

negative: COVID-19 outbreak: Migration, effects on society, global environment and prevention Abstract The COVID-19 pandemic is considered as the most crucial global health calamity of the century and the greatest challenge that the humankind faced since the 2nd World War. In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China and was named by the World Health Organization as COVID-19 (coronavirus disease 2019). A new class of corona virus, known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been found to be responsible for occurrence of this disease. As far as the history of human civilization is concerned there are instances of severe outbreaks of diseases caused by a number of viruses. According to the report of the World Health Organization (WHO as of April 18 2020), the current outbreak of COVID-19, has affected over 2164111 people and killed more than 146,198 people in more than 200 countries throughout the world. Till now there is no report of any clinically approved antiviral drugs or vaccines that are effective against COVID-19. It has rapidly spread around the world, posing enormous health, economic, environmental and social challenges to the entire human population. The coronavirus outbreak is severely disrupting the global economy. Almost all the nations are struggling to slow down the transmission of the disease by testing & treating patients, quarantining suspected persons through contact tracing, restricting large gatherings, maintaining complete or partial lock down etc. This paper describes the impact of COVID-19 on society and global environment, and the possible ways in which the disease can be controlled has also been discussed therein.

negative: Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85–95%, and four 30–50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R(0) values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.

negative: Estimating Incidence Curves of Several Infections Using Symptom Surveillance Data We introduce a method for estimating incidence curves of several co-circulating infectious pathogens, where each infection has its own probabilities of particular symptom profiles. Our deconvolution method utilizes weekly surveillance data on symptoms from a defined population as well as additional data on symptoms from a sample of virologically confirmed infectious episodes. We illustrate this method by numerical simulations and by using data from a survey conducted on the University of Michigan campus. Last, we describe the data needs to make such estimates accurate.

negative: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.

negative: Examining the relationship between infectious diseases and flooding in Europe: A systematic literature review and summary of possible public health interventions Introduction Many infectious diseases are sensitive to climatic changes; specifically, flooding. This systematic literature review aimed to strengthen the quality and completeness of evidence on infectious diseases following flooding, relevant to Europe. Methods A systematic literature review from 2004–2012 was performed. Focused searches of the following databases were conducted: Medline, Scopus, PubMed, Cochrane Library, and Evidence Aid. Personal communications with key informants were also reviewed. Results Thirty-eight studies met the inclusion criteria. Evidence suggested that water-borne, rodent-borne, and vector-borne diseases have been associated with flooding in Europe, although at a lower incidence than developing countries. Conclusion Disease surveillance and early warning systems, coupled with effective prevention and response capabilities, can reduce current and future vulnerability to infectious diseases following flooding.

negative: Determinants of refusal of A/H1N1 pandemic vaccination in a high risk population: a qualitative approach. BACKGROUND Our study analyses the main determinants of refusal or acceptance of the 2009 A/H1N1 vaccine in patients with cystic fibrosis, a high-risk population for severe flu infection, usually very compliant for seasonal flu vaccine. METHODOLOGY/PRINCIPAL FINDINGS We conducted a qualitative study based on semi-structured interviews in 3 cystic fibrosis referral centres in Paris, France. The study included 42 patients with cystic fibrosis: 24 who refused the vaccine and 18 who were vaccinated. The two groups differed quite substantially in their perceptions of vaccine- and disease-related risks. Those who refused the vaccine were motivated mainly by the fears it aroused and did not explicitly consider the 2009 A/H1N1 flu a potentially severe disease. People who were vaccinated explained their choice, first and foremost, as intended to prevent the flu's potential consequences on respiratory cystic fibrosis disease. Moreover, they considered vaccination to be an indirect collective prevention tool. Patients who refused the vaccine mentioned multiple, contradictory information sources and did not appear to consider the recommendation of their local health care provider as predominant. On the contrary, those who were vaccinated stated that they had based their decision solely on the clear and unequivocal advice of their health care provider. CONCLUSIONS/SIGNIFICANCE These results of our survey led us to formulate three main recommendations for improving adhesion to new pandemic vaccines. (1) it appears necessary to reinforce patient education about the disease and its specific risks, but also general population information about community immunity. (2) it is essential to disseminate a clear and effective message about the safety of novel vaccines. (3) this message should be conveyed by local health care providers, who should be involved in implementing immunization.

negative: Higher virulence of swine H1N2 influenza viruses containing avian-origin HA and 2009 pandemic PA and NP in pigs and mice Pigs are capable of harbouring influenza A viruses of human and avian origin in their respiratory tracts and thus act as an important intermediary host to generate novel influenza viruses with pandemic potential by genetic reassortment between the two viruses. Here, we show that two distinct H1N2 swine influenza viruses contain avian-like or classical swine-like hemagglutinins with polymerase acidic (PA) and nucleoprotein (NP) genes from 2009 pandemic H1N1 influenza viruses that were found to be circulating in Korean pigs in 2018. Swine H1N2 influenza virus containing an avian-like hemagglutinin gene had enhanced pathogenicity, causing severe interstitial pneumonia in infected pigs and mice. The mortality rate of mice infected with swine H1N2 influenza virus containing an avian-like hemagglutinin gene was higher by 100% when compared to that of mice infected with swine H1N2 influenza virus harbouring classical swine-like hemagglutinin. Further, chemokines attracting inflammatory cells were strongly induced in lung tissues of pigs and mice infected by swine H1N2 influenza virus containing an avian-like hemagglutinin gene. In conclusion, it is necessary for the well-being of humans and pigs to closely monitor swine influenza viruses containing avian-like hemagglutinin with PA and NP genes from 2009 pandemic H1N1 influenza viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04572-z) contains supplementary material, which is available to authorized users.

negative: Assessing the impacts of mutations to the structure of COVID-19 spike protein via sequential Monte Carlo Proteins play a key role in facilitating the infectiousness of the 2019 novel coronavirus. A specific spike protein enables this virus to bind to human cells, and a thorough understanding of its 3-dimensional structure is therefore critical for developing effective therapeutic interventions. However, its structure may continue to evolve over time as a result of mutations. In this paper, we use a data science perspective to study the potential structural impacts due to ongoing mutations in its amino acid sequence. To do so, we identify a key segment of the protein and apply a sequential Monte Carlo sampling method to detect possible changes to the space of low-energy conformations for different amino acid sequences. Such computational approaches can further our understanding of this protein structure and complement laboratory efforts.

negative: Analysis of meteorological conditions and prediction of epidemic trend of 2019-nCoV infection in 2020 Objective: To investigate the meteorological condition for incidence and spread of 2019-nCoV infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease. Methods: The meteorological factors during the outbreak period of the novel coronavirus pneumonia in Wuhan in 2019 were collected and analyzed, and were confirmed with those of Severe Acute Respiratory Syndrome (SARS) in China in 2003. Data of patients infected with 2019-nCoV and SARS coronavirus were collected from WHO website and other public sources. Results: This study found that the suitable temperature range for 2019-nCoV coronavirus survival is (13-24 degree Celsius), among which 19 degree Celsius lasting about 60 days is conducive to the spread between the vector and humans; the humidity range is 50%-80%, of which about 75% humidity is conducive to the survival of the coronavirus; the suitable precipitation range is below 30 mm/ month. Cold air and continuous low temperature over one week are helpful for the elimination of the virus. The prediction results show that with the approach of spring, the temperature in north China gradually rises, and the coronavirus spreads to middle and high latitudes along the temperature line of 13-18 degree Celsius. The population of new coronavirus infections is concentrated in Beijing, Tianjin, Hebei, Jiangsu, Zhejiang, Shanghai and other urban agglomerations. Starting from May 2020, the Beijing-Tianjin-Hebei urban agglomeration, the Central China Zhengzhou-Wuhan urban agglomeration, the eastern Jiangsu-Zhejiang-Shanghai urban agglomeration, and the southern Pearl River Delta urban agglomeration are all under a high temperature above 24 degree Celsius, which is not conducive to the survival and reproduction of coronaviruses, so the epidemic is expected to end. Conclusions: A wide range of continuous warm and dry weather is conducive to the survival of 2019-nCoV. The coming of spring, in addition to the original Wuhan-Zhengzhou urban agglomeration in central China, means that the prevention and control measures in big cities located in mid-latitude should be strengthened, especially the monitoring of transportation hubs. The Pearl River Delta urban agglomeration is a concentrated area of population in south China, with a faster temperature rise than those in mid-high latitudes, and thus the prevention in this area should be prioritized. From a global perspective, cities with a mean temperature below 24 degree Celsius are all high-risk cities for 2019-nCoV transmission before June.

negative: Health and Demographic Impact on COVID-19 Infection and Mortality in US Counties Introduction With the pandemic of COVID-19, the number of confirmed cases and related deaths are increasing in the US. We aimed to understand the potential impact of health and demographic factors on the infection and mortality rates of COVID-19 at the population level. Methods We collected total number of confirmed cases and deaths related to COVID-19 at the county level in the US from January 21, 2020 to April 23, 2020. We extracted health and demographic measures for each US county. Multivariable linear mixed effects models were used to investigate potential correlations of health and demographic characteristics with the infection and mortality rates of COVID-19 in US counties. Results Our models showed that several health and demographic factors were positively correlated with the infection rate of COVID-19, such as low education level and percentage of Black. In contrast, several factors, including percentage of smokers and percentage of food insecure, were negatively correlated with the infection rate of COVID-19. While the number of days since first confirmed case and the infection rate of COVID-19 were negatively correlated with the mortality rate of COVID-19, percentage of elders (65 and above) and percentage of rural were positively correlated with the mortality rate of COVID-19. Conclusions At the population level, health and demographic factors could impact the infection and mortality rates of COVID-19 in US counties.

negative: New Epidemiological and Clinical Signatures of 18 Pathogens from Respiratory Tract Infections Based on a 5-Year Study BACKGROUND: Respiratory tract infections (RTIs) are a heavy burden on society. However, due to the complex etiology of RTIs, the clinical diagnosis, treatment, and prevention of these infections remain challenging, especially in developing countries. METHODS: To determine the epidemiological and clinical characteristics of 18 respiratory pathogens, we analyzed 12,502 patients with acute respiratory infections (ARIs) by performing polymerase chain reaction (PCR) on patient pharyngeal swabs. RESULTS: Samples positive for at least 1 pathogen were obtained from 48.42% of the total patients. Of these pathogen-positive patients, 17.99% were infected with more than 1 pathogen. Of the 18 pathogens analyzed, four were detected with a positive detection rate (PDR) > 5%: influenza A virus (IAV) > respiratory syncytial virus (RSV) >Mycoplasma pneumoniae (MP) > human coronavirus (HCoV). The pathogens with the 4 highest co-infection rates (CIRs) were as follows: HCoV > human bocavirus (HBoV) > enterovirus (EV) > parainfluenza virus (PIV). The overall positive detection rate (PDR) varied significantly according to patient age, the season and year of detection, and the disease subgroup, but not according to patient sex. The individual PDRs of the pathogens followed 3 types of distributions for patient sex, 4 types of distributions for patient age, 4 types of seasonal distributions, 2 types of seasonal epidemic trends, 4 types of yearly epidemic trends, and different susceptibility distributions in the disease subgroups. Additionally, the overall CIR showed significantly different distributions according to patient sex, patient age, and the disease subgroup, whereas the CIRs of individual pathogens suggested significant preference characteristics. CONCLUSION: IAV remains the most common pathogen among the pathogens analyzed. More effort should be directed toward the prevention and control of pathogens that show a trend of increasing incidence such as HCoV, human adenovirus (ADV), and RSV. Although clinically distinguishing specific pathogens responsible for RTIs is difficult, the epidemiological and clinical characteristics of the various RTI-causing agents could provide clues for clinicians, thereby informing decisions regarding prevention and medication and guiding appropriate public health strategies.

negative: Effect of genomic drift of influenza PCR tests Abstract Background Nucleic acid amplification assays have become the method of choice for influenza (Flu) testing due to superior accuracy and faster turnaround time. Although assays are designed to detect highly conserved genomic targets, mutations can influence test sensitivity. Most of the circulating viruses in the United States during the 2014–2015 season were associated with significant genetic drift; however, the effect on testing was unknown. Objectives and study design We compared the performance of Prodesse ProFlu+/ProFAST+ (PFlu/PFAST), FilmArray Respiratory Panel (RP), cobas® Influenza A/B test (cIAB), and Xpert® Flu (Xpt) in a retrospective analysis of consecutive nasopharyngeal specimens received for a two-week period during the winter of 2015. Furthermore, limits of detection (LOD) were determined with six isolates of Flu. Results Of the 275 specimens, 63 were positive for FluA by PFAST, 60 were positive by RP, 58 were positive by cIAB and 52 were positive by Xpt. Only a subset of 135 specimens was tested by PFlu, of which 32 were positive. The sensitivity/specificity for PFAST, RP, cIAB, Xpt and PFlu was 100/99.1%, 96.7/99.5%, 91.8/99.1%, 85.2%/100%, and 75.6%/98.9%, respectively. LOD analyses demonstrated assay performance variations were strain associated. Specifically, PFlu’s and cIAB’s LODs were higher with A/Texas/50/2012-like and A/Switzerland/9715293/2013-like strains, while Xpt’s highest LOD was with the Swiss strain. Conclusions Strain-associated assay performance variation is known to occur with other Flu test methods; hence, it is not surprising that such variation would be observed with molecular tests. Careful monitoring and reporting for strain-associated variances are warranted for all test methods.

negative: Detection of avian influenza virus and newcastle disease virus by duplex one step RT PCR Newcastle disease Virus (NDV), a member of the Paramyxoviridae family, and Influenza virus, from the Orthomyxoviridae family, are two main avian pathogens that cause serious economic problems in poultry farming. NDV strains are classified into three major pathotypes: velogenic, mesogenic, and lentogenic. Avian influenza viruses (AIV) are also divided into: low pathogenic (LPAI) and highly pathogenic (HPAI) strains. Both viruses are enveloped, single stranded, negative-sense RNA viruses which give similar symptoms ranging from sub-clinical infections to severe disease, including loss in egg production, acute respiratory syndrome, and high mortality, depending on their level of pathogenicity. This similarity hinders diagnosis when based solely on clinical and post mortem examination. Most of the currently available molecular detection methods are also pathogenspecific, so that more than one RT-PCR is then required to confirm or exclude the presence of both pathogens. To overcome this disadvantage, we have applied a One Step Duplex RT-PCR method to distinguish between those two pathogens. The main objective of the project was to develop a universal, fast, and inexpensive method which could be used in any veterinary laboratory.

negative: Self-reported anticipated compliance with physician advice to stay home during pandemic (H1N1) 2009: Results from the 2009 Queensland Social Survey BACKGROUND: One strategy available to public health officials during a pandemic is physician recommendations for isolation of infected individuals. This study was undertaken during the height of the Australian pandemic (H1N1) 2009 outbreak to measure self-reported willingness to comply with physician recommendations to stay home for seven days, and to compare responses for the current strain of pandemic influenza, avian influenza, seasonal influenza, and the common cold. METHODS: Data were collected as part of the Queensland Social Survey (QSS) 2009, which consisted of a standardized introduction, 37 demographic questions, and research questions incorporated through a cost-sharing arrangement. Four questions related to respondents' anticipated compliance with a physician's advice to stay home if they had a common cold, seasonal influenza, pandemic (H1N1) 2009 influenza or avian influenza were incorporated into QSS 2009, with responses recorded using a balanced Likert scale ranging from "very unlikely" to "very likely." Discordance between responses for different diseases was analysed using McNemar's test. Associations between demographic variables and anticipated compliance were analysed using Pearson's chi-square or chi-square for linear-by-linear association, and confirmed using multivariate logistic regression; p < 0.05 was used to establish statistical significance. RESULTS: Self-reported anticipated compliance increased from 59.9% for the common cold to 71.3% for seasonal influenza (p < .001), and to 95.0% for pandemic (H1N1) 2009 influenza and 94.7% for avian influenza (p < 0.001 for both versus seasonal influenza). Anticipated compliance did not differ for pandemic (H1N1) 2009 and avian influenza (p = 0.815). Age and sex were both associated with anticipated compliance in the setting of seasonal influenza and the common cold. Notably, 27.1% of health and community service workers would not comply with physician advice to stay home for seasonal influenza. CONCLUSIONS: Ninety-five percent of people report they would comply with a physicians' advice to stay home for seven days if they are diagnosed with pandemic (H1N1) 2009 or avian influenza, but only 71% can be expected to comply in the setting of seasonal influenza and fewer still can be expected to comply if they are diagnosed with a common cold. Sub-populations that might be worthwhile targets for public health messages aimed at increasing the rate of self-imposed isolation for seasonal influenza include males, younger people, and healthcare workers.

negative: The Impact of Social Distancing on the Transmission of Influenza Virus, South Korea, 2020

negative: Three Misunderstandings for Design of Negative Pressure Ward With the severe situation for the appearance of SARS and the fear for the resultant consequence, at the early stage of the outbreak event wards were reconstructed with a simple way. Newly constructed isolation wards were designed according to related literatures issued by CDC in 1994, and the corresponding requirements were elevated blindly. In literatures, the technical measures related to negative pressure isolation ward was inclined to adopt high negative pressure, air-tight door and all fresh air, where it was considered safe only to increase the negative pressure as high as possible, to install air-tight door without infiltration air and to provide all fresh air.

negative: Respiratory Viruses and Torque Teno Virus in Adults with Acute Respiratory Infections OBJECTIVE: To define the molecular epidemiology of respiratory viral infections in adult patients. METHODS: Nasal and throat swabs were collected from all adult patients with influenza-like illness (ILI), acute respiratory infection (ARI), or severe ARI (SARI) admitted to a tertiary hospital in Surakarta, Indonesia, between March 2010 and April 2011 and analyzed for 19 respiratory viruses and for torque teno virus (TTV) and human gyrovirus (HGyV). RESULTS: Respiratory viruses were detected in 61.3% of the subjects, most of whom had ARI (90.8%, OR = 11.39), were hospitalized (96.9%, OR = 22.31), had asthma exacerbation (90.9%, OR = 8.67), and/or had pneumonia (80%, OR = 4.0). Human rhinovirus (HRV) A43 predominated. Influenza A H3N2, human metapneumovirus (HMPV) subtypes A1 and A2, the influenza B virus, human adenovirus B, and human coronavirus OC43 were also detected. All respiratory viruses were detected in the transition month between the rainy and dry seasons. No mixed respiratory virus infection was found. Coinfections of the influenza A H3N2 virus with TTV, HMPV with TTV, HRV with TTV, and human parainfluenza virus-3 with TTV were found in 4.7, 2.8, 19.8, and 0.9% of the samples, respectively. CONCLUSIONS: This study highlights the need to perform routine detection of respiratory viruses in adults hospitalized with ARI, asthma exacerbation, and/or pneumonia.

negative: Clinical Characteristics of Critically Ill Patients Co-infected with SARS-CoV-2 and the Influenza Virus in Wuhan, China OBJECTIVE: To delineate the clinical characteristics of critically ill COVID-19 patients co-infected with influenza. METHODS: In this study, we included adult patients with laboratory-confirmed COVID-19 form Tongji Hospital (Wuhan, China), with or without influenza, and compared their clinical characteristics. RESULTS: Among 93 patients, 44 died and 49 were discharged. Forty-four (47.3%) were infected with influenza virus A and 2 (2.2%) with influenza virus B. Twenty-two (50.0%) of the non-survivors and 24 (49.0%) of the survivors were infected with the influenza virus. Critically ill COVID-19 patients with influenza were more prone to cardiac injury than those without influenza. For the laboratory indicators at admission, white blood cell counts, neutrophil counts, levels of tumor necrosis factor-α, D-dimer value, and proportion of elevated creatinine were higher in non-survivors with influenza than in those without influenza. CONCLUSION: The results showed a high proportion of COVID-19 patients were co-infected with influenza in Tongji Hospital, with no significant difference in the proportion of co-infection between survivors and non-survivors. The critically ill COVID-19 patients with influenza exhibited more severe inflammation and organ injury, indicating that co-infection with the influenza virus may induce an earlier and more frequently occurring cytokine storm.

negative: Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status Abstract Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and more severe diseases to include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A novel coronavirus was identified in December 2019 in Wuhan city, Hubei province, China. This virus represents a new strain that has not been previously identified in humans. The virus is now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease is called coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared the novel coronavirus outbreak a global pandemic in March 2020. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with more than 1,948,617 laboratory-confirmed cases and over 121,846 deaths worldwide. Currently, no specific medication is recommended to treat COVID-19 patients. However, governments and pharmaceutical companies are struggling to quickly find an effective drug to defeat the coronavirus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options. Favilavir is an antiviral drug that is approved in Japan for common influenza treatment and is now approved to treat symptoms of COVID-19 in China. Moreover, Chloroquine and hydroxychloroquine, drugs used to treat malaria and arthritis, respectively, were recommended by the National Health Commission of the People's Republic of China for treatment of COVID-19. Presently, chloroquine and hydroxychloroquine are under investigation by the US Food and Drug Administration (FDA) as a treatment for COVID-19. The first COVID-19 vaccine is not expected to be ready for clinical trials before the end of the year.

negative: Viral etiology and seasonality of influenza-like illness in Gabon, March 2010 to June 2011 BACKGROUND: Surveillance of influenza-like illness (ILI) in Central Africa began only recently, and few data are therefore available on the circulation of influenza virus and other respiratory viruses. In Gabon, a Central African country, we established a surveillance network in four major towns in order to analyze cases of ILI among patients who visited health centers between March 2010 and June 2011, and to determine the viral etiology. METHODS: Nasal swabs were sent for analysis to the Centre International de Recherches Médicales de Franceville, where they were screened for 17 respiratory viruses in a multiplex real-time reverse transcription polymerase chain reaction for all pathogens according the following pairs: adenovirus/parainfluenza virus 4, respiratory syncytial virus/human metapneumovirus, parainfluenza virus 1/parainfluenza virus 2, pandemic influenza virus A/seasonal influenza virus A (H1N1, H3N2)/seasonal influenza virus B, human coronaviruses 229E/OC43, human coronaviruses NL63/HKU1, rhinovirus/human parechovirus, and enterovirus/parainfluenza virus 3. RESULTS: We analyzed a total of 1041 specimens, of which 639 (61%) were positive for at least one virus. Three-quarters of the patients were children under five years old. We therefore focused on this age group, in which 68.1% of patients were positive for at least one virus. The most common viruses were adenoviruses (17.5%), followed by parainfluenza viruses (PIVs) 1–4 (16.8%), enteroviruses (EV) (14.7%), respiratory syncytial virus (RSV) (13.5%), and influenza virus (11.9%). The prevalence of some viruses was subject to geographic and seasonal variations. One-third of positive samples contained more than one virus. CONCLUSIONS: Like most studies in the world, the virus PIVs, EV, RSV, Influenza virus, HRV were predominant among children under five years old in Gabon. An exception is made for adenoviruses which have a high prevalence in our study. However adenoviruses can be detected in asymptomatic persons. These finding gave a better knowledge of the circulation and the seasonality of the viruses involved in ILI in Gabon.

negative: The most eagerly awaited summer of the Anthropocene: A perspective of SARS-CoV-2 decay and seasonal change Abstract To date, the world perhaps has never waited for the summer so impatiently in the entire Anthropocene, owing to the debate whether increasing temperature and humidity will decrease the environmental endurance of SARS-CoV-2. We present the perspective on the seasonal change on SARS-CoV-2 decay and COVID-19 spread. Our arguments are based on: i) structural similarity of coronavirus with several enteric viruses, and its vulnerability; ii) reports related to decay of those similar transmissible gastroenteritis viruses (TGEV) like norovirus and iii) improvement in the human immunity during summer with respect to winter. We present reasons why we can be optimistic about the slowdown of corona in the upcoming summer.

negative: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009–2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.

negative: Burden of influenza, healthcare seeking behaviour and hygiene measures during the A(H1N1)2009 pandemic in France: a population based study BACKGROUND: Influenza surveillance systems do not allow the identification of the true burden of illness caused by influenza in the community because they are restricted to consulting cases. A study was conducted to estimate the incidence and the burden of self-defined influenza, and to describe healthcare seeking behavior for self-defined influenza during the A(H1N1)2009 pandemic in the French population. METHODS: We conducted a random-based retrospective cross-sectional telephone survey between May 2009 and April 2010 among a random sample of the French population. RESULTS: For the 10 076 people included, 107 episodes of self-defined influenza were reported. The annual incidence of self-defined influenza was estimated at 13 942 cases per 100 000 inhabitants (CI95% 10 947 – 16 961), 62.1% (CI95% 50.5 – 72.5) of cases consulted a physician and 11.3% (CI95% 5.5 - 21.7) used a face mask. Following recommendations, 37.5% (CI95% 35.5 – 39.5) of people in the survey reported washing their hands more often during the pandemic season, and there was a positive association with being vaccinated against A(H1N1)2009 influenza, being a women, being a child (< 15 years) or living in a big city (≥ 100 000 inhabitants). CONCLUSIONS: Self-defined influenza causes a significant burden of illness in the French population and is a frequent cause for consultation. These results allow a more accurate interpretation of influenza surveillance data and an opportunity to adapt future health education messages.

negative: The site of origin of the 1918 influenza pandemic and its public health implications

negative: Animals and coronavirus, help for African labs and a short flu season

negative: Areas of academic research with the impact of COVID-19 Coronavirus (COVID-19) endemic is growing exponentially in the whole world. Researchers, technologists, doctors and other healthcare workers are working day and night on the development of vaccine and medicinesto control and treat this virus. SARS-CoV-2 is the name of the virus responsible for causing COVID-19 disease, which is highly infectious and lethal.With exponentially increasing infections, proportionate fatalities are being reported both from developed and under developed countries. As of today, more than one million people across the world have been reported infected with this virus, and more than 65,000 people have died of this disease. Hence, there is an urgent requirement for conducting academic research on several aspects of this highly contagious disease, to find effective means of containment and treatment of the disease, for now, and in future. We have identified some opportunities for academic research related to COVID-19 and have also provided suggestions to contain, prevent and treat this viral infection.

negative: After 2015: infectious diseases in a new era of health and development Running over timescales that span decades or centuries, the epidemiological transition provides the central narrative of global health. In this transition, a reduction in mortality is followed by a reduction in fertility, creating larger, older populations in which the main causes of illness and death are no longer acute infections of children but chronic diseases of adults. Since the year 2000, the Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment to low-income countries. Despite the successes of the MDGs era, the inhabitants of low-income countries still suffer an enormous burden of disease owing to diarrhoea, pneumonia, HIV/AIDS, tuberculosis, malaria and other pathogens. Adding to the predictable burden of endemic disease, the threat of pandemics is ever-present and global. With a view to the future, this review spotlights five aspects of the fight against infection beyond 2015, when the MDGs will be replaced by a new set of goals for poverty reduction and sustainable development. These aspects are: exploiting the biological links between infectious and non-infectious diseases; controlling infections among the new urban majority; enhancing the response to international health threats; expanding childhood immunization programmes to prevent acute and chronic diseases in adults; and working towards universal health coverage. By scanning the wider horizon now, infectious disease specialists have the chance to shape the post-2015 era of health and development.

negative: Upper respiratory infection during pregnancy and neurodevelopmental outcomes among offspring Abstract Objective Maternal infection during pregnancy is associated with psychiatric disorders among offspring. The aim of this study was to investigate associations between upper respiratory infection (URI) in pregnancy and measures of cognitive and behavioral outcomes in child offspring. Materials and methods A longitudinal study of 534 mother-child pairs with information regarding prenatal exposures collected through an interview conducted on average one year after delivery and subsequent participation in a childhood cognitive and psychosocial assessment between the ages 5–12years. Childhood cognition was measured using the Peabody Picture Vocabulary Test (PPVT-III) and the Beery-Buktenica Test of Visual Motor Integration-Fifth Edition (VMI-5) and behavioral function measured using the Child Behavior Checklist (CBCL) and teacher-report using the Teacher Report Form (TRF). Adjusted mean differences (adjMD) in outcome measures were calculated between mothers reporting the presence or absence of a URI during pregnancy. Results URI during pregnancy was not associated with the two measures of cognition given to offspring, but was associated with modest increases in total behavioral problems reported by mothers (adjMD: 3.72; CI: 1.91–5.54) and teachers (adjMD: 2.74; CI: 0.97–4.50). We observed differences in CBCL and TRF scores based on timing of URI: infections in mid-pregnancy (lunar months 4–5) were associated with poorer scores than were infections in early pregnancy (lunar months 2–3). Conclusions In general, URI in pregnancy was not associated with decrements in childhood cognition, but may be associated with behavior problems.

negative: Coronavirus (COVID-19) Classification using CT Images by Machine Learning Methods This study presents early phase detection of Coronavirus (COVID-19), which is named by World Health Organization (WHO), by machine learning methods. The detection process was implemented on abdominal Computed Tomography (CT) images. The expert radiologists detected from CT images that COVID-19 shows different behaviours from other viral pneumonia. Therefore, the clinical experts specify that COV\.ID-19 virus needs to be diagnosed in early phase. For detection of the COVID-19, four different datasets were formed by taking patches sized as 16x16, 32x32, 48x48, 64x64 from 150 CT images. The feature extraction process was applied to patches to increase the classification performance. Grey Level Co-occurrence Matrix (GLCM), Local Directional Pattern (LDP), Grey Level Run Length Matrix (GLRLM), Grey-Level Size Zone Matrix (GLSZM), and Discrete Wavelet Transform (DWT) algorithms were used as feature extraction methods. Support Vector Machines (SVM) classified the extracted features. 2-fold, 5-fold and 10-fold cross-validations were implemented during the classification process. Sensitivity, specificity, accuracy, precision, and F-score metrics were used to evaluate the classification performance. The best classification accuracy was obtained as 99.68% with 10-fold cross-validation and GLSZM feature extraction method.

negative: Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia BACKGROUND: A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients. METHODS: We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested. RESULTS: Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10(−4)-2000 TCID(50)/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. CONCLUSIONS: The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.

negative: Middle East respiratory syndrome coronavirus: transmission and phylogenetic evolution The Middle East respiratory syndrome coronavirus (MERS-CoV) was first described in 2012 and, subsequently, many cases were reported with a lower case fatality rate than initial cases. Humans can become infected within their communities and transmission can then be amplified in the healthcare setting. Contact investigation among cases shows a variable amount of spread among family members and healthcare workers. So far, circulating virus strains remain similar under continuous monitoring, with no genetic changes. Here, we discuss the transmission pattern, phylogenetic evolution, and pathogenesis of MERS-CoV infection.

negative: Type I and III interferons disrupt lung epithelial repair during recovery from viral infection Excessive cytokine signaling frequently exacerbates lung tissue damage during respiratory viral infection. Type I (IFN-α/β) and III (IFN-λ) interferons are host-produced antiviral cytokines. Prolonged IFN-α/β responses can lead to harmful proinflammatory effects, whereas IFN-λ mainly signals in epithelia, inducing localized antiviral immunity. Here we show that IFN signaling interferes with lung repair during influenza recovery, with IFN-λ driving these effects most potently. IFN-induced p53 directly reduces epithelial proliferation and differentiation, increasing disease severity, and susceptibility to bacterial superinfections. Thus, excessive or prolonged IFN-production aggravates viral infection by impairing lung epithelial regeneration. Therefore, timing and duration are critical parameters of endogenous IFN action and should be considered carefully for IFN therapeutic strategies against viral infections like influenza and coronavirus disease 2019 (COVID-19).

negative: MMDB: annotating protein sequences with Entrez's 3D-structure database Three-dimensional (3D) structure is now known for a large fraction of all protein families. Thus, it has become rather likely that one will find a homolog with known 3D structure when searching a sequence database with an arbitrary query sequence. Depending on the extent of similarity, such neighbor relationships may allow one to infer biological function and to identify functional sites such as binding motifs or catalytic centers. Entrez's 3D-structure database, the Molecular Modeling Database (MMDB), provides easy access to the richness of 3D structure data and its large potential for functional annotation. Entrez's search engine offers several tools to assist biologist users: (i) links between databases, such as between protein sequences and structures, (ii) pre-computed sequence and structure neighbors, (iii) visualization of structure and sequence/structure alignment. Here, we describe an annotation service that combines some of these tools automatically, Entrez's ‘Related Structure’ links. For all proteins in Entrez, similar sequences with known 3D structure are detected by BLAST and alignments are recorded. The ‘Related Structure’ service summarizes this information and presents 3D views mapping sequence residues onto all 3D structures available in MMDB ().

negative: COVID 19 and Spanish flu pandemics: All it changes, nothing changes The Corona Virus 19 (COVID 19) epidemic is an infectious disease which was declared as a pandemic and hit all the Countries, all over the world, from the beginning of the year 2020. There are many similarities between the COVID 19 epidemic and the Spanish flu epidemic. We considered some preventive measures which do not change in the two epidemics.

negative: HopPER: an adaptive model for probability estimation of influenza reassortment through host prediction BACKGROUND: Influenza reassortment, a mechanism where influenza viruses exchange their RNA segments by co-infecting a single cell, has been implicated in several major pandemics since 19th century. Owing to the significant impact on public health and social stability, great attention has been received on the identification of influenza reassortment. METHODS: We proposed a novel computational method named HopPER (Host-prediction-based Probability Estimation of Reassortment), that sturdily estimates reassortment probabilities through host tropism prediction using 147 new features generated from seven physicochemical properties of amino acids. We conducted the experiments on a range of real and synthetic datasets and compared HopPER with several state-of-the-art methods. RESULTS: It is shown that 280 out of 318 candidate reassortants have been successfully identified. Additionally, not only can HopPER be applied to complete genomes but its effectiveness on incomplete genomes is also demonstrated. The analysis of evolutionary success of avian, human and swine viruses generated through reassortment across different years using HopPER further revealed the reassortment history of the influenza viruses. CONCLUSIONS: Our study presents a novel method for the prediction of influenza reassortment. We hope this method could facilitate rapid reassortment detection and provide novel insights into the evolutionary patterns of influenza viruses.

negative: Mild COVID-19 infection despite chronic B cell depletion in a patient with aquaporin-4-positive neuromyelitis optica spectrum disorder Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2, which affects the lung and other organs. After an incubation period of 3-14 days, the infection presents with symptoms of variable severity, from mild flu-like disease to severe pneumonia and cytokine storm with increased mortality. Immunosuppressed patients may have higher risk of adverse outcomes; hence, there is an urgent need to evaluate the immune response and clinical outcomes of SARS-CoV-2 infection in these patients. Here, we report a 59-year-old woman with aquaporin-4-positive (AQPR4+) neuromyelitis Optica treated with rituximab who developed mild respiratory symptoms with COVID-19, despite B cell depletion at the time of infection.

negative: Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.

negative: Risk Overgeneralization in Times of a Contagious Disease Threat People’s assessment of risks is swayed by their current feelings. COVID-19 invokes powerful feelings because it is (i) a salient, enormous threat, (ii) unfamiliar, and (iii) intertwined with xenophobia. These three factors are known to exert predictable influence on people’s risk overgeneralization, policy preference, and sociopolitical attitudes. We provide a succinct, illustrative review of empirical work on these dynamics in times of a disease outbreak (e.g., the 2009 H1N1 swine flu, the 2014 Ebola). Theoretical and applied implications for the present COVID-19 pandemic include the value of salience in motivating public opinion change, the importance of reducing unfamiliarity for curbing risk-averse tendencies, and the need for policies that guard against xenophobia-driven racism in collaborative efforts.

negative: Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling SARS-COV-2 and all other coronaviruses express its 3 prime genes by forming sub-genomic RNA. As the genome of these virus exist in RNA form, only by profiling the relative abundance of these sgRNAs, can the viral transcriptome be revealed. Utilizing publically available meta-transcriptomic data generated from patient samples, we were able to infer the viral transcriptome in vivo, which is distinct from the in vitro one derived from cell culture. Inter-sample diversity was also observed and a sample specific transcript was identified. By doing the same analysis to MERS and SARS data, we were able to compare the three in terms of transcription. Among the differences, SARS-COV-2 has significantly elevated expression of the Spike gene, which may contribute to its high transmissibility. Highlights The in vivo transcriptome of SARS-CoV-2 revealed by sgRNA profiling, for 25 patient samples around the globe. The Spike protein expression is an order of magnitude higher in SARS-CoV-2 than MERS-CoV or SARS-CoV, possibly contributing to the virus’ elevated transmissibility. The in vivo SARS-CoV-2 transcriptomes, as inferred from human patient data was distinct from the in vitro one derived from cell line culture, all the accessory genes were up-regulated in vivo, suggesting intricate expression regulation mechanism for the small viral genome.

negative: Monitoring trends and differences in COVID-19 case fatality rates using decomposition methods: Contributions of age structure and age-specific fatality The population-level case fatality rate (CFR) associated with COVID-19 varies substantially, both across countries and within countries over time. We analyze the contribution of two key determinants of the variation in the observed CFR: the age-structure of diagnosed infection cases and age-specific case-fatality rates. We use data on diagnosed COVID-19 cases and death counts attributable to COVID-19 by age for China, France, Germany, Italy, South Korea, Spain, and the United States. We calculate the CFR for each country at the latest data point and for Italy also over time. We use demographic decomposition to break the difference between CFRs into unique contributions arising from the age-structure of confirmed cases and the age-specific case-fatality. CFRs vary from 0.7% in Germany and 1.6% in South Korea to 8.6% in Spain and 10.6% in Italy. The age-structure of detected cases can explain a substantial proportion of cross-country variation in the CFR. For example, 57% of Spain's difference with respect to South Korea is explained by the observed cases being older. In Italy, the CFR increased from 4.2% to 10.6% between March 9 and March 29, 2020, and more than 95% of the change was due to increasing age-specific case fatality rates. The importance of the age-structure of infected cases likely reflects several factors, including different testing regimes and differences in transmission trajectories; while increasing age-specific case fatality rates indicate the worsening health outcomes of those infected with COVID-19. Our findings lend support to recommendations for data to be disaggregated by age, and potentially other variables, to facilitate a better understanding of population-level differences in CFRs. They also show the need for well designed seroprevalence studies to ascertain the extent to which differences in testing regimes drive differences in the age-structure of detected cases.

negative: Cross-Country Age Disparities in COVID-19 Cases with Hospitalization, ICU Usage, and Morbidity In this paper, we examine cross-country differences, in terms of the age distribution of symptomatic cases, hospitalizations, intensive care unit (ICU) cases, and fatalities due to the novel COVID-19. By calculating conditional probabilities, we bridge country-level incidence data gathered from different countries and attribute the variability in data to country demographics. We then provide case, hospitalization, ICU, and fatality estimates for a comprehensive list of countries using the existing data from a variety of countries.

negative: Influenza Virus: A Brief Overview Influenza is a major public health concern, infecting 5–15% of the global population annually. Influenza virus belongs to family Orthomyxoviridae, and has three types A, B and C. Infection by influenza virus A is most common and severe, generally found in humans. It spreads rapidly and affects human population across large geographical region within short period of time with varying degree of pathology from mild to severe. Wild aquatic birds and other animal species like birds, pigs, ferret, horses, seals, whales, mink, giant anteaters, cats and dogs are the reservoir for the influenza A virus. Influenza B and C viruses have very limited host range and appear predominantly in humans. Influenza virus gains pandemic potential through genetic reassortment called “genetic shift” with complete renewal of surface antigen and a small but gradual genetic change by mutations which make it to adapt efficiently in human population called “genetic drift”. Although, the epidemiology related to influenza infection has been studied from several years but some facts associated to disease transmission has poorly understood. This article reviews the important aspects of virological, epidemiological and clinical features related to influenza virus for better understanding of disease transmission and its pathogenesis.

negative: Novel Coronavirus (COVID-19) Knowledge and Perceptions: A Survey of Healthcare Workers Background: During the first week of March, the surge of coronavirus disease 2019 (COVID-19) cases reached over 100 countries with more than 100,000 cases. Healthcare authorities have already initiated awareness and preparedness activities beyond borders. A poor understanding of the disease among healthcare workers (HCWs) may result in delayed treatment and the rapid spread of infection. This study aimed to investigate the knowledge and perceptions of HCWs about COVID-19. Methods: A cross-sectional, web-based study was conducted among HCWs about COVID-19 during the first week of March 2020. A 23-item survey instrument was developed and distributed randomly to HCWs using social media; it required 5 minutes to complete. A chi-square test was used to investigate the level of association among variables at the significance level of p<0.05. Results: Of 529 participants, a total of 453 HCWs completed the survey (response rate: 85.6%); 51.6% were males, 32.1% were aged 25-34 years, and most were doctors (30.2%) and medical students (29.6%). Regarding COVID-19, most of the participants used social media to obtain information (61%), and a significant proportion of HCWs had poor knowledge of its transmission (61%) and symptom onset (63.6%) and showed positive perceptions of COVID-19 prevention and control. Factors such as age and profession were associated with inadequate knowledge and poor perception of COVID-19. Conclusion: As the global threat of COVID-19 continues to emerge, it is critical to improve the knowledge and perceptions of HCWs. Educational interventions are urgently needed to reach HCWs beyond borders, and further studies are warranted.

negative: Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd Abstract In 2012 in Jordan, infection by a novel coronavirus (CoV) caused the first known cases of Middle East respiratory syndrome (MERS). MERS-CoV sequences have since been found in a bat and the virus appears to be enzootic among dromedary camels across the Arabian Peninsula and in parts of Africa. The majority of human cases have occurred in the Kingdom of Saudi Arabia (KSA). In humans, the etiologic agent, MERS-CoV, has been detected in severe, mild and influenza-like illness and in those without any obvious signs or symptoms of disease. MERS is often a lower respiratory tract disease associated with fever, cough, breathing difficulties, pneumonia that can progress to acute respiratory distress syndrome, multiorgan failure and death among more than a third of those infected. Severe disease is usually found in older males and comorbidities are frequently present in cases of MERS. Compared to SARS, MERS progresses more rapidly to respiratory failure and acute kidney injury, is more often observed as severe disease in patients with underlying illnesses and is more often fatal. MERS-CoV has a broader tropism than SARS-CoV, rapidly triggers cellular damage, employs a different receptor and induces a delayed proinflammatory response in cells. Most human cases have been linked to lapses in infection prevention and control in healthcare settings, with a fifth of virus detections reported among healthcare workers. This review sets out what is currently known about MERS and the MERS-CoV, summarises the new phenomenon of crowd-sourced epidemiology and lists some of the many questions that remain unanswered, nearly three years after the first reported case.

negative: SARS-CoV-2 epidemiology and control, different scenarios for Turkey BACKGROUND/AIM: Coronavirus Infectious Disease 2019 (COVID-19) is now a pandemic spreading in most countries including Turkey. MATERIALS AND METHODS: The current knowledge of COVID-19 and the virus causing it, SARS-CoV-2, was reviewed. The epidemiology and control in different countries was compared and the differences discussed. RESULTS: The population attack rates and case fatality rates vary from country to country with Lombardy in northern Italy reporting an attack rate in the general population of 0.37% compared to 0.004% in Hong Kong. The differences are caused by different testing strategies and reporting systems. CONCLUSION: Turkey is early in the outbreak. Different control strategies are available with South Korea, Hong Kong and Singapore being models to follow.

negative: Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19) To understand the severity of infection for a given disease, it is common epidemiological practice to estimate the case fatality risk, defined as the risk of death among cases. However, there are three technical obstacles that should be addressed to appropriately measure this risk. First, division of the cumulative number of deaths by that of cases tends to underestimate the actual risk because deaths that will occur have not yet observed, and so the delay in time from illness onset to death must be addressed. Second, the observed dataset of reported cases represents only a proportion of all infected individuals and there can be a substantial number of asymptomatic and mildly infected individuals who are never diagnosed. Third, ascertainment bias and risk of death among all those infected would be smaller when estimated using shorter virus detection windows and less sensitive diagnostic laboratory tests. In the ongoing COVID-19 epidemic, health authorities must cope with the uncertainty in the risk of death from COVID-19, and high-risk individuals should be identified using approaches that can address the abovementioned three problems. Although COVID-19 involves mostly mild infections among the majority of the general population, the risk of death among young adults is higher than that of seasonal influenza, and elderly with underlying comorbidities require additional care.

negative: Reproduction of East-African bats may guide risk mitigation for coronavirus spillover BACKGROUND: Bats provide important ecosystem services; however, current evidence supports that they host several zoonotic viruses, including species of the Coronaviridae family. If bats in close interaction with humans host and shed coronaviruses with zoonotic potential, such as the Severe Acute Respiratory Syndrome virus, spillover may occur. Therefore, strategies aiming to mitigate potential spillover and disease emergence, while supporting the conservation of bats and their important ecological roles are needed. Past research suggests that coronavirus shedding in bats varies seasonally following their reproductive cycle; however, shedding dynamics have been assessed in only a few species, which does not allow for generalization of findings across bat taxa and geographic regions. METHODS: To assess the generalizability of coronavirus shedding seasonality, we sampled hundreds of bats belonging to several species with different life history traits across East Africa at different times of the year. We assessed, via Bayesian modeling, the hypothesis that chiropterans, across species and spatial domains, experience seasonal trends in coronavirus shedding as a function of the reproductive cycle. RESULTS: We found that, beyond spatial, taxonomic, and life history differences, coronavirus shedding is more expected when pups are becoming independent from the dam and that juvenile bats are prone to shed these viruses. CONCLUSIONS: These findings could guide policy aimed at the prevention of spillover in limited-resource settings, where longitudinal surveillance is not feasible, by identifying high-risk periods for coronavirus shedding. In these periods, contact with bats should be avoided (for example, by impeding or forbidding people access to caves). Our proposed strategy provides an alternative to culling – an ethically questionable practice that may result in higher pathogen levels – and supports the conservation of bats and the delivery of their key ecosystem services.

negative: Vitamin D: A simpler alternative to tocilizumab for trial in COVID-19? There is anecdotal evidence that tocilizumab, an immunosuppressant drug, may be a potential therapeutic option for patients with severe manifestations of coronavirus disease 2019 (COVID-19). Like tocilizumab, Vitamin D appears to modulate the activity of an interleukin (IL-6), which may explain the seasonal variation in prevalence of influenza. While most cases of COVID-19 have, thus far, occurred in the Northern Hemisphere winter, limiting the ability to assess seasonal variation, there remains substantial variation in the severity of this condition that has yet to be explained. A retrospective comparison of Vitamin D levels in previously obtained blood samples between survivors and confirmed fatalities could establish a rationale for implementation of widespread Vitamin D supplementation. This would be far cheaper and simpler than tocilizumab as a therapeutic option to trial.

negative: Epidemic Influenza Seasons from 2008 to 2018 in Poland: A Focused Review of Virological Characteristics The objective of this review was to elaborate on changes in the virological characteristics of influenza seasons in Poland in the past decade. The elaboration was based on the international influenza surveillance system consisting of Sentinel and non-Sentinel programs, recently adopted by Poland, in which professionals engaged in health care had reported tens of thousands of cases of acute upper airway infections. The reporting was followed by the provision of biological specimens collected from patients with suspected influenza and influenza-like infection, in which the causative contagion was then verified with molecular methods. The peak incidence of influenza infections has regularly been in January–March each epidemic season. The number of tested specimens ranged from 2066 to 8367 per season from 2008/2009 to 2017/2018. Type A virus predominated in nine out of the ten seasons and type B virus of the Yamagata lineage in the 2017/2018 season. Concerning the influenza-like infection, respiratory syncytial virus predominated in all the seasons. There was a sharp increase in the proportion of laboratory confirmations of influenza infection from season to season in relation to the number of specimens examined, from 3.2% to 42.4% over the decade. The number of confirmations, enabling a prompt commencement of antiviral treatment, related to the number of specimens collected from patients and on the virological situation in a given season. Yet influenza remains a health scourge, with a dismally low yearly vaccination rate, which recently reaches just about 3.5% of the general population in Poland.

negative: Examining the knowledge, attitudes and practices of domestic and international university students towards seasonal and pandemic influenza BACKGROUND: Prior to the availability of the specific pandemic vaccine, strategies to mitigate the impact of the disease typically involved antiviral treatment and “non-pharmaceutical” community interventions. However, compliance with these strategies is linked to risk perceptions, perceived severity and perceived effectiveness of the strategies. In 2010, we undertook a study to examine the knowledge, attitudes, risk perceptions, practices and barriers towards influenza and infection control strategies amongst domestic and international university students. METHODS: A study using qualitative methods that incorporated 20 semi-structured interviews was undertaken with domestic and international undergraduate and postgraduate university students based at one university in Sydney, Australia. Participants were invited to discuss their perceptions of influenza (seasonal vs. pandemic) in terms of perceived severity and impact, and attitudes towards infection control measures including hand-washing and the use of social distancing, isolation or cough etiquette. RESULTS: While participants were generally knowledgeable about influenza transmission, they were unable to accurately define what ‘pandemic influenza’ meant. While avian flu or SARS were mistaken as examples of past pandemics, almost all participants were able to associate the recent “swine flu” situation as an example of a pandemic event. Not surprisingly, it was uncommon for participants to identify university students as being at risk of catching pandemic influenza. Amongst those interviewed, it was felt that ‘students’ were capable of fighting off any illness. The participant’s nominated hand washing as the most feasible and acceptable compared with social distancing and mask use. CONCLUSIONS: Given the high levels of interaction that occurs in a university setting, it is really important that students are informed about disease transmission and about risk of infection. It may be necessary to emphasize that pandemic influenza could pose a real threat to them, that it is important to protect oneself from infection and that infection control measures can be effective.

negative: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.

negative: Characterization of Influenza Virus Pseudotyped with Ebolavirus Glycoprotein We have produced a new Ebola virus pseudotype, E-S-FLU, that can be handled in biosafety level 1/2 containment for laboratory analysis. The E-S-FLU virus is a single-cycle influenza virus coated with Ebolavirus glycoprotein, and it encodes enhanced green fluorescence protein as a reporter that replaces the influenza virus hemagglutinin. MDCK-SIAT1 cells were transduced to express Ebolavirus glycoprotein as a stable transmembrane protein for E-S-FLU virus production. Infection of cells with the E-S-FLU virus was dependent on the Niemann-Pick C1 protein, which is the well-characterized receptor for Ebola virus entry at the late endosome/lysosome membrane. The E-S-FLU virus was neutralized specifically by an anti-Ebolavirus glycoprotein antibody and a variety of small drug molecules that are known to inhibit the entry of wild-type Ebola virus. To demonstrate the application of this new Ebola virus pseudotype, we show that a single laboratory batch was sufficient to screen a library (LOPAC(1280); Sigma) of 1,280 pharmacologically active compounds for inhibition of virus entry. A total of 215 compounds inhibited E-S-FLU virus infection, while only 22 inhibited the control H5-S-FLU virus coated in H5 hemagglutinin. These inhibitory compounds have very dispersed targets and mechanisms of action, e.g., calcium channel blockers, estrogen receptor antagonists, antihistamines, serotonin uptake inhibitors, etc., and this correlates with inhibitor screening results obtained with other pseudotypes or wild-type Ebola virus in the literature. The E-S-FLU virus is a new tool for Ebola virus cell entry studies and is easily applied to high-throughput screening assays for small-molecule inhibitors or antibodies. IMPORTANCE Ebola virus is in the Filoviridae family and is a biosafety level 4 pathogen. There are no FDA-approved therapeutics for Ebola virus. These characteristics warrant the development of surrogates for Ebola virus that can be handled in more convenient laboratory containment to study the biology of the virus and screen for inhibitors. Here we characterized a new surrogate, named E-S-FLU virus, that is based on a disabled influenza virus core coated with the Ebola virus surface protein but does not contain any genetic information from the Ebola virus itself. We show that E-S-FLU virus uses the same cell entry pathway as wild-type Ebola virus. As an example of the ease of use of E-S-FLU virus in biosafety level 1/2 containment, we showed that a single production batch could provide enough surrogate virus to screen a standard small-molecule library of 1,280 candidates for inhibitors of viral entry.

negative: The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly Public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. A negative binomial model was developed to estimate Taiwan's monthly influenza-associated mortality among the elderly. We calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (P&I), respiratory and circulatory, and all-cause] from the 1999–2000 through the 2006–2007 influenza seasons. Obtaining influenza virus sequences from the months/years in which death from P&I was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin 1 (HA1) of the circulating and vaccine strains. We found that the higher the isolation rate of A (H3N2) and vaccine-mismatched influenza viruses, the greater the monthly P&I mortality. However, this significant positive association became negative for higher matching of A (H3N2) and public health efforts with post-SARS effect. Mean excess P&I mortality for winters was significantly higher before 2003 than after that year [mean ± S.D.: 1.44±1.35 vs. 0.35±1.13, p = 0.04]. Further analysis revealed that vaccine-matched circulating influenza A viruses were significantly associated with lower excess P&I mortality during post-SARS winters (i.e., 2005–2007) than during pre-SARS winters [0.03±0.06 vs. 1.57±1.27, p = 0.01]. Stratification of these vaccine-matching and post-SARS effect showed substantial trends toward lower elderly excess P&I mortalities in winters with either mismatching vaccines during the post-SARS period or matching vaccines during the pre-SARS period. Importantly, all three excess mortalities were at their highest in May, 2003, when inter-hospital nosocomial infections were peaking. Furthermore, vaccine-mismatched H3N2 viruses circulating in the years with high excess P&I mortality exhibited both a lower amino acid identity percentage of HA1 between vaccine and circulating strains and a higher numbers of variations at epitope B. Our model can help future decision makers to estimate excess P&I mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness.

negative: Ecosystem approaches to the risk for schizophrenia

negative: Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak Abstract Background In response to the novel influenza A H1N1 outbreak in the NY City area, 6090 patient samples were submitted over a 5-week period for a total of 14,114 viral diagnostic tests, including rapid antigen, direct immunofluorescence (DFA), viral culture and PCR. Little was known about the performance of the assays for the detection of novel H1N1 in the background of seasonal H1N1, H3N2 and other circulating respiratory viruses. In addition, subtyping influenza A became critical for the identification of high risk and/or hospitalized patients with novel H1N1 infection and for monitoring the spread of the outbreak. Study design This study analyzed the performances of the BinaxNOW Influenza A&B test (BinaxNOW), the 3M Rapid Detection Flu A+B test (3MA+B), direct immunofluorescence, R-Mix culture and the Luminex xTAG Respiratory Virus Panel (RVP) for the detection of seasonal influenza, novel H1N1 and other respiratory viruses. RVP was also evaluated for its ability to differentiate seasonal H1N1, H3N2 and novel H1N1. Results The sensitivities, specificities, PPVs and NPVs for the detection of novel H1N1, determined by comparing all four-test methods, were: rapid antigen: 17.8%, 93.6%, 77.4%, 47.9%; DFA: 46.7%, 94.5%, 91.3%, 58.9%; R-Mix culture: 88.9%, 100%, 100%, 87.9%; RVP: 97.8%, 100%, 100%, 97.3%. The individual sensitivities of BinaxNOW and 3MA+B as compared to R-Mix culture for the detection of novel H1N1 were 9.6% and 40%, respectively. All unsubtypeable influenza A specimens identified by RVP and tested with the CDC novel H1N1 specific RT-PCR assay were confirmed to be novel H1N1. Conclusions Rapid antigen tests, DFA, R-Mix culture and the xTAG RVP test all detected the novel H1N1 strain, but with highly varied sensitivity. The RVP test provided the best diagnostic option as RVP demonstrated superior sensitivity for the detection of all influenza strains, including the novel H1N1, provided accurate influenza A subtyping and identified a significant number of additional respiratory pathogens.

negative: Computational analysis of SARS-CoV-2/COVID-19 surveillance by wastewater-based epidemiology locally and globally: Feasibility, economy, opportunities and challenges Abstract With the economic and practical limits of medical screening for SARS-CoV-2/COVID-19 coming sharply into focus worldwide, scientists are turning now to wastewater-based epidemiology (WBE) as a potential tool for assessing and managing the pandemic. We employed computational analysis and modeling to examine the feasibility, economy, opportunities and challenges of enumerating active coronavirus infections locally and globally using WBE. Depending on local conditions, detection in community wastewater of one symptomatic/asymptomatic infected case per 100 to 2,000,000 non-infected people is theoretically feasible, with some practical successes now being reported from around the world. Computer simulations for past, present and emerging epidemic hotspots (e.g., Wuhan, Milan, Madrid, New York City, Teheran, Seattle, Detroit and New Orleans) identified temperature, average in-sewer travel time and per-capita water use as key variables. WBE surveillance of populations is shown to be orders of magnitude cheaper and faster than clinical screening, yet cannot fully replace it. Cost savings worldwide for one-time national surveillance campaigns are estimated to be in the million to billion US dollar range (US$), depending on a nation's population size and number of testing rounds conducted. For resource poor regions and nations, WBE may represent the only viable means of effective surveillance. Important limitations of WBE rest with its inability to identify individuals and to pinpoint their specific locations. Not compensating for temperature effects renders WBE data vulnerable to severe under-/over-estimation of infected cases. Effective surveillance may be envisioned as a two-step process in which WBE serves to identify and enumerate infected cases, where after clinical testing then serves to identify infected individuals in WBE-revealed hotspots. Data provided here demonstrate this approach to save money, be broadly applicable worldwide, and potentially aid in precision management of the pandemic, thereby helping to accelerate the global economic recovery that billions of people rely upon for their livelihoods.

negative: A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses Feline coronavirus (FCoV) is a complex viral agent that causes a variety of clinical manifestations in cats, commonly known as feline infectious peritonitis (FIP). It is recognized that FCoV can occur in two different serotypes. However, differences in the S protein are much more than serological or antigenic variants, resulting in the effective presence of two distinct viruses. Here, we review the distinct differences in the S proteins of these viruses, which are likely to translate into distinct biological outcomes. We introduce a new concept related to the non-taxonomical classification and differentiation among FCoVs by analyzing and comparing the genetic, structural, and functional characteristics of FCoV and the FCoV S protein among the two serotypes and FCoV biotypes. Based on our analysis, we suggest that our understanding of FIP needs to consider whether the presence of these two distinct viruses has implications in clinical settings.

negative: Influenza A(H1N1)pdm09 and flu response centres: Characteristics of flu response centre staff in the West Midlands Summary Objective To assess the operational experience and knowledge of staff who worked in the West Midlands Flu Response Centre (FRC) during the ‘containment’ phase of influenza A(H1N1)pdm09. Study design Evaluation study. Methods Cross-sectional survey of staff who worked in the West Midlands FRC between 18 May 2009 and 10 July 2009 using an online self-administered questionnaire. The questionnaire included sections related to the respondents' FRC experience, knowledge about influenza A(H1N1)pdm09 and the containment phase. Results This study had a 51% (89/176) response rate. Of the respondents, 59% were female, 64% were of White ethnicity, 55% were clinicians, 46% were aged 25–44 years, and 67% had no previous call centre experience. A significant proportion (P < 0.001) of respondents believed that the FRC had made a positive contribution to the public health management of the containment phase. Nearly all respondents indicated that they were familiar with the terms ‘pandemic flu’ or ‘influenza pandemic’ (99%), understood the aim of the containment phase (90%), and knew the severity of the illness caused by the virus (97%). However, specific knowledge was lacking regarding a number of public health interventions, and overall knowledge scores for clinicians and non-clinicians were similar. Conclusion This study is the first to report on the characteristics of FRC staff during the containment phase of influenza A(H1N1)pdm09 pandemic. Although overall, staff evaluation of the West Midlands FRC was very positive, a number of knowledge gaps were identified. This study provides valuable insights which can contribute to preparedness planning.

negative: Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002–2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.

negative: Communicating uncertainty - how Australian television reported H1N1 risk in 2009: a content analysis BACKGROUND: Health officials face particular challenges in communicating with the public about emerging infectious diseases of unknown severity such as the 2009 H1N1(swine 'flu) pandemic (pH1N1). Statements intended to create awareness and convey the seriousness of infectious disease threats can draw accusations of scare-mongering, while officials can be accused of complacency if such statements are not made. In these communication contexts, news journalists, often reliant on official sources to understand issues are pivotal in selecting and emphasising aspects of official discourse deemed sufficiently newsworthy to present to the public. This paper presents a case-study of news communication regarding the emergence of pH1N1. METHODS: We conducted a content analysis of all television news items about pH1N1. We examined news and current affairs items broadcast on 5 free-to-air Sydney television channels between April 25 2009 (the first report) and October 9 (prior to the vaccine release) for statements about [1] the seriousness of the disease [2] how the public could minimise contagion [3] government responses to emerging information. RESULTS: pH1N1 was the leading health story for eight of 24 weeks and was in the top 5 for 20 weeks. 353 news items were identified, yielding 3086 statements for analysis, with 63.4% related to the seriousness of the situation, 12.9% providing advice for viewers and 23.6% involving assurances from government. Coverage focused on infection/mortality rates, the spread of the virus, the need for public calm, the vulnerability of particular groups, direct and indirect advice for viewers, and government reassurances about effective management. CONCLUSIONS: Overall, the reporting of 2009 pH1N1 in Sydney, Australia was generally non-alarmist, while conveying that pH1N1 was potentially serious. Daily infection rate tallies and commentary on changes in the pandemic alert level were seldom contextualised to assist viewers in understanding personal relevance. Suggestions are made about how future reporting of emerging infectious diseases could be enhanced.

negative: A “One-Health” approach for diagnosis and molecular characterization of SARS-CoV-2 in Italy Abstract The current pandemic is caused by a novel coronavirus (CoV) called SARS-CoV-2 (species Severe acute respiratory syndrome-related coronavirus, subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae). In Italy, up to the 2nd of April 2020, overall 139,422 confirmed cases and 17,669 deaths have been notified, while 26,491 people have recovered. Besides the overloading of hospitals, another issue to face was the capacity to perform thousands of tests per day. In this perspective, to support the National Health Care System and to minimize the impact of this rapidly spreading virus, the Italian Ministry of Health involved the Istituti Zooprofilattici Sperimentali (IZSs), Veterinary Public Health Institutes, in the diagnosis of SARS-CoV-2 by testing human samples. IZSAM, is currently testing more than 600 samples per day and WGS from positive samples. Sequence analysis of these samples suggested that outbreaks in Abruzzo region may be related to outbreaks of northern Italy and northern Europe, these latter as for the presence of mutations in the N protein. CoVs, and related diseases, are well known to veterinarians since decades. The experience that veterinarians operating within the Public health system gained in the control and characterization of previous health issues of livestock and poultry including avian flu, bluetongue, foot and mouth disease, responsible for huge economic losses, is certainly of great help to minimize the impact of this global crisis.

negative: [Whether conjunctival congestion in patients infected with 2019 novel coronavirus is definitely related the novel coronavirus?] Currently, it is commonly reported that COVID-19 patients are associated with conjunctival congestion and other symptoms, and the transmission route or high-risk diseases of ophthalmology and high-risk working status are speculated. Are conjunctival congestion or conjunctival related symptoms in patients with 2019 novel coronavirus definitely related the novel coronavirus? Conjunctival congestion is one of the common clinical signs of various types of conjunctivitis. The symptoms and signs of conjunctivitis in COVID-19 patients may be related to a variety of factors. Therefore, conjunctival symptoms should not be associated with 2019 novel coronavirus without evidence. ( Chin J Ophthalmol, 2020, 56: ).

negative: Asymptomatic Shedding of Respiratory Virus among an Ambulatory Population across Seasons Most observation of human respiratory virus carriage is derived from medical surveillance; however, the infections documented by this surveillance represent only a symptomatic fraction of the total infected population. As the role of asymptomatic infection in respiratory virus transmission is still largely unknown and rates of asymptomatic shedding are not well constrained, it is important to obtain more-precise estimates through alternative sampling methods. We actively recruited participants from among visitors to a New York City tourist attraction. Nasopharyngeal swabs, demographics, and survey information on symptoms, medical history, and recent travel were obtained from 2,685 adults over two seasonal arms. We used multiplex PCR to test swab specimens for a selection of common respiratory viruses. A total of 6.2% of samples (168 individuals) tested positive for at least one virus, with 5.6% testing positive in the summer arm and 7.0% testing positive in the winter arm. Of these, 85 (50.6%) were positive for human rhinovirus (HRV), 65 (38.7%) for coronavirus (CoV), and 18 (10.2%) for other viruses (including adenovirus, human metapneumovirus, influenza virus, and parainfluenza virus). Depending on the definition of symptomatic infection, 65% to 97% of infections were classified as asymptomatic. The best-fit model for prediction of positivity across all viruses included a symptom severity score, Hispanic ethnicity data, and age category, though there were slight differences across the seasonal arms. Though having symptoms is predictive of virus positivity, there are high levels of asymptomatic respiratory virus shedding among the members of an ambulatory population in New York City. IMPORTANCE Respiratory viruses are common in human populations, causing significant levels of morbidity. Understanding the distribution of these viruses is critical for designing control methods. However, most data available are from medical records and thus predominantly represent symptomatic infections. Estimates for asymptomatic prevalence are sparse and span a broad range. In this study, we aimed to measure more precisely the proportion of infections that are asymptomatic in a general, ambulatory adult population. We recruited participants from a New York City tourist attraction and administered nasal swabs, testing them for adenovirus, coronavirus, human metapneumovirus, rhinovirus, influenza virus, respiratory syncytial virus, and parainfluenza virus. At recruitment, participants completed surveys on demographics and symptomology. Analysis of these data indicated that over 6% of participants tested positive for shedding of respiratory virus. While participants who tested positive were more likely to report symptoms than those who did not, over half of participants who tested positive were asymptomatic.

negative: Chapter 8 Virus Evolution and Genetics Abstract Viruses are very diverse and they infect organisms from all domains of life and across all ecosystems, but related viruses often infect very different types of organisms, pointing to their very ancient origins. Three commonly proposed mechanisms for the origins of viruses are: Viruses descended from primitive precellular life forms; viruses are escaped cellular genetic elements; viruses devolved from more complex intracellular parasites. None of these theories easily explains the origins of all viruses and it is widely accepted that all viruses did not share a single common ancestor. Instead, distinct lineages of viruses probably evolved by different mechanism. There is also good evidence that viruses have shaped the evolution of their hosts, for at least hundreds of millions of years. While some virologists consider the ancient origins of viruses, others examine the forces that drive virus evolution today. Examples of ongoing virus evolution include: Cross-species jumps; decreased or increased virulence; emergence of drug resistance; escape from immune responses at the level of individuals and populations. Virus evolution is the outcome of two independent events. The first is genome mutation and the second is selection. Viruses with RNA genomes tend to have high mutation rates, but some appear to be evolutionarily stable nonetheless. Viruses have distinct phenotypes. For examples, some influenza viruses are highly virulent but others are much less so; influenza viruses also differ tremendously in their ability to be transmitted. Modern studies of virus genetics seek to correlate diverse phenotypes with specific genes and sequences. The ability to do reverse genetics is key to understanding viral genes. Reverse genetics involves cloning viral genomes, designing specific mutation, and introducing the mutated genomes back into cells to produce infectious particles whose phenotypes can then be measured.

negative: Adenovirus-Based Vectors for the Development of Prophylactic and Therapeutic Vaccines Emerging and reemerging infectious diseases as well as cancer pose great global health impacts on the society. Vaccines have emerged as effective treatments to prevent or reduce the burdens of already developed diseases. This is achieved by means of activating various components of the immune system to generate systemic inflammatory reactions targeting infectious agents or diseased cells for control/elimination. DNA virus-based genetic vaccines gained significant attention in the past decades owing to the development of DNA manipulation technologies, which allowed engineering of recombinant viral vectors encoding sequences for foreign antigens or their immunogenic epitopes as well as various immunomodulatory molecules. Despite tremendous progress in the past 50 years, many hurdles still remain for achieving the full clinical potential of viral-vectored vaccines. This chapter will present the evolution of vaccines from “live” or “attenuated” first-generation agents to recombinant DNA and viral-vectored vaccines. Particular emphasis will be given to human adenovirus (Ad) for the development of prophylactic and therapeutic vaccines. Ad biological properties related to vaccine development will be highlighted along with their advantages and potential hurdles to be overcome. In particular, we will discuss (1) genetic modifications in the Ad capsid protein to reduce the intrinsic viral immunogenicity, (2) antigen capsid incorporation for effective presentation of foreign antigens to the immune system, (3) modification of the hexon and fiber capsid proteins for Ad liver de-targeting and selective retargeting to cancer cells, (4) Ad-based vaccines carrying “arming” transgenes with immunostimulatory functions as immune adjuvants, and (5) oncolytic Ad vectors as a new therapeutic approach against cancer. Finally, the combination of adenoviral vectors with other non-adenoviral vector systems, the prime/boost strategy of immunization, clinical trials involving Ad-based vaccines, and the perspectives for the field development will be discussed.

negative: Management of Respiratory Disorders and the Pharmacist's Role: Cough, Colds, and Sore Throats and Allergies (Including Eyes) Abstract Complaints pertaining to the upper respiratory tract, such as the common cold and allergies, are a common reason for presentation to community pharmacies. This chapter explores the common cold and influenza and associated symptoms, including cough, congestion, rhinorrhea, sore throat, diarrhea, pain, and fever. This chapter will aid pharmacists in identifying the characteristics and pharmacological and nonpharmacological management of these conditions. Allergies of the nose and eyes are another common ailment encountered in the community pharmacy, and this chapter assists pharmacists in reaching a differential diagnosis and strategies to manage these conditions.

negative: On Answering the Call to Action for COVID-19: Continuing a Bold Legacy of Health Advocacy The disproportionately high burden of death and disability observed for racial and ethnic minorities under the Coronavirus pandemic necessitates sustained advocacy by the medical and public health communities around critical determinants of population health. Prompting our advocacy should be the understanding that our collective ability to rebound from such crises may ultimately hinge on protecting and equipping our most vulnerable racial-ethnic minority groups and any susceptible individuals within those populations. If proven effective, recent historic firsts by the U.S. Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), the Office of Minority Health (OMH) and the Centers for Disease Control and Prevention (CDC) in response to COVID-19 should be championed for permanency within policy, practice and funding. In addition, given the complex history of Black Americans in this country and persistent and substantial Black-white disparities on health and economic measures across the board, some kind of reparations for this group may serve as a logical starting point for further advocacy. Nevertheless, we remain supportive allies of all organizations concerned with communities who suffer the weight of this pandemic and any future world health disasters. Let us as human clinicians and public health professionals capture this moment of challenge and engage in thoughtful unification of effort and commit to measurable progress for as long as the need exists and certainly for the foreseeable future.

negative: Medical Anthropology Medical anthropology is an interdisciplinary subfield of anthropology with a long history of research on environmental health-related issues, especially those pertaining to human health within environments of risk, consequences of ecological degradation, and the way patterns of development and globalization impact environmental (and therefore human) health. In this article, the authors provide an introduction to the scope of medical anthropology research, its relevance to the field of environmental health, and the methods anthropologists use in their analyses. They conclude by elaborating on some of the key conceptual frameworks that guide current research and highlight topical areas in environmental health (broadly defined) where medical anthropology research is warranted.

negative: Factors affecting healthcare workers' compliance with social and behavioural infection control measures during emerging infectious disease outbreaks: Rapid evidence review. The 2019-2020 outbreak of novel coronavirus has raised concerns about nosocomial transmission; that is, transmission within healthcare settings. Research from previous outbreaks of emerging infectious diseases suggests a major cause of nosocomial transmission is healthcare professionals' poor compliance with recommended personal protective behaviours. This rapid evidence review explored existing literature on emerging infectious disease outbreaks to identify factors associated with compliance with social and behavioural infection control measures among healthcare staff. 56 papers were reviewed and several positive associations were found: Staff working in emergency or intensive care settings appeared more likely to comply with recommendations than those in other settings, and there was some evidence that contact with confirmed cases could improve compliance. There was some evidence that staff with higher levels of anxiety and higher concern about the risk of infection were more likely to comply with recommended behaviour, and that monitoring from superiors could improve compliance. Several negative associations were also found. Observed non-compliance of colleagues could hinder compliance. Staff identified many barriers to compliance related to personal protective equipment, including availability; perceived difficulty and effectiveness; inconvenience; discomfort; and a negative impact on patient care. There appeared to be many issues regarding the communication and ease of understanding of infection control guidance. Based on the results of this review we recommend provision of training and education tailored for different occupational roles within the healthcare setting; managerial staff 'leading by example'; ensuring adequate resources for infection control; and timely provision of practical evidence-based infection control guidelines.

negative: Detection of Influenza and Other Respiratory Viruses Carried Out in the Influenza Project – Monitoring Vaccine Effectiveness (I-MOVE) The project Influenza Vaccine Effectiveness-Monitoring (I-MOVE) is part of the European research carried out by the ECDC (European Center for Disease Prevention and Control), aimed at monitoring the effectiveness of vaccination in Europe during the growing incidence of flu and influenza-like illnesses in the coming epidemic seasons. Laboratory studies using molecular RT-PCR biology methods for detection of genetic material of influenza virus and other respiratory viruses were performed by Voivodeship Sanitary-Epidemiological Stations in Poland. The validation of the results of swabs taken from the nose and throat were carried out in the Department of Influenza Research, National Influenza Center in Warsaw. The study involved 210 samples from patients across Poland. Positive results were recorded for 72.4 % of the samples; influenza virus type A was detected in 43 and type B in 38 cases, whereas in 71 cases other respiratory viruses were detected, which included Human parainfluenza virus type 1–4; Human respiratory syncytial virus type A and B; Human coronavirus 229E/NL63, OC43; Human rhinovirus type A, B, and C; Human enterovirus; and Human adenovirus. The results show that although influenza viruses predominated in the 2010/2011 season in Poland, other flu-like viruses also abounded.

negative: The COVID-19 pandemic and research shutdown: staying safe and productive. The Coronavirus Disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has caused severe disease outcomes and widespread infections not seen in terms of its case fatality rate and global economic impact since the 1918-1919 Spanish flu; the latter leading to 675,000 deaths in the United States (US) (50 million worldwide).

negative: COVID‐19 and SARS: Differences and similarities

negative: Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic BACKGROUND: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. METHODOLOGY/PRINCIPAL FINDINGS: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16–4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. CONCLUSIONS: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public.

negative: Modeling the impact of human mobility and travel restrictions on the potential spread of SARS-CoV-2 in Taiwan Background: As COVID-19 continues to spread around the world, understanding how patterns of human mobility and connectivity affect outbreak dynamics, especially before outbreaks establish locally, is critical for informing response efforts. Methods: Here, in collaboration with Facebook Data for Good, we built metapopulation models that incorporate human movement data with the goals of identifying the high risk areas of disease spread and assessing the potential effects of local travel restrictions in Taiwan. We compared the impact of intracity vs. intercity travel restrictions on both the total number of infections and the speed of outbreak spread and developed an interactive application that allows users to vary inputs and assumptions. Findings: We found that intracity travel reductions have a higher impact on overall infection numbers than intercity travel reductions, while intercity travel reductions can narrow the scope of the outbreak and help target resources. We also identified the most highly connected areas that may serve as sources of importation during an outbreak. The timing, duration, and level of travel reduction together determine the impact of travel reductions on the number of infections, and multiple combinations of these can result in similar impact. Interpretation: In Taiwan, most cases to date were imported or linked to imported cases. To prepare for the potential spread within Taiwan, we utilized Facebook's aggregated and anonymized movement and colocation data to identify cities with higher risk of infection and regional importation. Both intracity and intercity movement affect outbreak dynamics, with the former having more of an impact on the total numbers of cases and the latter impacting geographic scope. These findings have important implications for guiding future policies for travel restrictions during outbreaks in Taiwan.

negative: Impact of 2009 pandemic influenza among Vietnamese children based on a population-based prospective surveillance from 2007 to 2011 BACKGROUND: Influenza virus is one of the major viral pathogens causing pediatric acute respiratory infection (ARI). The spread of pandemic influenza A (A(H1N1)pdm09) in 2009 around the globe had a huge impact on global health. OBJECTIVE: To investigate the impact of A(H1N1)pdm09 on pediatric ARI in Vietnam. STUDY DESIGN: An ongoing population-based prospective surveillance in central Vietnam was used. All children aged <15 years residing in Nha Trang city, enrolled to the ARI surveillance in Khanh Hoa General Hospital, from February 2007 through March 2011 were studied. Clinical data and nasopharyngeal swab samples were collected. Influenza A was detected and genotyped by multiplex polymerase chain reaction assays and sequencing. RESULTS: Among enrolled 2736 hospitalized ARI cases, 354 (13%) were positive for influenza A. Genotyping results revealed that seasonal H3N2 and H1N1 (sea-H1N1) viruses were cocirculating before A(H1N1)pdm09 appeared in July 2009. The A(H1N1)pdm09 replaced the sea-H1N1 after the pandemic. The majority of influenza A cases (90%) were aged <5 years with incidence rate of 537 (387–775) per 100 000 population. Annual incidence rates of hospitalized influenza cases for pre-, initial and post-pandemic periods among children aged <5 year were 474, 452, and 387 per 100 000, respectively. Children with A(H1N1)pdm09 were elder, visited the hospital earlier, less frequently had severe signs, and were less frequently associated with viral coinfection compared with seasonal influenza cases. CONCLUSIONS: The A(H1N1)pdm09 did not increase the influenza annual hospitalization incidence or disease severity compared with seasonal influenza among pediatric ARI cases in central Vietnam.

negative: Coronavirus leader‐RNA‐primed transcription: An alternative mechanism to RNA splicing Many viral and cellular mRNA species contain a leader sequence derived from a distant upstream site on the same gene by a process of RNA splicing. This process usually involves either nuclear functions or self‐splicing of RNA molecules. Coronavirus, a cytoplasmic RNA virus, unfolds yet another mechanism of joining RNA, which involves the use of a free leader RNA molecule. This molecule is synthesized and dissociates from the template RNA, and subsequently reassociates with the template RNA at down‐stream initiation sites of subgenomic mRNAs to serve as the primer for transcription. This leader‐primed transcriptional process thus generates viral mRNAs with a fused leader sequence. A similar mechanism might also operate in the mRNA transcription of African trypanosomes.

negative: How to shape research to advance global health.

negative: Association of IFITM3 rs12252 polymorphisms, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population BACKGROUND: IFITM3 has been suggested to be associated with infection in some ethnic groups. Diabetes and hypercholesterolemia are also important clinical conditions that can predispose individuals to infection. The aim of this study was to investigate the association of rs12252 C polymorphism, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population. METHODS: We conducted a case-control study, including 79 mild flu and 125 flu-negative individuals attending primary care centers of three provinces of Iran (i.e, Markazi, Semnan, and Zanjan). Pharyngeal swab specimens were collected from all participants, and were subjected to RNA and DNA extractions for Real-time PCR and PCR tests. All PCR products were then sequenced to find T/C polymorphisms in the rs12252 region. Data on demographic, anthropometric, and clinical variables were collected from participants’ medical records available in the primary care centers. The data was analyzed using DNASIS (v. 2.5) and Stata (v.11) software. RESULTS: All participants were of Fars ethnic background. The allele frequency for rs12252-C was found to be 9.49% among cases and 2.40% among controls. Carriers of the rs12252 C allele (CT + CC genotypes) showed 5.92 folds increase in the risk of mild flu comparing to the T allele homozygotes (P value: 0.007). We also found a significant positive association between rs12252 C allele heterozygote and mild flu (OR: 7.62, P value: 0.008), but not in C allele homozygote group (OR: 2.71, P value: 0.406). Similarly, we did not find a significant association between mild flu and BMI (OR: 1.06, P value: 0.087), diabetes (OR: 0.61, P value: 0.392), and hypercholesterolemia (OR: 0.50, P value: 0.393) in multivariable logistic regression. CONCLUSIONS: This is the first study evaluating the association between rs12252 polymorphisms, diabetes, hypercholesterolemia, and BMI and susceptibility to mild flu in an Iranian population. Our results suggest a significant positive association between mild flu and rs12252 C allele heterozygous and carriage. Future replication of the strong association observed here between rs12252 C allele carriage and mild flu might candidate this polymorphism as a genetic marker for early screening of susceptibility to mild flu. Lack of significant association between C allele homozygous and mild flu, observed in this study, might be the result of small sample size in this group. TRIAL REGISTRATION: IR.PII.REC.1395.3. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-017-0884-4) contains supplementary material, which is available to authorized users.

negative: Declining Public Health Protections within Autocratic Regimes: Impact on Global Public Health Security, Infectious Disease Outbreaks, Epidemics, and Pandemics Public health emergencies of international concern, in the form of infectious disease outbreaks, epidemics, and pandemics, represent an increasing risk to the world's population. Management requires coordinated responses, across many disciplines and nations, and the capacity to muster proper national and global public health education, infrastructure, and prevention measures. Unfortunately, increasing numbers of nations are ruled by autocratic regimes which have characteristically failed to adopt investments in public health infrastructure, education, and prevention measures to keep pace with population growth and density. Autocratic leaders have a direct impact on health security, a direct negative impact on health, and create adverse political and economic conditions that only complicate the crisis further. This is most evident in autocratic regimes where health protections have been seriously and purposely curtailed. All autocratic regimes define public health along economic and political imperatives that are similar across borders and cultures. Autocratic regimes are seriously handicapped by sociopathic narcissistic leaders who are incapable of understanding the health consequences of infectious diseases or the impact on their population. A cross section of autocratic nations currently experiencing the impact of COVID-19 (coronavirus disease 2019) are reviewed to demonstrate the manner where self-serving regimes fail to manage health crises and place the rest of the world at increasing risk. It is time to re-address the pre-SARS (severe acute respiratory syndrome) global agendas calling for stronger strategic capacity, legal authority, support, and institutional status under World Health Organization (WHO) leadership granted by an International Health Regulations Treaty. Treaties remain the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world."Honesty is worth a lot more than hope " The Economist, February 17, 2020.

negative: Chloroquine or Hydroxychloroquine for COVID-19: Is Cardiotoxicity a Concern? The SARS-Cov-2 viral pandemic causing COVID-19 disease begs for rapid and innovative treatments. In addition to flu-like respiratory symptoms, acute cardiac manifestations include cardiac injury, shock and arrhythmia. Several pharmacological therapies have been suggested including repurposing of existing drugs such as chloroquine and hydroxychloroquine, sometimes co-administered with azithromycin. Chloroquine and hydroxychloroquine were developed in the World War II era for treatment and prophylaxis of malaria, long before modern drug safety surveillance programs. Clinically they can prolong the QT interval to potentially initiate ventricular arrhythmias including torsades de pointes, and also cause QRS widening. Chloroquine interacts with multiple cardiac ion channels including the hERG potassium channel that is essential for normal electrical activity in the heart. A reduction in hERG channel potassium current is the principle cause of drug-induced long QT syndrome. Azithromycin also can cause modest QT interval prolongation, but not through potent hERG channel blockade, rather when used chronically through an increase in peak and late cardiac sodium current to cause potential loading of cardiomyocytes with sodium and calcium to produce calcium overload. How should we proceed with the use of chloroquine and hydroxychloroquine, potentially combined with azithromycin, for COVID-19 given that these agents bring some cardiac toxicity risk and their mechanisms for cardiac toxicity may not be the same? Is combining different and potentially additive mechanisms of cardiotoxicity wise? How great the risk is relative to the benefit in critically ill COVID-19 patients will need to await the outcome of ongoing, controlled clinical trials.

negative: Psychological symptoms of ordinary Chinese citizens based on SCL-90 during the level I emergency response to COVID-19 The World Health Organization (WHO) has declared that the Corona Virus (COVID-19) has become a global pandemic. This study aimed to investigate the psychological symptoms of ordinary Chinese citizens during the Level I Emergency Response throughout China. From January 31 to February 2 2020, an online questionnaire, Symptom Checklist 90 (SCL-90) was designed, and differences in GSI T-scores among subgroups were examined by ANOVA. Based on a cut-off point of the GSI T-scores of 63, the overall sample was divided into high and low-risk groups. of the 1,060 participants investigated in China, more than 70% of them have moderate and higher level of psychological symptoms specifically elevated scores for obsessive compulsion, interpersonal sensitivity, phobic anxiety, and psychoticism. There were no significant differences between males and females. Those who were of over 50 years old, had an undergraduate education and below, were divorced or widowed, and agricultural workers had significantly more symptoms. However, significantly more minors and medical staff were in the high-risk group. These results show that COVID-19 has a significant adverse socio-psychological influence on ordinary citizens. Therefore, governments should equip psychological health departments and pay attention to the people who are in high-risk groups, providing psychological interventions and assistance.

negative: Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. METHODS AND FINDINGS: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. CONCLUSIONS: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002- NCT01056354, FLU 003- NCT01056185.

negative: Viral Diversity of Microbats within the South West Botanical Province of Western Australia Bats are known reservoirs of a wide variety of viruses that rarely result in overt clinical disease in the bat host. However, anthropogenic influences on the landscape and climate can change species assemblages and interactions, as well as undermine host-resilience. The cumulative result is a disturbance of bat–pathogen dynamics, which facilitate spillover events to sympatric species, and may threaten bat communities already facing synergistic stressors through ecological change. Therefore, characterisation of viral pathogens in bat communities provides important basal information to monitor and predict the emergence of diseases relevant to conservation and public health. This study used targeted molecular techniques, serological assays and next generation sequencing to characterise adenoviruses, coronaviruses and paramyxoviruses from 11 species of insectivorous bats within the South West Botanical Province of Western Australia. Phylogenetic analysis indicated complex ecological interactions including virus–host associations, cross-species infections, and multiple viral strains circulating concurrently within selected bat populations. Additionally, we describe the entire coding sequences for five alphacoronaviruses (representing four putative new species), and one novel adenovirus. Results indicate that viral burden (both prevalence and richness) is not homogeneous among species, with Chalinolobus gouldii identified as a key epidemiological element within the studied communities.

negative: Overview of Covid-19; its prevention and management in the light of Unani medicine Abstract Since December 2019, a respiratory pandemic, named as coronavirus disease 2019 (Covid-19) caused by a new coronavirus named as SARS-CoV-2, has taken the world by storm. The symptoms are fever, malaise, and cough which resolve in a few days in most cases; but may progress to respiratory distress and organ failure. Transmission is through droplet infection or fomites, but other modes such as airborne transmission and oro-fecal transmission is also speculated. Research is underway to develop effective vaccines and medicines for the disease. In such a scenario, we present the measures described in Unani system of medicine for health protection during epidemics. Unani is a traditional system of medicine developed during the middle ages, which employs natural drugs of herbal, animal and mineral origin for treatment. In Unani medicine, during an epidemic, apart from isolation and quarantine, three measures are of utmost importance, (i) purification of surroundings using certain herbal drugs as fumigants or sprays, (ii) health promotion and immune-modulation, and (iii) use of health-protecting drugs and symptom-specific drugs. Drugs such as loban (Styrax benzoides W. G. Craib), sandroos (Hymenaea verrucosa Gaertn.) za'fran (Crocus sativus L.), vinegar etc. are prescribed in various forms. Scientific researches on these drugs reveal the presence of a number of pharmacologically active substances, which may provide a new insight into the management of infections and epidemics.

negative: A typology of beliefs and misperceptions about the influenza disease and vaccine among older adults in Singapore Access to the influenza vaccine pose little barriers in developed countries such as Singapore and vaccination against influenza is highly recommended for at-risk populations including older adults. However, vaccination rates are much lower than recommended despite the significant morbidity and mortality associated with the disease among this vulnerable population. Given timely goals to increase vaccine acceptance and uptake, we explored Singaporean older adults’ misperceptions about influenza disease and vaccine. Qualitative semi-structured interviews were conducted among 76 Singaporean adults aged 65 and above with no focus on a specific area in Singapore. Data were analyzed with grounded theory methods to understand participants’ attitudes, perceptions, and knowledge. We developed in vivo codes that reflect the verbiage used by participants and exhaustively catalogued themes through a constant comparison coding method. Focusing specifically on older adults’ misperceptions, seven main themes about influenza disease or vaccine emerged from our data analysis: familiarity with influenza, misperceptions about influenza, personal susceptibility to influenza, familiarity with the influenza vaccine, misperceptions about the influenza vaccine, misperceptions about influenza vaccine usage, and opinions about and barriers to influenza vaccine uptake. Notably, there is a lack of adequate knowledge and motivation in vaccinating against influenza among older adults in Singapore. Health communication needs to be more tailored toward older adults’ message processing systems and engage health professionals’ involvement in addressing the influenza disease and vaccine misperceptions identified in this study.

negative: 2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county, and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE)-mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics. Author Video: An author video summary of this article is available.

negative: COVID-19 and pets: When pandemic meets panic Abstract As the novel coronavirus outbreak spreads globally with devastating effects on human health, pets are also becoming unnecessary victims amidst the pandemic panic. Many have been reluctantly left home alone by owners who have been forced to temporarily evacuate their homes. And, although no evidence exists to indicate that they can either transmit the virus or develop its associated coronavirus disease 2019 (COVID-19), fear among the public that pets might play a role in spreading COVID-19 has resulted in pets being abandoned or even killed. This article outlines some of the ways in which the current pandemic has negatively impacted the welfare of pets. It also highlights the relationships between animal, human, and environmental health, as well as the importance of taking a collaborative transdisciplinary One Health approach to help prevent future COVID-19 outbreaks.

negative: MERS: emergence of a novel human coronavirus A novel coronavirus (CoV) that causes a severe lower respiratory tract infection in humans, emerged in the Middle East region in 2012. This virus, named Middle East respiratory syndrome (MERS)-CoV, is phylogenetically related to bat CoVs, but other animal species like dromedary camels may potentially act as intermediate hosts by spreading the virus to humans. Although human to human transmission has been demonstrated, analysis of human MERS clusters indicated that chains of transmission were not self-sustaining, especially when infection control was implemented. Thus, timely identification of new MERS cases followed by their quarantine, combined with measures to limit spread of the virus from the (intermediate) host to humans, may be crucial in controlling the outbreak of this emerging CoV.

negative: The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research BACKGROUND: During pandemics, health authorities may be uncertain about the spread and severity of the disease and the effectiveness and safety of available interventions. This was the case during the swine flu (H1N1) pandemic of 2009–2010, and governments were forced to make decisions despite these uncertainties. While many countries chose to implement wide scale vaccination programmes, few accomplished their vaccination goals. Many research studies aiming to explore barriers and facilitators to vaccine uptake have been conducted in the aftermath of the pandemic, including several qualitative studies. AIMS: 1. To explore public attitudes to the swine flu vaccine in different countries through a review of qualitative primary studies. 2. To describe and discuss the implications drawn by the primary study authors. METHODS: Systematic review of qualitative research studies, using a broadly comparative cross case-study approach. Study quality was appraised using an adaptation of the Critical Appraisal Skills Programme (CASP) quality assessment tool. RESULTS: The review indicates that the public had varying opinions about disease risk and prevalence and had concerns about vaccine safety. Most primary study authors concluded that participants were uninformed, and that more information about the disease and the vaccine would have led to an increase in vaccine uptake. We find these conclusions problematic. We suggest instead that people’s questions and concerns were legitimate given the uncertainties of the situation at the time and the fact that the authorities did not have the necessary information to convince the public. Our quality assessment of the included studies points to a lack of reflexivity and a lack of information about study context. We suggest that these study weaknesses are tied to primary study authors’ lack of acknowledgement of the uncertainties surrounding the disease and the vaccine. CONCLUSION: While primary study authors suggest that authorities could increase vaccine uptake through increased information, we suggest instead that health authorities should be more transparent in their information and decision-making processes in future pandemic situations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12913-016-1466-7) contains supplementary material, which is available to authorized users.

negative: Coronavirus-Pandemie  Erinnerungen an die Grippe-Epidemie von 1918 aus gynäkologisch-geburtshilflicher Sicht./ [Coronavirus pandemic-Memories of the flu epidemic from 1918 from a gynecological and obstetric perspective] From the medical reports on the flu epidemic in 1918, there is accordance with the present-day corona pandemic. The symptoms, course and outcome all seem to show parallels. Pregnant women in the last trimester are to be classified as being particularly vulnerable. Physicians in several disciplines, e.g. gynecology, general medicine and internal medicine are equally called upon to be particularly vigilant.

negative: Hospital Associated Respiratory Virus Infection in Children and Adults: It Does Not Just Occur During Cold and Flu Season Hospital-associated respiratory virus infections (HARVI) are an underappreciated source of morbidity and mortality. We examined HARVI incidence and clinical respiratory virus testing practices in a cohort of hospitalized patients with acute respiratory illness. HARVI were identified in patients of all ages, both during and outside of the influenza season.

negative: Characterization of respiratory infection viruses in hospitalized children from Naples province in Southern Italy Most acute respiratory infections (ARIs) in children are due to viral etiology, and represent an important cause of mortality and morbidity in children <5 years old in developing countries. The pathogens that cause ARIs vary geographically and by season, and viruses serve a major role. In the present study, the distribution of the seven respiratory viruses that are more prevalent in Southern European countries were retrospectively analyzed in a Southern Italy Hospital, that centralizes pediatric diseases from the Naples province. Viruses were categorized by a FilmArray Respiratory Panel, and demonstrated no substantial differences in sex, age and seasonal viruses distribution. However, all the investigated viruses had a higher detection rate in the surrounding municipalities than in the metropolitan area of Naples. In recent years, the association between air pollution and respiratory infections has become an increasing public health concern. The data in this study support this association in the surrounding areas of Naples extensively contaminated by environmental toxic agents. In these areas, characterization of the epidemiology of ARIs is required to implement a prevention and control program.

negative: COVID-19 and smoking: A systematic review of the evidence COVID-19 is a coronavirus outbreak that initially appeared in Wuhan, Hubei Province, China, in December 2019, but it has already evolved into a pandemic spreading rapidly worldwide(1,2). As of 18 March 2020, a total number of 194909 cases of COVID-19 have been reported, including 7876 deaths, the majority of which have been reported in China (3242) and Italy (2505)(3). However, as the pandemic is still unfortunately under progression, there are limited data with regard to the clinical characteristics of the patients as well as to their prognostic factors(4). Smoking, to date, has been assumed to be possibly associated with adverse disease prognosis, as extensive evidence has highlighted the negative impact of tobacco use on lung health and its causal association with a plethora of respiratory diseases(5). Smoking is also detrimental to the immune system and its responsiveness to infections, making smokers more vulnerable to infectious diseases(6). Previous studies have shown that smokers are twice more likely than non-smokers to contract influenza and have more severe symptoms, while smokers were also noted to have higher mortality in the previous MERS-CoV outbreak(7,8). Given the gap in the evidence, we conducted a systematic review of studies on COVID-19 that included information on patients’ smoking status to evaluate the association between smoking and COVID-19 outcomes including the severity of the disease, the need for mechanical ventilation, the need for intensive care unit (ICU) hospitalization and death. The literature search was conducted on 17 March 2020, using two databases (PubMed, ScienceDirect), with the search terms: [‘smoking’ OR ‘tobacco’ OR ‘risk factors’ OR ‘smoker*’] AND [‘COVID-19’ OR ‘COVID 19’ OR ‘novel coronavirus’ OR ‘sars cov-2’ OR ‘sars cov 2’] and included studies published in 2019 and 2020. Further inclusion criteria were that the studies were in English and referred to humans. We also searched the reference lists of the studies included. A total of 71 studies were retrieved through the search, of which 66 were excluded after full-text screening, leaving five studies that were included. All of the studies were conducted in China, four in Wuhan and one across provinces in mainland China. The populations in all studies were patients with COVID-19, and the sample size ranged from 41 to 1099 patients. With regard to the study design, retrospective and prospective methods were used, and the timeframe of all five studies covered the first two months of the COVID-19 pandemic (December 2019, January 2020). Specifically, Zhou et al.(9) studied the epidemiological characteristics of 191 individuals infected with COVID-19, without, however, reporting in more detail the mortality risk factors and the clinical outcomes of the disease. Among the 191 patients, there were 54 deaths, while 137 survived. Among those that died, 9% were current smokers compared to 4% among those that survived, with no statistically significant difference between the smoking rates of survivors and non-survivors (p=0.21) with regard to mortality from COVID-19. Similarly, Zhang et al.(10) presented clinical characteristics of 140 patients with COVID-19. The results showed that among severe patients (n=58), 3.4% were current smokers and 6.9% were former smokers, in contrast to non-severe patients (n=82) among which 0% were current smokers and 3.7% were former smokers , leading to an OR of 2.23; (95% CI: 0.65–7.63; p=0.2). Huang et al.(11) studied the epidemiological characteristics of COVID-19 among 41 patients. In this study, none of those who needed to be admitted to an ICU (n=13) was a current smoker. In contrast, three patients from the non-ICU group were current smokers, with no statistically significant difference between the two groups of patients (p=0.31), albeit the small sample size of the study. The largest study population of 1099 patients with COVID-19 was provided by Guan et al.(12) from multiple regions of mainland China. Descriptive results on the smoking status of patients were provided for the 1099 patients, of which 173 had severe symptoms, and 926 had non-severe symptoms. Among the patients with severe symptoms, 16.9% were current smokers and 5.2% were former smokers, in contrast to patients with non-severe symptoms where 11.8% were current smokers and 1.3% were former smokers. Additionally, in the group of patients that either needed mechanical ventilation, admission to an ICU or died, 25.5% were current smokers and 7.6% were former smokers. In contrast, in the group of patients that did not have these adverse outcomes, only 11.8% were current smokers and 1.6% were former smokers. No statistical analysis for evaluating the association between the severity of the disease outcome and smoking status was conducted in that study. Finally, Liu et al.(13) found among their population of 78 patients with COVID-19 that the adverse outcome group had a significantly higher proportion of patients with a history of smoking (27.3%) than the group that showed improvement or stabilization (3.0%), with this difference statistically significant at the p=0.018 level. In their multivariate logistic regression analysis, the history of smoking was a risk factor of disease progression (OR=14.28; 95% CI: 1.58–25.00; p= 0.018). We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed severity, there were higher percentages of current and former smokers among patients that needed ICU support, mechanical ventilation or who had died, and a higher percentage of smokers among the severe cases(12). However, from their published data we can calculate that the smokers were 1.4 times more likely (RR=1.4, 95% CI: 0.98–2.00) to have severe symptoms of COVID-19 and approximately 2.4 times more likely to be admitted to an ICU, need mechanical ventilation or die compared to non-smokers (RR=2.4, 95% CI: 1.43–4.04). In conclusion, although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19.

negative: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19? INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.

negative: Respiratory Hygiene and Cough Etiquette Respiratory infections are a leading cause of illness, morbidity, and mortality around the globe. Easily transmitted between people, respiratory pathogens are a leading cause of widespread illness but can be prevented. With the use of standard precautions, appropriate respiratory and hand hygiene, and appropriate patient precautions at the onset of symptoms, respiratory infections can be managed and maintained. There are several key pathogens that contribute to the burden of respiratory disease across the globe, among them are Mycobacterium tuberculosis and Haemophilus influenzae. Some respiratory infections are self-limiting and require symptomatic treatment, while some require specific treatments and antibiotics. This chapter will review protocols to limit the spread of respiratory infections, respiratory hygiene methods, as well as common and virulent respiratory infections and methods of management and treatment.

negative: Influenza vaccination in the COVID-19 era Abstract Influenza spreads globally annually with significant paediatric and adult attack rates and considerable morbidity, mortality and the exacerbation of extant chronic disease. In the northern and southern hemispheres, outbreaks occur mainly in the respective winter seasons. Influenza vaccination is available but only partially effective. In the absence of a vaccine, in winter, novel coronavirus COVID-19 will also circulate in parallel with seasonal influenza. Thus far it appears that with the current strains of these two viruses, the clinical outcome of co-infection is not significantly worse than infection with COVID-19 alone. However, several strains of influenza circulate, including strains still to come. Similarly, COVID-19 has several strains, with probably more to come. This paper discusses these issues and estimates ideal minimum influenza vaccination coverage based on an estimated influenza Basic Reproduction Number (R0) of 0.9–2.1 so as to obtain herd immunity or approach it. There is a strong argument for attempting near universal population coverage with the annual influenza vaccine leading up to next winter.

negative: Per-Ventricular Insertion of Melody Valve-in-Valve in the Neoaortic Position in a Single-Ventricle Patient. Percutaneous therapies for congenital heart disease have been evolving rapidly despite limited investment from industry. The Melody transcatheter pulmonary valve (Medtronic, Inc, Minneapolis, MN USA) replacement therapy represents an important advancement in this arena. It has been approved in the United States for use in the pulmonary position, on a Humanitarian Device Exemption status. Off-label use of the Melody transcatheter pulmonary valve has extended to the mitral, pulmonary, and aortic valves, especially in previously implanted valves with prosthetic valve degeneration. The single-ventricle patient poses additional challenges. However, there exists one report in the English literature of a patient undergoing Melody transcatheter neoaortic valve replacement after the patient developed severe neoaortic regurgitation after Fontan palliation. Here, we describe a patient with hypoplastic left heart syndrome, palliated with a Norwood modified Blalock-Taussig shunt, with a progressively regurgitant quadricusp neoaortic valve who underwent bioprosthetic valve replacement. There was early prosthetic valve degeneration after a year of bioprosthesis implantation. As he was declined for transplantation, he underwent successful per-ventricular Melody valve-in-valve replacement.

negative: Nosocomial Tuberculosis in India Most high-income countries implement tuberculosis (TB) infection control programs to reduce the risk for nosocomial transmission. However, such control programs are not routinely implemented in India, the country that accounts for the largest number of TB cases in the world. Despite the high prevalence of TB in India and the expected high probability of nosocomial transmission, little is known about nosocomial and occupational TB there. The few available studies suggest that nosocomial TB may be a problem. We review the available data on this topic, describe factors that may facilitate nosocomial transmission in Indian healthcare settings, and consider the feasibility and applicability of various recommended infection control interventions in these settings. Finally, we outline the critical information needed to effectively address the problem of nosocomial transmission of TB in India.

negative: Serial interval of novel coronavirus (COVID-19) infections Abstract Objective To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. Methods We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n = 28) and a subset of pairs with highest certainty in reporting (n = 18). In addition, we adjust for right truncation of the data as the epidemic is still in its growth phase. Results Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9). Conclusions The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias.

negative: Hajj-associated infections Abstract Background The Hajj is the largest annual mass gathering event in the world, thus favoring the transmission of various infections: 183 different nationalities, high temperatures, coincidence with the start of the flu season in the Northern hemisphere, a long barefoot walk, tent-type accommodation, communal toilet facilities, absence of food control, and sharing of razors. Infections are the first cause of hospital admission, which often occurs in the home country of pilgrims. Methods Literature review on PubMed from 1952 to November 2015 on the epidemiology and prevention of infections contracted during the Hajj, using the keywords “Hajj” and “infections”. Results Respiratory tract infections, ENT infections, influenza, pyogenic pneumonia, whooping cough, and tuberculosis are most frequently observed during the Hajj. Outbreaks of meningococcal meningitis have been reported in pilgrims and their contacts. Waterborne infections such as gastroenteritis and hepatitis A are common, despite the improvement of health conditions. Pyoderma and furuncles are also frequently observed. Recently, dengue fever, Alkhumra hemorrhagic fever, and Rift Valley fever have emerged but no case of MERS-coronavirus, appeared in Saudi Arabia in 2012, have yet been observed during the 2012–2014 Hajj. Conclusion Prevention is based on compulsory meningococcal vaccination, vaccination against seasonal influenza and pneumococcal infections for pilgrims at high risk of contracting the infection, and on vaccination against hepatitis A. Updating immunization for diphtheria/tetanus/poliomyelitis/pertussis and measles/mumps is also crucial and pilgrims must comply with hygiene precautions.

negative: Pathologic Findings in Novel Influenza A (H1N1) Virus (“Swine Flu”) Infection: Contrasting Clinical Manifestations and Lung Pathology in Two Fatal Cases Although novel influenza A (H1N1) virus infection has assumed pandemic proportions, there are few reports of the pathologic findings. Herein we describe the pathologic findings of novel influenza A (H1N1) infection based on findings in 2 autopsy cases. The first patient, a 36-year-old man, had flu-like symptoms; oseltamivir (Tamiflu) therapy was started 8 days after onset of symptoms, and he died on day 15 of his illness. At autopsy, the main finding was diffuse alveolar damage with extensive fresh intra-alveolar hemorrhage. The second patient, a 46-year-old woman with alcoholism, was found unresponsive in a basement and brought to the hospital intoxicated and confused. Her condition deteriorated rapidly, and she died 4 days after admission. The main autopsy finding was acute bronchopneumonia with gram-positive cocci, intermixed with diffuse alveolar damage. The pathologic findings in these contrasting cases of novel influenza A (H1N1) infection are similar to those previously described for seasonal influenza. The main pathologic abnormality in fatal cases is diffuse alveolar damage, but it may be overshadowed by an acute bacterial bronchopneumonia.

negative: Achievements and highlights for Infection, Disease and Health

negative: Emerging Influenza D Virus Threat: What We Know so Far! Influenza viruses, since time immemorial, have been the major respiratory pathogen known to infect a wide variety of animals, birds and reptiles with established lineages. They belong to the family Orthomyxoviridae and cause acute respiratory illness often during local outbreaks or seasonal epidemics and occasionally during pandemics. Recent studies have identified a new genus within the Orthomyxoviridae family. This newly identified pathogen, D/swine/Oklahoma/1334/2011 (D/OK), first identified in pigs with influenza-like illness was classified as the influenza D virus (IDV) which is distantly related to the previously characterized human influenza C virus. Several other back-to-back studies soon suggested cattle as the natural reservoir and possible involvement of IDV in the bovine respiratory disease complex was established. Not much is known about its likelihood to cause disease in humans, but it definitely poses a potential threat as an emerging pathogen in cattle-workers. Here, we review the evolution, epidemiology, virology and pathobiology of influenza D virus and the possibility of transmission among various hosts and potential to cause human disease.

negative: The Etiological Role of Common Respiratory Viruses in Acute Respiratory Infections in Older Adults: A Systematic Review and Meta-analysis Acute respiratory tract infections (ARI) constitute a substantial disease burden in adults and elderly individuals. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged ≥65 years. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017 that investigated the viral profile of older adults with and those without ARI. We then computed a pooled odds ratio (OR) with a 95% confidence interval and virus-specific attributable fraction among the exposed (AFE) for 8 common viruses: respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence of possible causal attribution for RSV (OR, 8.5 [95% CI, 3.9–18.5]; AFE, 88%), Flu (OR, 8.3 [95% CI, 4.4–15.9]; AFE, 88%), PIV (OR, not available; AFE, approximately 100%), HMPV (OR, 9.8 [95% CI, 2.3–41.0]; AFE, 90%), AdV (OR, not available; AFE, approximately 100%), RV (OR, 7.1 [95% CI, 3.7–13.6]; AFE, 86%) and CoV (OR, 2.8 [95% CI, 2.0–4.1]; AFE, 65%) in older adults presenting with ARI, compared with those without respiratory symptoms (ie, asymptomatic individuals) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV, and CoV as important causes of ARI in older adults and provides quantitative estimates of the absolute proportion of virus-associated ARI cases to which a viral cause can be attributed. Disease burden estimates should take into account the appropriate AFE estimates (for older adults) that we report.

negative: Answering the initial 20 questions on COVID-19 (January-February 2020)

negative: Successful healthcare delivery using ambulatory hospitals—past, present and future

negative: Novel human coronavirus (SARS-CoV-2): A lesson from animal coronaviruses Abstract The recent pandemic caused by the novel human coronavirus, referrred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not only is having a great impact on the health care systems and economies in all continents but it is also causing radical changes of common habits and life styles. The novel coronavirus (CoV) recognises, with high probability, a zoonotic origin but the role of animals in the SARS-CoV-2 epidemiology is still largely unknown. However, CoVs have been known in animals since several decades, so that veterinary coronavirologists have a great expertise on how to face CoV infections in animals, which could represent a model for SARS-CoV-2 infection in humans. In the present paper, we provide an up-to-date review of the literature currently available on animal CoVs, focusing on the molecular mechanisms that are responsible for the emergence of novel CoV strains with different antigenic, biologic and/or pathogenetic features. A full comprehension of the mechanisms driving the evolution of animal CoVs will help better understand the emergence, spreading, and evolution of SARS-CoV-2.

negative: Transnational Quarantine Rhetorics: Public Mobilization in SARS and in H1N1 Flu This essay examines how Chinese governments, local communities, and overseas Chinese in North America responded to the perceived health risks of Severe Acute Respiratory Syndrome (SARS) and H1N1 flu through the use of public and participatory rhetoric about risk and quarantines. Focusing on modes of security and quarantine practices, I examine how globalization and the social crises surrounding SARS and H1N1 flu operated to regulate differently certain bodies and areas. I identify three types of quarantines (mandatory, voluntary, and coerced) and conduct a transnational comparative analysis to investigate the relationships among quarantines, rhetoric, and public communication. I argue that health authorities must openly acknowledge the legitimacy of public input and actively seek public support regarding health crises. Only by collaborating with concerned communities and citizens and by providing careful guidance for public participation can health institutions ensure the efficacy of quarantine orders during emerging epidemics.

negative: The impact of covid-19 on rehabilitation services and activities. Letter to the editor in response to official document of SIMFER

negative: Direct Measurement of Rates of Asymptomatic Infection and Clinical Care-Seeking for Seasonal Coronavirus The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus. We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms. These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV.

negative: Integrated, multi-cohort analysis identifies conserved transcriptional signatures across multiple respiratory viruses Respiratory viral infections are a significant burden to healthcare worldwide. Many whole genome expression profiles have identified different respiratory viral infection signatures, but these have not translated to clinical practice. Here, we performed two integrated, multi-cohort analyses of publicly available transcriptional data of viral infections. First, we identified a common host signature across different respiratory viral infections that could distinguish (a) individuals with viral infections from healthy controls and from those with bacterial infections, and (b) symptomatic from asymptomatic subjects prior to symptom onset in challenge studies. Second, we identified an influenza-specific host response signature that (a) could distinguish influenza-infected samples from those with bacterial and other respiratory viral infections, (b) was a diagnostic and prognostic marker in influenza-pneumonia patients and influenza challenge studies, and (c) was predictive of response to influenza vaccine. Our results have applications in the diagnosis, prognosis, and identification of drug targets in viral infections.

negative: The Role of Animal Models In Influenza Vaccine Research A major challenge for research on influenza vaccines is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response to influenza infection in humans. Vaccines for seasonal influenza have been available for decades and there is a wealth of data available on the immune response to these vaccines in humans, with well-established correlates of protection for inactivated influenza virus vaccines. Many of the seminal studies on vaccines for epidemic influenza have been conducted in human subjects. Studies in humans are performed less frequently now than they were in the past. Therefore, as the quest for improved influenza vaccines continues, it is important to consider the use of animal models for the evaluation of influenza vaccines, and a major challenge is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response to influenza infection in humans. The emergence of highly pathogenic H5N1 avian influenza (AI) viruses and the threat of a pandemic caused by AI viruses of this or another subtype has resulted in a resurgence of interest in influenza vaccine research. The development of vaccines for pandemic influenza presents a unique set of obstacles, not the least of which is that the demonstration of efficacy in humans is not possible. As the correlates of protection from pandemic influenza are not known, we rely on extrapolation of the lessons from seasonal influenza vaccines and on data from the evaluation of pandemic influenza vaccines in animal models to guide our decisions on vaccines for use in humans. The features and contributions of commonly used animal models for influenza vaccine research are discussed. The recent emergence of the pandemic 2009 H1N1 influenza virus underscores the unpredictable nature of influenza viruses and the importance of pandemic preparedness.

negative: Detection of a group 2 coronavirus in dogs with canine infectious respiratory disease Abstract An investigation into the causes of canine infectious respiratory disease was carried out in a large rehoming kennel. Tissue samples taken from the respiratory tract of diseased dogs were tested for the presence of coronaviruses using RT–PCR with conserved primers for the polymerase gene. Sequence analysis of four positive samples showed the presence of a coronavirus with high similarity to both bovine and human coronavirus (strain OC43) in their polymerase and spike genes, whereas there was a low similarity to comparable genes in the enteric canine coronavirus. This canine respiratory coronavirus (CRCV) was detected by RT–PCR in 32/119 tracheal and 20/119 lung samples, with the highest prevalence being detected in dogs with mild clinical symptoms. Serological analysis showed that the presence of antibodies against CRCV on the day of entry into the kennel decreased the risk of developing respiratory disease.

negative: COVID-19, SARS and MERS: A neurological perspective Abstract Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS, MERS and COVID-19. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.

negative: [Severe acute respiratory syndrome and avian flu]. Severe acute respiratoru syndrome (SARS) is a new disease that caused large ourbreaks in several countries in the first half of 2003, resulting in infection in more than 8.000 people and more than 900 deaths. The disease originated in southern China and a novel coronavirus (SARS CoV) has been implicated as the causative organism. We present an overview of the etiology, clinical presentation and diagnosis, based on the current state of knowledge derived from published studies and our experience in the National Microbiology Centre. Influenza is a zoonosis. This appreciation of influenza ecologyfacilitated recognition of the H5N1 'bird flu' incident in Hong Kong in 1997 in what was considered to be an incipient pandemic situation, the chicken being the source of virus for humans and. The current outbreak of avian influenza in South East Asia has resulted in a small number of human deaths. These findings highlight the importance of systematic virus surveillance of domestic poultry in recognizing changes in virus occurrence, host range and pathogenicity as signals at the avian level that could presage a pandemic.

negative: Novel coronavirus disease (COVID-19): a pandemic (epidemiology, pathogenesis and potential therapeutics) The coronavirus disease (COVID-19) is highly pathogenic viral infection caused by SARS-CoV-2. Currently, COVID-19 has caused global health concern. It is assumed that COVID-19 has zoonotic origin based on the large number of infected people who were exposed to the wet market in Wuhan City, China. The phylogenetic analysis has revealed that SARS-CoV-2 has significant sequence similarity with severe acute respiratory syndrome-like (SARS-like) bat viruses, thus bats could be primary possible reservoir. The intermediate host and there subsequent transfer is not known yet, although human to human transfer is widely confirmed. The transmission of COVID-19 infection from one person to another resulted in the isolation of patients who were subsequently given a variety of treatments. To monitor the current outbreak, robust steps have been taken around the globe to reduce the transmission of COVID-19 infection particularly banning international and domestic flights, inducting lockdowns in vulnerable areas, social distancing etc. No clinically approved antiviral drug or vaccine against COVID-19 is reported yet. However, in clinical trials, few broad-spectrum antiviral drugs were evaluated against COVID-19 infection which resulted in clinical recovery. In this article emergence and pathogenicity of COVID-19 infection along with potential therapeutic strategies are analyzed to combat the COVID-19 pandemic.

negative: Key predictors of attending hospital with COVID19: An association study from the COVID Symptom Tracker App in 2,618,948 individuals Objectives: We aimed to identify key demographic risk factors for hospital attendance with COVID-19 infection. Design: Community survey Setting: The COVID Symptom Tracker mobile application co-developed by physicians and scientists at Kings College London, Massachusetts General Hospital, Boston and Zoe Global Limited was launched in the UK and US on 24th and 29th March 2020 respectively. It captured self-reported information related to COVID-19 symptoms and testing. Participants: 2,618,948 users of the COVID Symptom Tracker App. UK (95.7%) and US (4.3%) population. Data cut-off for this analysis was 21st April 2020. Main outcome measures: Visit to hospital and for those who attended hospital, the need for respiratory support in three subgroups (i) self-reported COVID-19 infection with classical symptoms (SR-COVID-19), (ii) self-reported positive COVID-19 test results (T-COVID-19), and (iii) imputed/predicted COVID-19 infection based on symptomatology (I-COVID-19). Multivariate logistic regressions for each outcome and each subgroup were adjusted for age and gender, with sensitivity analyses adjusted for comorbidities. Classical symptoms were defined as high fever and persistent cough for several days. Results: Older age and all comorbidities tested were found to be associated with increased odds of requiring hospital care for COVID-19. Obesity (BMI >30) predicted hospital care in all models, with odds ratios (OR) varying from 1.20 [1.11; 1.31] to 1.40 [1.23; 1.60] across population groups. Pre-existing lung disease and diabetes were consistently found to be associated with hospital visit with a maximum OR of 1.79 [1.64,1.95] and 1.72 [1.27; 2.31]) respectively. Findings were similar when assessing the need for respiratory support, for which age and male gender played an additional role. Conclusions: Being older, obese, diabetic or suffering from pre-existing lung, heart or renal disease placed participants at increased risk of visiting hospital with COVID-19. It is of utmost importance for governments and the scientific and medical communities to work together to find evidence-based means of protecting those deemed most vulnerable from COVID-19. Trial registration: The App Ethics have been approved by KCL ethics Committee REMAS ID 18210, review reference LRS-19/20-18210

negative: Rapid identification of imported influenza viruses at Xiamen International Airport via an active surveillance program Abstract Objectives The cross-border transmission of infectious diseases is a worldwide public health issue. Current border screening measures are insufficiently sensitive. The study objectives were to describe the epidemiologic pattern of influenza infection among incoming travellers at Xiamen International Airport during nonpandemic periods and to assess the performance of a rapid influenza diagnostic test in border screening. Methods Between May 2015 and May 2016, travellers with influenza-like illnesses entering China at Xiamen International Airport were screened with a rapid test, Flu Dot-ELISA, and the collected specimens were further subjected to virus isolation and phylogenetic analysis. Results Of the 1 540 076 incoming travellers, 1224 cases of influenza-like illness were identified; 261 tested positive in the rapid test, and 176 were confirmed to be influenza through virus culture. The sensitivity and specificity of the rapid test were demonstrated to be 96.6% (170/176) and 91.3% (957/1048), respectively, and the positive predictive and negative predictive values were 65.1% (170/261) and 99.4% (957/963), respectively. The epidemiologic study indicated that H3N2 and (H1N1)pdm09 were dominant in 2015 and 2016, respectively. In 2016, an increased number of influenza B isolates and cocirculation of both Victoria and Yamagata lineage influenza B viruses were observed, and mismatches between circulating influenza A(H1N1)pdm09 and influenza B Victoria lineage strains and vaccine strains also occurred. Conclusions We demonstrated the suitability and value of a high-sensitivity rapid influenza test in border screening and highlighted the importance of incoming travellers as a source of imported infectious diseases.

negative: Comparison of the Panther Fusion and Allplex assays for the detection of respiratory viruses in clinical samples Respiratory viral infections are the most frequent clinical syndrome affecting both children and adults, and early detection is fundamental to avoid infection-related risks and reduce the healthcare costs incurred by unnecessary antibiotic treatments. In this study, performance characteristics of two commercial methods, the Panther Fusion® assay (Hologic Inc., San Diego, CA, USA) were compared to Allplex(™) respiratory panels (Seegene, Seoul, South Korea) for the detection of influenza A (Flu A), influenza B (Flu B), respiratory syncytial virus (RSV), parainfluenza virus (PIV), human metapneumovirus (hMPV), rhinovirus (RV) and adenovirus (AdV) targets. A total of 865 specimens collected prospectively and retrospectively were included, and discordant results were further examined using another commercial product, R-GENE(™) respiratory kits (bioMérieux, Marcy l’Etoile, France). There was high agreement between both methods, with 98.6% concordance and a kappa (k) value of 0.9 (95% CI: 0.89–0.92). A specific analysis of both methods for each viral agent demonstrated comparable sensitivity and specificity, both ranging from 0.83 to 1 with good predictive values for the prospective part of the study. Good agreement between both methods was also found for the κ values obtained (ranging from 97.55% to 98.9%), with the lowest for hMPV (k = 0.83, 95% CI: 0.75–0.91) and RV (k = 0.73, 95% CI: 0.65–0.81). Amplification efficiency, measured according to the value of the cycle threshold (C(t)) obtained in each of the amplifications in both tests, was significantly better with Panther Fusion for Flu A, Flu B, hMPV and RV. Regarding discordant results, R-GENE showed higher agreement with Panther Fusion-positive specimens (negative for Allplex; n = 28/71, 34.9%) than with Allplex-positive samples (negative for Panther Fusion; n = 7/49, 14.3%). In summary, Panther Fusion proved to be a more efficient fully-automated methodology, requiring shorter hands-on and turnaround times than Allplex.

negative: Rapid clinical diagnosis in fatal swine influenza (H1N1) pneumonia in an adult with negative rapid influenza diagnostic tests (RIDTs): Diagnostic swine influenza triad Background The “herald wave” of the H1N1 pandemic spread from Mexico to the United States in spring 2009. Initially, the epicenter of H1N1 in the United States was in the New York area. Our hospital, like others, was inundated with large numbers of patients who presented at the Emergency Department (ED) with influenza-like illnesses (ILIs) for swine influenza testing and evaluation. Methods The Winthrop-University Hospital ED used rapid influenza (QuickVue A/B) tests to screen for H1N1 infection. Patients who were rapid influenza A test-positive were also reverse transcription-polymerase chain reaction (RT-PCR) positive for H1N1. In our ED, 30% of patients with ILIs and possible H1N1 pneumonia had negative rapid influenza A screening tests. Because H1N1 RT-PCR testing was restricted, there was no laboratory test to confirm or rule out H1N1. Other rapid influenza diagnostic tests (RIDTs), e.g., the respiratory fluorescent antibody (FA) viral panel test, were used to identify H1N1 patients with negative RIDTs. Results Unfortunately, there was not a good correlation between RIDT results and RT-PCR results. There was a critical need to develop a clinical syndromic approach for diagnosing hospitalized adults with probable H1N1 pneumonia with negative RIDTs. Early in the pandemic, the Winthrop-University Hospital Infectious Disease Division developed a diagnostic weighted point score system to diagnose H1N1 pneumonia clinically in RIDT-negative adults. The point score system worked well, but was time-consuming. As the “herald wave” of the pandemic progressed, our ED staff needed a rapid, simplified method to diagnose probable H1N1 pneumonia in hospitalized adults with negative RIDTs. A rapid and simplified diagnosis was based on the diagnostic weighted point score system, which we simplified into a triad of key, nonspecific laboratory indicators. In adults hospitalized with an ILI, a fever >102°F with severe myalgias, and a chest x-ray without focal segmental/lobar infiltrates, the presence of three indicators, i.e., otherwise unexplained relative lymphopenia, elevated serum transaminases, and an elevated creatinine phosphokinase, constituted the diagnostic swine influenza triad. The Infectious Disease Division's diagnostic swine flu triad was used effectively as the pandemic progressed, and was not only useful in correctly diagnosing probable H1N1 pneumonia in hospitalized adults with negative RIDTs, but was also in ruling out mimics of swine influenza, e.g., exacerbations of chronic bronchitis, asthma, or congestive heart failure, as well as bacterial community-acquired pneumonias (CAPs), e.g., legionnaire's disease. Conclusion Clinicians can use the Winthrop-University Hospital Infectious Disease Division's Diagnostic swine influenza triad to make a rapid clinical diagnosis of probable H1N1 pneumonia in hospitalized adult patients with negative RIDTs.

negative: The effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong, 2009–2013 Abstract Background Influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. There are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions. Methods We conducted a test-negative year-round study between October 2009 and September 2013, recruiting children 6months to 17years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Cases were tested for influenza A and B and conditional logistic regression was used to estimate vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive versus negative for influenza, adjusting for age and sex and matching by calendar week of recruitment. Results Overall vaccine effectiveness against hospitalization with laboratory-confirmed influenza A and B was estimated to be 61.7% (95% CI: 43.0%, 74.2%). The estimated vaccine effectiveness against A(H3N2) was 36.6% (95% CI: −25.5%, 67.9%) compared to 71.5% (95% CI: 39.4%, 86.6%) for A(H1N1)pdm09 and 68.8% (95% CI: 41.6%, 83.3%) for B. Conclusions Vaccine effectiveness against hospitalization in children varied from year to year, but was moderate to high overall even in an area with influenza activity throughout the year.

negative: Development of a risk assessment tool for contact tracing people after contact with infectious patients while travelling by bus or other public ground transport: a Delphi consensus approach BACKGROUND: Tracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases. However, criteria to decide when to conduct contact tracing are not well established. We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered. METHODS: Relevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations. We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport. We used the Delphi method with an international expert panel to position the values of criteria on the respective scales. RESULTS: The study led to the development of the ‘Contact Tracing-Risk Assessment Profile’ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria. This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport. DISCUSSION: The systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing. New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned.

negative: The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes BACKGROUND: Existing standard non-molecular diagnostic methods such as viral culture and immunofluorescent (DFA) are time-consuming, labor intensive or limited sensitivity. Several multiplex molecular assays are costly. Therefore, there is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. METHODS: A GeXP-based multiplex RT-PCR assay (GeXP assay) was developed to detect simultaneously sixteen different respiratory virus types/subtypes. Seventeen sets of chimeric primers were used to initiate the RT-PCR, and one pair of universal primers was used for the subsequent cycles of the RT-PCR. The specificity of the GeXP assay was examined with positive controls for each virus type/subtype. The sensitivity was evaluated by performing the assay on serial ten-fold dilutions of in vitro-transcribed RNA of all RNA viruses and the plasmids containing the Adv and HBoV target sequence. GeXP assay was further evaluated using 126 clinical specimens and compared with Luminex xTAG RVP Fast assay. RESULTS: The GeXP assay achieved a sensitivity of 20–200 copies for a single virus and 1000 copies when all of the 16 pre-mixed viral targets were present. Analyses of 126 clinical specimens using the GeXP assay demonstrated that GeXP assay and the RVP Fast assay were in complete agreement for 109/126 (88.51%) of the specimens. GeXP assay was more sensitive than the RVP Fast assay for the detection of HRV and PIV3, and slightly less sensitive for the detection of HMPV, Adv, RSVB and HBoV. The whole process of the GeXP assay for the detection of 12 samples was completed within 2.5 hours. CONCLUSIONS: In conclusion, the GeXP assay is a rapid, cost-effective, sensitive, specific and high throughput method for the detection of respiratory virus infections.

negative: The TVBG-SEIR spline model for analysis of COVID-19 spread, and a Tool for prediction scenarios Mathematical models are traditionally used to analyze the long-term global evolution of epidemics, to determine the potential and severity of an outbreak, and to provide critical information for identifying the type of disease interventions and intensity. One of the widely used mathematical models of long-term spreading of epidemics are the so-called deterministic compartmental models (SIR/SEIR type models). One of the main purposes of applying such models is to assess how the expensive restriction measures imposed by the authorities (home and social isolation/quarantine, travel restrictions, etc.) can effectively reduce the control reproduction number of the disease and its transmission risk. However the classical SIR/SEIR models have been primarily studied in what may be called stationary case, where the main parameters, the Transmission rate Beta (reflecting the virus spread by infected individuals) and the Removed rate Gamma (reflecting the hospitalization/isolation measures) remain constant during the whole period of interest. Hence, it is important to extend the classical SIR/SEIR models by creating new ansatzes for the dynamics of the transmission rates Beta(t) (which we will call further just Beta) and removed rates Gamma(t) (which we will call further just Gamma). The main purpose of the present research is to introduce a spline-based SEIR model with Time-varying Beta and Gamma parameters, or abbreviated TVBG-SEIR model, which is used to estimate the practical implications of the public health interventions and measures. We have designed a Tool based on the TVBG-SEIR model, which may be used as a Decision Support Tool to assist the health decision- and policy-makers in creating predictive scenarios.

negative: Emerging Viral Infections Emerging viral pathogens are a major cause of severe infections that constitute serious complications in patients with hematological disorders. During the last decade, a large number of viruses were discovered using optimized molecular techniques and systematic screening approaches. Most of the newly detected viruses affect the respiratory tract, causing common colds and also, especially in high-risk patients, life-threatening events. On the other hand, a substantial proportion of patients are reinfected by old viruses that were previously described only rarely or not at all in cancer patients. This chapter focuses on both emerging viruses and reemerging viral infections that affect patients with hematological malignancies.

negative: Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China Human coronaviruses (HCoV) OC43, 229E, NL63, and HKU1 are common respiratory viruses which cause various respiratory diseases, including pneumonia. There is a paucity of evidence on the epidemiology and clinical manifestations of these four HCoV strains worldwide. We collected 11,399 throat swabs from hospitalized children with acute respiratory tract infection from July 2009 to June 2016 in Guangzhou, China. These were tested for four strains of HCoV infection using real-time polymerase chain reaction (PCR). HCoV-positive patients were then tested for 11 other respiratory pathogens. 4.3% (489/11399) of patients were positive for HCoV, of which 3.0% were positive for OC43 (346/11399), 0.6% for 229E (65/11399), 0.5% for NL63 (60/11399), and 0.3% for HKU1 (38/11399). Patients aged 7–12 months had the highest prevalence of HCoV and OC43 when compared with other age groups (p < 0.001). The peak seasons of infection varied depending on the HCoV strain. Patients infected with a single strain of HCoV infection were less likely to present fever (≥ 38 °C) (p = 0.014) and more likely to present pulmonary rales (p = 0.043) than those co-infected with more than one HCoV strain or other respiratory pathogens. There were also significant differences in the prevalence of certain symptoms, including coughing (p = 0.032), pneumonia (p = 0.026), and abnormal pulmonary rales (p = 0.002) according to the strain of HCoV detected. This retrospective study of the prevalence of four HCoV strains and clinical signs among a large population of pediatric patients in a subtropical region of China provides further insight into the epidemiology and clinical features of HCoV.

negative: Novel Coronavirus COVID-19 Strike on Arab Countries and Territories: A Situation Report I The novel Coronavirus (COVID-19) is an infectious disease caused by a new virus called COVID-19 or 2019-nCoV that first identified in Wuhan, China. The disease causes respiratory illness (such as the flu) with other symptoms such as a cough, fever, and in more severe cases, difficulty breathing. This new Coronavirus seems to be very infectious and has spread quickly and globally. In this work, information about COVID-19 is provided and the situation in Arab countries and territories regarding the COVID-19 strike is presented. The next few weeks main expectations is also given.

negative: Facing the threat of influenza pandemic - roles of and implications to general practitioners The 2009 pandemic of H1N1 influenza, compounded with seasonal influenza, posed a global challenge. Despite the announcement of post-pandemic period on 10 August 2010 by theWHO, H1N1 (2009) virus would continue to circulate as a seasonal virus for some years and national health authorities should remain vigilant due to unpredictable behaviour of the virus. Majority of the world population is living in countries with inadequate resources to purchase vaccines and stockpile antiviral drugs. Basic hygienic measures such as wearing face masks and the hygienic practice of hand washing could reduce the spread of the respiratory viruses. However, the imminent issue is translating these measures into day-to-day practice. The experience from Severe Acute Respiratory Syndrome (SARS) in Hong Kong has shown that general practitioners (GPs) were willing to discharge their duties despite risks of getting infected themselves. SARS event has highlighted the inadequate interface between primary and secondary care and valuable health care resources were thus inappropriately matched to community needs. There are various ways for GPs to contribute in combating the influenza pandemic. They are prompt in detecting and monitoring epidemics and mini-epidemics of viral illnesses in the community. They can empower and raise the health literacy of the community such as advocating personal hygiene and other precautious measures. GPs could also assist in the development of protocols for primary care management of patients with flu-like illnesses and conduct clinical audits on the standards of preventive and treatment measures. GPs with adequate liaison with public health agencies would facilitate early diagnosis of patients with influenza. In this article, we summarise the primary care actions for phases 4-6 of the pandemic. We shall discuss the novel roles of GPs as alternative source of health care for patients who would otherwise be cared for in the secondary care level. The health care system would thus remain sustainable during the public health crisis.

negative: SARS-associated Coronavirus Transmission, United States To better assess the risk for transmission of the severe acute respiratory syndrome–associated coronavirus (SARS-CoV), we obtained serial specimens and clinical and exposure data from seven confirmed U.S. SARS patients and their 10 household contacts. SARS-CoV was detected in a day-14 sputum specimen from one case-patient and in five stool specimens from two case-patients. In one case-patient, SARS-CoV persisted in stool for at least 26 days after symptom onset. The highest amounts of virus were in the day-14 sputum sample and a day-14 stool sample. Residual respiratory symptoms were still present in recovered SARS case-patients 2 months after illness onset. Possible transmission of SARS-CoV occurred in one household contact, but this person had also traveled to a SARS-affected area. The data suggest that SARS-CoV is not always transmitted efficiently. Laboratory diagnosis of SARS-CoV infection is difficult; thus, sputum and stool specimens should be included in the diagnostic work-up for SARS-CoV infection.

negative: RT-PCR and Electrospray Ionization Mass Spectrometry (RT-PCR/ESI-MS) for Identifying Acute Viral Upper Respiratory Tract Infections Diagnosis of respiratory viruses traditionally relies on culture or antigen detection.We aimed to demonstrate capacity of the RT-PCR/ESI-MS platform to identify clinical relevant respiratory viruses in nasopharyngeal aspirate (NPA) samples and compare the diagnostic performance characteristics relative to conventional culture- and antigen-based methods. A RT-PCR/ESI-MS respiratory virus surveillance kit designed to detect respiratory syncytial virus, influenza A and B, parainfluenza types 1-4, adenoviridae types A-F, coronaviridae, human bocavirus, and human metapneumovirus was evaluated using both mock-ups and frozen archived NPA (N=280), 95 of which were positive by clinical virology methods. RT-PCR/ESI-MS detected 74/95 (77.9%) known positive samples and identified an additional 13/185 (7%) from culture negative samples. Viruses that are non-detectable with conventional methods were also identified. Viral load was semi-quantifiable and ranged from 2,400 to >320,000copies/ml. Time to results was 8hrs. RT-PCR/ESI-MS showed promise in rapid detection of respiratory viruses, merits further evaluation for use in clinical settings.

negative: Epidemiological and clinical characteristics of 46 newly-admitted coronavirus disease 2019 cases in Beijing/ 中华传染病杂志 Objective@#To investigate and analyze the epidemiological and clinical characteristics of some cases of coronavirus disease 2019 (COVID-19) in Beijing.@*Methods@#A retrospective study was conducted to analyze the data of 46 patients with COVID-19 in Beijing from 20th January 2020 to 8th February 2020 at the Fifth Medical Center of the PLA General Hospital. Features of clinical symptoms, laboratory inspections and imaging inspections were analyzed. Statistical analysis used Fisher exact test. If P<0.05, post-hoc test was used for pairwise comparison, and the statistics were corrected by Bonferroni test.@*Results@#Among the 46 patients included in this study, 27 were male and 19 were female. The age range was between 3 - 79 years old, and the mean age was (41.8 ± 16.3) years old. The average incubation period was (4.85 ± 3.00) days. A total of 26 cases (56.5%) were clustered patients, and 12 (26.1%), 23 (50.0%) and 11 patients (23.9%)were assigned to the mild group, common group, and sever group, respectively. Fever (39.8%), cough (27.6%), and fatigue (25.3%) was the main clinical symptom for these patients. The decrease in white blood cell counts occurred in 12 patients, four had the decrease in T lymphocyte counts, 17 had the decrease in CD4 + T lymphocyte counts, seven had the decrease in CD8 + T lymphocyte counts, 21 had the increase level of C-reactive protein (45.7%), and IL-6 level increased in 32 cases (69.6%), erythrocyte sedimentation rate increased in 20 cases(50.0%), serum ferritin level increased in 26 cases (56.5%), and blood lactate level increased in nine cases. There was a statistically significant difference in the number of cases in which the absolute value of T lymphocytes and of CD8 + T lymphocytes decreased among the mild, common and severe groups (all P<0.05). Comparing the number of cases in the three groups with elevated C-reactive protein, interleukin-6, erythrocyte sedimentation rate, serum ferritin and blood lactate levels, the differences were statistically significant (all P<0.05). The number of cases with elevated C-reactive protein levels was higher in severe group than that in mild and common group. The number of cases with elevated interleukin-6, erythrocyte sedimentation rate, and serum ferritin levels were higher in severe group than in mild group. The number of cases with elevated blood lactic acid levels was higher in severe group than in mild group. The differences between the above groups were statistically significant (both adjusted P<0.017). Analysis of chest X-rays showed that 34 patients (73.9%) had inflammation in the lungs.@*Conclusions@#The epidemiological characteristics of cases with COVID-19 in Beijing are mainly imported cases and clustered cases. The clinical manifestations are mainly fever , fatigue and cough. C-reactive protein, interleukin-6, red blood cell sedimentation rate, serum ferritin and blood lactate levels are higher in severe patients.

negative: Lack of detection of Middle East respiratory syndrome coronavirus in mild and severe respiratory infections in Catalonia, northeastern Spain Surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted to explore the possible introduction and circulation of this novel virus in Catalonia, northeastern Spain. Five hundred and sixty-three samples from mild and severe respiratory infections collected between January 2012 and April 2013 were screened using real-time RT-PCR. All samples were negative, suggesting that MERS-CoV is not circulating silently in Catalonia.

negative: COVID-19 in a patient with long-term use of glucocorticoids: A study of a familial cluster Abstract Clusters of patients with novel coronavirus disease 2019 (COVID-19) have been successively reported globally. Studies show clear person-to-person transmission. The average incubation period is 2–14 days, and mostly 3–7 days. However, in some patients, this period may be longer. Here, we report a familial cluster of COVID-19 where a 47-year-old woman with long-term use of glucocorticoids did not develop any symptoms within the 14-day quarantine period but was confirmed with COVID-19 by tested positive of antibody on day 40 after she left Wuhan. Almost at the same time, her father and sister were diagnosed with COVID-19. The results suggest that the long-term use of glucocorticoids might cause atypical infections, a long incubation period, and extra transmission of COVID-19.

negative: A new threat from an old enemy: Re-emergence of coronavirus (Review) The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus-associated disease, the spread and lethality of the 2019 outbreak (COVID-19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.

negative: Development and evaluation of multiplex real-time RT-PCR assays for seasonal, pandemic A/H1pdm09 and avian A/H5 influenza viruses detection Since the pandemic influenza A (H1N1) 2009 ((H1N1)pdm09) virus spread all over the world, the (H1N1)pdm09 virus has been circulating with seasonal influenza viruses. We developed rapid and sensitive one-step multiplex real-time RT-PCR assays (rRT-PCR) for simultaneous detection of influenza viruses currently circulating in humans, and the avian A/H5 virus. The detection limit of each assay was 4.8 to 1 copies per reaction and no cross-reactivity with other major respiratory pathogens was found. Analytical positive predictive value (PPV), negative predictive value (NPV) sensitivity and specificity were 100%, 94.1%, 93.7% and 100%, respectively. Clinical evaluation revealed that 1,976 (16.5%) of 11,963 throat swabs from patients with respiratory symptoms were confirmed as 1,651 (83.6%) A/H1pdm09, 308 (15.6%) A/H3 and 17 (0.8%) B virus during the 2010–2011 influenza season. Collectively, the multiplex rRT-PCR assays described here provide a practical tool for reliable implementation of influenza surveillance and diagnosis.

negative: An SEIR Model for Assessment of Current COVID-19 Pandemic Situation in the UK The ongoing COVID-19 pandemic spread to the UK in early 2020 with the first few cases being identified in late January. A rapid increase in confirmed cases started in March, and the number of infected people is however unknown, largely due to the rather limited testing scale. A number of reports published so far reveal that the COVID-19 has long incubation period, high fatality ratio and non-specific symptoms, making this novel coronavirus far different from common seasonal influenza. In this note, we present a modified SEIR model which takes into account the time lag effect and probability distribution of model states. Based on the proposed model, it is estimated that the actual total number of infected people by 1 April in the UK might have already exceeded 610,000. Average fatality rates under different assumptions at the beginning of April 2020 are also estimated. Our model also reveals that the R0 value is between 7.5-9 which is much larger than most of the previously reported values. The proposed model has a potential to be used for assessing future epidemic situations under different intervention strategies.

negative: Health shocks and their long-lasting impact on health behaviors: Evidence from the 2009 H1N1 pandemic in Mexico Abstract Worldwide, the leading causes of death could be avoided with health behaviors that are low-cost but also difficult to adopt. We show that exogenous health shocks could facilitate the adoption of these behaviors and provide long-lasting effects on health outcomes. Specifically, we exploit the spatial and temporal variation of the 2009 H1N1 influenza pandemic in Mexico and show that areas with a higher incidence of H1N1 experienced larger reductions in diarrhea-related cases among young children. These reductions continue even three years after the shock ended. Health improvements and evidence of information seeking via Google searches were consistent with changes in hand washing behaviors. Several robustness checks validate our findings and mechanism.

negative: The baculovirus expression vector system: A commercial manufacturing platform for viral vaccines and gene therapy vectors The baculovirus expression vector system (BEVS) platform has become an established manufacturing platform for the production of viral vaccines and gene therapy vectors. Nine BEVS‐derived products have been approved – four for human use (Cervarix®, Provenge®, Glybera® and Flublok®) and five for veterinary use (Porcilis® Pesti, BAYOVAC CSF E2®, Circumvent® PCV, Ingelvac CircoFLEX® and Porcilis® PCV). The BEVS platform offers many advantages, including manufacturing speed, flexible product design, inherent safety and scalability. This combination of features and product approvals has previously attracted interest from academic researchers, and more recently from industry leaders, to utilize BEVS to develop next generation vaccines, vectors for gene therapy, and other biopharmaceutical complex proteins. In this review, we explore the BEVS platform, detailing how it works, platform features and limitations and important considerations for manufacturing and regulatory approval. To underscore the growth in opportunities for BEVS‐derived products, we discuss the latest product developments in the gene therapy and influenza vaccine fields that follow in the wake of the recent product approvals of Glybera® and Flublok®, respectively. We anticipate that the utility of the platform will expand even further as new BEVS‐derived products attain licensure. Finally, we touch on some of the areas where new BEVS‐derived products are likely to emerge.

negative: The Role of EGFR in Influenza Pathogenicity: Multiple Network-Based Approaches to Identify a Key Regulator of Non-lethal Infections Despite high sequence similarity between pandemic and seasonal influenza viruses, there is extreme variation in host pathogenicity from one viral strain to the next. Identifying the underlying mechanisms of variability in pathogenicity is a critical task for understanding influenza virus infection and effective management of highly pathogenic influenza virus disease. We applied a network-based modeling approach to identify critical functions related to influenza virus pathogenicity using large transcriptomic and proteomic datasets from mice infected with six influenza virus strains or mutants. Our analysis revealed two pathogenicity-related gene expression clusters; these results were corroborated by matching proteomics data. We also identified parallel downstream processes that were altered during influenza pathogenesis. We found that network bottlenecks (nodes that bridge different network regions) were highly enriched in pathogenicity-related genes, while network hubs (highly connected network nodes) were significantly depleted in these genes. We confirmed that this trend persisted in a distinct virus: Severe Acute Respiratory Syndrome Coronavirus (SARS). The role of epidermal growth factor receptor (EGFR) in influenza pathogenesis, one of the bottleneck regulators with corroborating signals across transcript and protein expression data, was tested and validated in additional mouse infection experiments. We demonstrate that EGFR is important during influenza infection, but the role it plays changes for lethal versus non-lethal infections. Our results show that by using association networks, bottleneck genes that lack hub characteristics can be used to predict a gene’s involvement in influenza virus pathogenicity. We also demonstrate the utility of employing multiple network approaches for analyzing host response data from viral infections.

negative: 2019 Novel Coronavirus Outbreak: SOS Alert for Dentists On January 31, 2020, novel coronavirus (nCoV), a zoonotic virus yet to be identified into the taxonomy, created a powerful ripple through mankind that the World Health Organization has declared a global health emergency.1 This is definitely not the first time that an alarm has been rung by this family of viruses. Epidemic impact of severe acute respiratory syndrome (SARS) due to SARS CoV and Middle East respiratory syndrome (MERS) by MERS CoV has engraved their place in the scientific literature.2 In general, CoV is known to cause respiratory diseases in humans and accounts for one-third of common cold infections.3 The current outbreak by 2019 nCoV in the Chinese city of Wuhan began in December 2019, has infected nearly 102,188 with 3,491 deaths reported as of March 7, 2020, and has spread to nearly 92 countries.1,4 An assumed incubation period between 2 and 14 days, with flu-like symptoms, may progress into severe pneumonia or acute respiratory distress syndrome which may be the reason for mortality.5,6.

negative: First COVID-19 mortality case in Taiwan with bacterial co-infection by national surveillance of critically ill patients with influenza-negative pneumonia Abstract A 63-year-old diabetic smoker with alcoholism was the first mortality case of coronavirus disease 2019 (COVID-19) in Taiwan. As concurrently infected with Klebsiella pneumoniae and subsequently with Klebsiella aerogenes, he was exposed by a national survey of patients with critically influenza-negative pneumonia. We recommend COVID-19 screening for patients with severe flu-like syndrome and protecting health-care workers from being infected.

negative: Pandemics: is hoping for the best enough? Albert Osterhaus reflects on the reasons for the increase in emerging pandemics and how we are coping with these situations. Although we might risk over-reacting, better safe than sorry is still the most reasonable policy.

negative: Forecasting the 2013–2014 Influenza Season Using Wikipedia Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are applied to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.

negative: Evolution of genomes, host shifts and the geographic spread of SARS‐CoV and related coronaviruses Severe acute respiratory syndrome (SARS) is a novel human illness caused by a previously unrecognized coronavirus (CoV) termed SARS‐CoV. There are conflicting reports on the animal reservoir of SARS‐CoV. Many of the groups that argue carnivores are the original reservoir of SARS‐CoV use a phylogeny to support their argument. However, the phylogenies in these studies often lack outgroup and rooting criteria necessary to determine the origins of SARS‐CoV. Recently, SARS‐CoV has been isolated from various species of Chiroptera from China (e.g., Rhinolophus sinicus) thus leading to reconsideration of the original reservoir of SARS‐CoV. We evaluated the hypothesis that SARS‐CoV isolated from Chiroptera are the original zoonotic source for SARS‐CoV by sampling SARS‐CoV and non‐SARS‐CoV from diverse hosts including Chiroptera, as well as carnivores, artiodactyls, rodents, birds and humans. Regardless of alignment parameters, optimality criteria, or isolate sampling, the resulting phylogenies clearly show that the SARS‐CoV was transmitted to small carnivores well after the epidemic of SARS in humans that began in late 2002. The SARS‐CoV isolates from small carnivores in Shenzhen markets form a terminal clade that emerged recently from within the radiation of human SARS‐CoV. There is evidence of subsequent exchange of SARS‐CoV between humans and carnivores. In addition SARS‐CoV was transmitted independently from humans to farmed pigs (Sus scrofa). The position of SARS‐CoV isolates from Chiroptera are basal to the SARS‐CoV clade isolated from humans and carnivores. Although sequence data indicate that Chiroptera are a good candidate for the original reservoir of SARS‐CoV, the structural biology of the spike protein of SARS‐CoV isolated from Chiroptera suggests that these viruses are not able to interact with the human variant of the receptor of SARS‐CoV, angiotensin‐converting enzyme 2 (ACE2). In SARS‐CoV we study, both visually and statistically, labile genomic fragments and, putative key mutations of the spike protein that may be associated with host shifts. We display host shifts and candidate mutations on trees projected in virtual globes depicting the spread of SARS‐CoV. These results suggest that more sampling of coronaviruses from diverse hosts, especially Chiroptera, carnivores and primates, will be required to understand the genomic and biochemical evolution of coronaviruses, including SARS‐CoV. © The Willi Hennig Society 2008.

negative: Disparities in Age-Specific Morbidity and Mortality from SARS-CoV-2 in China and the Republic of Korea We analyzed age- and sex-specific morbidity and mortality data from SARS-COV-2 pandemic in China and Republic of Korea (ROK). Data from China exhibit a standard Gaussian distribution with peak morbidity in the 50-59 years cohort, while the ROK data have a bimodal distribution with highest morbidity in the 20-29 years cohort.

negative: Awaiting the Second Big Data Revolution: From Digital Noise to Value Creation “Big data”—the collection of vast quantities of data about individual behavior via online, mobile, and other data-driven services—has been heralded as the agent of a third industrial revolution—one with raw materials measured in bits, rather than tons of steel or barrels of oil. Yet the industrial revolution transformed not just how firms made things, but the fundamental approach to value creation in industrial economies. To date, big data has not achieved this distinction. Instead, today’s successful big data business models largely use data to scale old modes of value creation, rather than invent new ones altogether. Moreover, today’s big data cannot deliver the promised revolution. In this way, today’s big data landscape resembles the early phases of the first industrial revolution, rather than the culmination of the second a century later. Realizing the second big data revolution will require fundamentally different kinds of data, different innovations, and different business models than those seen to date. That fact has profound consequences for the kinds of investments and innovations firms must seek, and the economic, political, and social consequences that those innovations portend.

negative: Can the summer temperatures reduce COVID-19 cases? OBJECTIVE: Despite huge global, national, and local preventive measures including travel restriction, social distancing, and quarantines, the outbreak of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develops the coronavirus disease 2019 (COVID-19) worldwide pandemic. SARS-CoV-2 emerging from Wuhan, China, took only three months to cover >200 countries worldwide by infecting more than 2.4 million people and killing more than 150,000 people. Although this infection at the early stage creates seasonal flu-like symptoms with a higher illness, it eventually causes a higher mortality. Epidemiological studies not only find the causes of many health issues but also suggest preventive measures. This study aimed to see the link between environment temperature and COVID-19 cases. STUDY DESIGN: The monthly average environment temperature (MAET) and various COVID-19 cases of a country were collected and analyzed to see the relationship between these parameters. METHODS: Univariate analysis and statistical modeling were used to determine the relationship between environment temperature and different COVID-19 cases. RESULTS: This study found that the majorities of the countries having higher COVID-19 cases are located in the higher latitude (colder region) in the globe. As of 20th April data available, statistical analyses by various methods have found that strong negative correlations with statistical significance exist between MAET and several COVID-19 cases including total cases, active cases, and cases per million of a country (Spearman correlation coefficients were -0.45, -0.42, and -0.50 for total cases, active cases, and cases/per million, respectively). Analysis by the statistical log-linear regression model further supports that the chance of patients to contract COVID-19 is less in warmer countries than in colder countries. CONCLUSION: This pilot study proposes that cold environment may be an additional risk factor for COVID-19 cases.

negative: Mathematical Modeling of Epidemic Diseases; A Case Study of the COVID-19 Coronavirus The outbreak of the Coronavirus COVID-19 has taken the lives of several thousands worldwide and locked-out many countries and regions, with yet unpredictable global consequences. In this research we study the epidemic patterns of this virus, from a mathematical modeling perspective. The study is based on an extensions of the well-known susceptible-infected-recovered (SIR) family of compartmental models. It is shown how social measures such as distancing, regional lockdowns, quarantine and global public health vigilance, influence the model parameters, which can eventually change the mortality rates and active contaminated cases over time, in the real world. As with all mathematical models, the predictive ability of the model is limited by the accuracy of the available data and to the so-called level of abstraction used for modeling the problem. In order to provide the broader audience of researchers a better understanding of spreading patterns of epidemic diseases, a short introduction on biological systems modeling is also presented and the Matlab source codes for the simulations are provided online.

negative: Influence of the Pressure Difference and Door Swing on Heavy Contaminants Migration between Rooms This paper presents the results of investigations whose aim was to describe the influence of the pressure difference level on the ability of contaminants migration between neighbouring rooms in dynamic conditions associated with door swing. The analysis was based on airflow visualization made with cold smoke, which simulated the heavy contaminants. The test room was pressurized to a specific level and then the door was opened to observe the trail of the smoke plume in the plane of the door. The door was opened in both directions: to the positively and negatively pressurized room. This study focuses on the visualization of smoke plume discharge and an uncertainty analysis is not applicable. Unlike other studies which focus on the analysis of pressure difference, the present study looks at the contaminants which are heavier than air and on “pumping out” the contaminants by means of door swing. Setting the proper level of pressure difference between the contaminated room and the neighbouring rooms can prove instrumental in ensuring protection against toxic contaminants migration. This study helped to establish the threshold of pressure difference necessary to reduce migration of heavy contaminants to neighbouring rooms.

negative: Web-based participatory surveillance of infectious diseases: the Influenzanet participatory surveillance experience To overcome the limitations of the state-of-the-art influenza surveillance systems in Europe, we established in 2008 a European-wide consortium aimed at introducing an innovative information and communication technology approach for a web-based surveillance system across different European countries, called Influenzanet. The system, based on earlier efforts in The Netherlands and Portugal, works with the participation of the population in each country to collect real-time information on the distribution of influenza-like illness cases through web surveys administered to volunteers reporting their symptoms (or lack of symptoms) every week during the influenza season. Such a large European-wide web-based monitoring infrastructure is intended to rapidly identify public health emergencies, contribute to understanding global trends, inform data-driven forecast models to assess the impact on the population, optimize the allocation of resources, and help in devising mitigation and containment measures. In this article, we describe the scientific and technological issues faced during the development and deployment of a flexible and readily deployable web tool capable of coping with the requirements of different countries for data collection, during either a public health emergency or an ordinary influenza season. Even though the system is based on previous successful experience, the implementation in each new country represented a separate scientific challenge. Only after more than 5 years of development are the existing platforms based on a plug-and-play tool that can be promptly deployed in any country wishing to be part of the Influenzanet network, now composed of The Netherlands, Belgium, Portugal, Italy, the UK, France, Sweden, Spain, Ireland, and Denmark.

negative: COVID-19 Blockchain Framework: Innovative Approach The world is currently witnessing dangerous shifts in the epidemic of emerging SARS-CoV-2, the causative agent of (COVID-19) coronavirus. The infection, and death numbers reported by World Health Organization (WHO) about this epidemic forecasts an increasing threats to the lives of people and the economics of countries. The greatest challenge that most governments are currently suffering from is the lack of a precise mechanism to detect unknown infected cases and predict the infection risk of COVID-19 virus. In response to mitigate this challenge, this study proposes a novel innovative approach for mitigating big challenges of (COVID-19) coronavirus propagation and contagion. This study propose a blockchain-based framework which investigate the possibility of utilizing peer-to peer, time stamping, and decentralized storage advantages of blockchain to build a new system for verifying and detecting the unknown infected cases of COVID-19 virus. Moreover, the proposed framework will enable the citizens to predict the infection risk of COVID-19 virus within conglomerates of people or within public places through a novel design of P2P-Mobile Application. The proposed approach is forecasted to produce an effective system able to support governments, health authorities, and citizens to take critical decision regarding the infection detection, infection prediction, and infection avoidance. The framework is currently being developed and implemented as a new system consists of four components, Infection Verifier Subsystem, Blockchain platform, P2P-Mobile Application, and Mass-Surveillance System. This four components work together for detecting the unknown infected cases and predicting and estimating the infection Risk of Corona Virus (COVID-19).

negative: Issues Relevant to the Adoption and Modification of Hospital Infection-Control Recommendations for Avian Influenza (H5N1 Infection) in Developing Countries The reemergence of avian influenza (H5N1 infection) has heightened concern for a potential human influenza pandemic. Recommendations regarding preparation for a global avian influenza pandemic are available, and it is imperative that health care workers participate in preparedness planning and training. In developing countries, health care worker preparedness training should address the modes of avian influenza transmission and specify how to implement appropriate infection-control strategies to prevent and control the spread of avian influenza. We provide evidence for avian influenza transmission methods and identify prevention strategies relevant to infection control for hospitals in developing countries. Pandemic influenza preparedness plans must include health care administrative support, mechanisms to rapidly create temporary isolation facilities, systems to restrict access to exposed health care workers, and plans to involve specialists to screen and identify cases early, to provide for continuous monitoring to ensure adherence to optimal infection-control practices, and to provide regular feedback to health care workers

negative: Biomimetic nanoparticles as universal influenza vaccine Abstract Pandemic virus infections, such as seasonal influenza, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, pose a major public health threat globally. 1 , 2 Much effort has been devoted to suppress the virus, including vaccine prevention, autoimmunity enhancement, and anti-virus drugs treatment. Among these strategies, development of novel and improved vaccine technologies attracts broad attention as they can nip the virus outbreak in the bud and avoid the appearance of public health emergency. Therefore, Wang et al. 1 recently offer a promising means: they develop universal viral vaccine through biomimetic nanoparticles.

negative: The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

negative: Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza in 2015–2016: a hospital-based test-negative case–control study in Lithuania OBJECTIVE: A case–control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015–2016 influenza season. METHODS: A study was performed in three departments in Lithuania between 1 December 2015 and 1 May 2016. Data on demographic and clinical characteristics including influenza vaccination status were collected from the patients recommended to receive the seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Ninety-one (56.4%) of the 163 included subjects were ≥65 years old. Fifteen (9.2%) subjects were vaccinated against influenza at least 2 weeks before the onset of influenza symptoms, 12 of them were ≥65 years old. Of the 72 (44.2%) influenza virus positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was a co-infection. Unadjusted SIVE against any influenza, influenza type A and influenza A(H1N1)pdm09 was 57% (95% CI −41% to 87%), 52% (95% CI −57% to 85%) and 70% (95% CI −43% to 94%) respectively. CONCLUSION: Although SIVE estimates were not statistically significant the point estimates suggest moderate effectiveness against influenza type A.

negative: General Guidelines in the Management of an Obstetrical Patient on the Labor and Delivery Unit during the COVID-19 Pandemic Novel coronavirus disease 2019 (COVID-19) is a respiratory tract infection that was first identified in China. Since its emergence in December 2019, the virus has rapidly spread, transcending geographic barriers. The World Health Organization and the Centers for Disease Control and Prevention have declared COVID-19 as a public health crisis. Data regarding COVID-19 in pregnancy is limited, consisting of case reports and small cohort studies. However, obstetric patients are not immune from the current COVID-19 pandemic, and obstetric care will inevitably be impacted by the current epidemic. As such, clinical protocols and practice on labor and delivery units must adapt to optimize the safety of patients and health care workers and to better conserve health care resources. In this commentary, we provide suggestions to meet these goals without impacting maternal or neonatal outcomes. Key Points • Novel coronavirus disease 2019 (COVID-19) is a pandemic. • COVID-19 impacts care of obstetric patients. • Health care should be adapted for the COVID-19 pandemic.

negative: Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Public Health Emergency of International Concern. However, so far, there are still controversies about the source of the virus and its intermediate host. Here, we found the novel coronavirus was closely related to coronaviruses derived from five wild animals, including Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus, and was in the same branch of the phylogenetic tree. However, genome and ORF1a homology show that the virus is not the same coronavirus as the coronavirus derived from these five animals, whereas the virus has the highest homology with Bat coronavirus isolate RaTG13.

negative: Rare tendency of catching cold in Parkinson’s disease Abstract We carried out a study, using a questionnaire, that indicated that persons with Parkinson’s disease (PD) catch relatively fewer colds that are unusually mild. This tendency seems to have no clear relationship to the severity of the PD, the time after the onset of PD, or whether or not the patient is taking antiparkinsonian drugs either as mono therapy or in combination. The study found no similar phenomena among spouses of the PD patients or among patients with cerebrovascular disease. These results suggest that a low frequency of colds is a unique feature in persons with PD.

negative: COVID-19: How to make between-country comparisons BACKGROUND: Different countries have adopted different containment and testing strategies for SARS-CoV-2. The difference in testing makes it difficult to compare the effect of different containment strategies. This study proposes methods to allow a direct comparison and presents the results. DESIGN: Publicly available data on the numbers of reported COVID-19-related deaths between 01 January and 17 April 2020 were compared between countries. RESULTS: The numbers of cases or deaths per 100,000 inhabitants gave severely biased comparisons between countries. Only the number of deaths expressed as a percentage of the number of deaths on day 25 after the first reported COVID-19-related death allowed a direct comparison between countries. From this comparison clear differences were observed between countries, associated with the timing of the implementation of containment measures. CONCLUSIONS: Comparisons between countries are only possible when simultaneously taking into account that the virus does not arrive in all countries simultaneously, absolute numbers are incomparable due to different population sizes, rates per 100,000 of the population are incomparable because not all countries are affected homogeneously, susceptibility to death by COVID-19 can differ between populations, and a death is only reported as a COVID-19-related death if the patient was diagnosed with SARS-CoV-2 infection. With the current methods, all these factors were accounted for and an unbiased direct comparison between countries was established. This comparison confirmed that early adoption of containment strategies is key in flattening the curve of the epidemic.

negative: Experience of a screening centre for influenza A/H1N1: the first 50 days. BACKGROUND The authors' emergency department (ED) served as Singapore's screening centre for influenza H1N1 cases. The aims of the study were to describe their screening experience and to compare clinical and laboratory features of H1N1 versus seasonal flu cases. METHODOLOGY The authors conducted a prospective observational study on consecutive patients aged 16 years and above presenting to a busy, urban ED for H1N1 screening over 50 days. Clinical, laboratory, radiological and PCR data were collected from the hospital electronic databases. Primary outcomes were proportions of confirmed H1N1 cases and their distribution of clinical, laboratory and radiological features. Secondary outcomes were comparison of clinical and laboratory features of H1N1 versus seasonal flu cases. Data were analysed using descriptive statistics and univariate analysis was used to compare factors between the two groups. A p value <0.05 was considered statistically significant. RESULTS 1205 patients were screened. 31 (2.6%) and 133 (11%) of them had H1N1 and seasonal flu infections, respectively. The two groups had similar symptoms. There were six clinical and two laboratory features with statistically significant differences between H1N1 and seasonal flu cases. Clinical factors were travel or contact history, median age, respiratory rate, diastolic blood pressure and length of hospital stay. Laboratory factors were median platelet and lymphocyte counts. CONCLUSIONS The authors report their experience as the nation's H1N1 screening centre. They identified factors that were different between H1N1 and seasonal flu cases. Future research is needed to elucidate if and how this information can be used as a screening tool for H1N1.

negative: Enhancing the Teaching of Evolution in Public Health SUMMARY: Public health courses are emerging as popular undergraduate offerings, especially at universities with schools of public health. It is important to note that evolution has shaped the burden of disease in the modern world in which we practice and educate for public health. Human cultures and technologies have modified life on Planet Earth and have co-evolved with myriad other species, including microorganisms, plant and animal sources of food, invertebrate vectors of disease, and intermediate bird, mammal, and primate hosts. Molecular mechanisms of evolution have produced differential resistance or susceptibility to infectious agents, including malaria, plague, smallpox, TB, measles, and diarrheal and respiratory diseases. The domestication of sheep and cattle led to natural selection in favor of human populations able to digest milk throughout life through persistence into adulthood of lactase enzyme expression in the intestine, a major story of anthropology. The emergence of a “Western diet” of dairy, refined cereal grains, refined sugars, vegetable oils, alcoholic beverages, salt, and omega-6-rich meats has dramatically altered glycemic load, fatty acid composition, macro-nutrients, acid-base balance, sodium/potassium ratio, and fiber content. This is a major story of nutrition and disease. The results include epidemics of atherosclerotic cardiovascular disease, obesity, diabetes, high blood pressure, osteoporosis, certain cancers, and bowel, inflammatory, and autoimmune disorders. Another interesting phenomenon is the selection of excessive hemostatic activity from platelets and the plasma clotting proteins; what was protective against death from bleeding after injuries among hunter-gatherers or from pregnancy-related hemorrhage now contributes to thrombosis underlying heart attacks and strokes. Conversely, there is little pressure against hemostasis and thrombosis since deaths from these causes occur mostly after the reproductive years of life. Learning about evolution over millennia for humans and over hours or days for microbes enlivens the experience of understanding evolutionary biology in public health context.

negative: Coronavirus (COVID-19): A Review of Clinical Features, Diagnosis, and Treatment Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. A total of six species have been identified to cause disease in humans. They are known to infect the neurological, respiratory, enteric, and hepatic systems. The past few decades have seen endemic outbreaks in the form of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome related coronavirus (SARS-CoV). Yet again, we see the emergence of another outbreak due to a new strain called the SARS-CoV-2 virus. The most recent outbreak initially presented as pneumonia of unknown etiology in a cluster of patients in Wuhan, China. The epicenter of infection was linked to seafood and exotic animal wholesale markets in the city. SARS-CoV-2 is highly contagious and has resulted in a rapid pandemic of COVID-19. As the number of cases continues to rise, it is clear that these viruses pose a threat to public health. This review will introduce a general overview of coronavirus and describe the clinical features, evaluation, and treatment of COVID-19 patients. It will also provide a means to raise awareness among primary and secondary healthcare providers during the current pandemic. Furthermore, our review focuses on the most up-to-date clinical information for the effective management, prevention, and counseling of patients worldwide.

negative: Coronavirus Disease 2019 in an Orthotopic Liver Transplant Recipient Living with Human Immunodeficiency Virus Coronavirus disease 2019 (COVID-19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with flu-like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID-19-infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID-19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well-controlled HIV who successfully recovered from a mild, flu-like illness attributed to SARS-CoV-2.

negative: Side by side comparison of three fully automated SARS-CoV-2 antibody assays with a focus on specificity Background: In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies have become available quickly. However, the clinical performance of many of them is still insufficiently described. Therefore we compared three commercial, CE-marked, SARS-CoV-2 antibody assays side by side. Methods: We included a total of 1,154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients ([≥]14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. Results: All three assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers' specifications, sensitivities only ranged from 83.1% to 89.2%. Although the three methods were in good agreement (Cohen's Kappa 0.71-0.87), McNemar's test revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictability at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Roche, Abbott, and DiaSorin, respectively. Conclusion: We find diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictability of these tests.

negative: Impacts of rapid flu clinic services at an emergency department during the pandemic flu season BACKGROUND: We performed an assessment of an independent rapid flu clinic service (RFCS) unit, which was set up outside the emergency department (ED) during the 2009 H1N1 pandemic season. The unit was able to relieve the crowding of regular ambulatory and emergency services. METHODS: Between August and December 2009, a total of 6,152 patients with influenza-like illness were enrolled in this observational retrospective study. Patients with positive influenza tests were interviewed to evaluate the efficiency of RFCS. RESULTS: The mean length of stay (LOS) for the RFCS was 50 minutes, which was shorter than the LOS for ambulatory services (1 hour) and regular ED services (3.5 hours). Overall, 88% of patients were satisfied with the RFCS. Of 6,152 patients receiving flu tests, 1,235 (20%) had a positive result. Fever (odds ratio [OR], 4.28, 95% confidence interval [CI]: 3.11-5.89), fever combined with cough and sore throat (OR, 2.52; 95% CI: 2.18-2.92), fever combined with sore throat (OR, 2.42; 95% CI: 2.13-2.75), history of contacting confirmed flu patients within 7 days (OR, 2.40; 95% CI: 2.07-2.78), fever combined with cough (OR, 2.19; 95% CI: 1.92-2.47), sore throat (OR, 2.03, 95% CI: 1.79-2.30); and cough (OR, 1.91, 95% CI: 1.69-2.17) were significantly associated with positive influenza tests. CONCLUSION: Setting up the RFSC was beneficial to health care facilities during a pandemic flu season.

negative: Online Information Search During COVID-19 Public information search data from sources such as Google Trends affords researchers a perspective on what society does not know, or what society wants to find out prompted by, or in response to, developments in societal communication and news media events. In times of crisis, online public information search thus offers a window into the most urgent concerns of, and demands by society. By extension, such data offers a window into upcoming, and currently pressing demands on businesses, policymakers and researchers. This research note aims to illustrate some of these themes with a visual-based overview of the current COVID-19 / Coronavirus crisis.

negative: Evaluation of the Xpert Flu A Panel nucleic acid amplification-based point-of-care test for influenza A virus detection and pandemic H1 subtyping Abstract Background Influenza antigenic point-of-care (POC) tests are too insensitive for individual reliable diagnosis of influenza virus infections without additional laboratory confirmation. Molecular POC tests could be a valuable alternative. Objectives To evaluate the first influenza molecular POC test commercially available, the Cepheid Xpert Flu A Panel designed to simultaneously detect influenza A virus and subtype A(H1N1) 2009 pandemic virus, and compare it with in-house real-time RT-PCR (qRT-PCR). Study design Clinical specimens positive for influenza virus and influenza virus isolates with different viral loads and of different type and subtype were used to determine the analytical reactivity and sensitivity. A panel of pathogen negative specimens and isolates of 19 different respiratory pathogens were used to determine the analytical specificity. Results Except A(H9N2) virus the Xpert Flu A Panel detected A(H1N1) seasonal and 2009 pandemic, A(H3N2), A(H5N2), A(H5N1) and A(H7N7) viruses and correctly subtyped A(H1N1) 2009 virus. Analytical sensitivity was similar to qRT-PCR in the range of 400–5000 viral particles per ml. However, of most subtypes some specimens with cycle threshold values greater than 30 in qRT-PCR and A(H1N1) 2009 specimens with inconsistent results in the qRT-PCR due to primer or probe mismatches were not detected in the Xpert Flu A Panel. Analytical specificity was 100%. Conclusions The Xpert Flu A Panel is the first commercially available POC molecular test for detection of influenza A virus and determination of the H1 2009 subtype and is analytically reasonable sensitive compared with qRT-PCR and highly specific and therefore a welcome alternative to antigenic POC tests.

negative: Physical interventions to interrupt or reduce the spread of respiratory viruses. BACKGROUND Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a global threat. Antiviral drugs and vaccinations may be insufficient to prevent their spread. OBJECTIVES To review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. SEARCH STRATEGY We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3), which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to October 2010), OLDMEDLINE (1950 to 1965), EMBASE (1990 to October 2010), CINAHL (1982 to October 2010), LILACS (2008 to October 2010), Indian MEDLARS (2008 to October 2010) and IMSEAR (2008 to October 2010). SELECTION CRITERIA In this update, two review authors independently applied the inclusion criteria to all identified and retrieved articles and extracted data. We scanned 3775 titles, excluded 3560 and retrieved full papers of 215 studies, to include 66 papers of 67 studies. We included physical interventions (screening at entry ports, isolation, quarantine, social distancing, barriers, personal protection, hand hygiene) to prevent respiratory virus transmission. We included randomised controlled trials (RCTs), cohorts, case-controls, before-after and time series studies. DATA COLLECTION AND ANALYSIS We used a standardised form to assess trial eligibility. We assessed RCTs by randomisation method, allocation generation, concealment, blinding and follow up. We assessed non-RCTs for potential confounders and classified them as low, medium and high risk of bias. MAIN RESULTS We included 67 studies including randomised controlled trials and observational studies with a mixed risk of bias. A total number of participants is not included as the total would be made up of a heterogenous set of observations (participant people, observations on participants and countries (object of some studies)). The risk of bias for five RCTs and most cluster-RCTs was high. Observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis. The highest quality cluster-RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Benefit from reduced transmission from children to household members is broadly supported also in other study designs where the potential for confounding is greater. Nine case-control studies suggested implementing transmission barriers, isolation and hygienic measures are effective at containing respiratory virus epidemics. Surgical masks or N95 respirators were the most consistent and comprehensive supportive measures. N95 respirators were non-inferior to simple surgical masks but more expensive, uncomfortable and irritating to skin. Adding virucidals or antiseptics to normal handwashing to decrease respiratory disease transmission remains uncertain. Global measures, such as screening at entry ports, led to a non-significant marginal delay in spread. There was limited evidence that social distancing was effective, especially if related to the risk of exposure. AUTHORS' CONCLUSIONS Simple and low-cost interventions would be useful for reducing transmission of epidemic respiratory viruses. Routine long-term implementation of some measures assessed might be difficult without the threat of an epidemic.

negative: Pathogenesis of feline enteric coronavirus infection Fifty-one specific pathogen-free (SPF) cats 10 weeks to 13 years of age were infected with a cat-to-cat fecal–oral passed strain of feline enteric coronavirus (FECV). Clinical signs ranged from unapparent to a mild and self-limiting diarrhea. Twenty-nine of these cats were FECV naïve before infection and followed sequentially for fecal virus shedding and antibody responses over a period of 8–48 months. Fecal shedding, as determined by real-time polymerase chain reaction (RT-PCR) from rectal swabs, appeared within a week and was significantly higher in kittens than older cats. FECV shedding remained at high levels for 2–10 months before eventually evolving into one of three excretion patterns. Eleven cats shed the virus persistently at varying levels over an observation period of 9–24 months. Eleven cats appeared to have periods of virus shedding interlaced with periods of non-shedding (intermittent or recurrent shedders), and seven cats ceased shedding after 5–19 months (average 12 months). There was no change in the patterns of virus shedding among cats that were excreting FECV at the time of a secondary challenge exposure. Four cats, which had ceased shedding, re-manifested a primary type infection when secondarily infected. Cats with higher feline coronavirus (FCoV) antibody titers were significantly more likely to shed virus, while cats with lower titers were significantly less likely to be shedding. Twenty-two kittens born to experimentally infected project queens began shedding virus spontaneously, but never before 9–10 weeks of age. Natural kittenhood infections appeared to be low grade and abortive. However, a characteristic primary type infection occurred following experimental infection with FECV at 12–15 weeks of age. Pregnancy, parturition and lactation had no influence on fecal shedding by queens. Methylprednisolone acetate treatment did not induce non-shedders to shed and shedders to increase shedding.

negative: EMERGING RESPIRATORY DISEASE - CORONAVIRUSES

negative: Preparedness of Residential and Nursing Homes for Pandemic Flu BACKGROUND: Work is being undertaken across a wide range of agencies to ensure a high level of preparedness for pandemic influenza. In England, the Department of Health has published a range of guidance to support this. The impact of pandemic flu on care homes, especially if unprepared may have a major knock on effect on the rest of the health and social care system. OBJECTIVE AND METHODS: A rapid survey was undertaken of a small number of care homes in West Yorkshire to assess preparedness. The homes were both local authority and privately owned. RESULTS: It was apparent that little preparation had been done at the time of the survey. A range of readily implementable ideas that may help this sector prepare was identified. CONCLUSION: Planning for pandemic flu in this sector will require effort and coordination across a range of sectors; it might best be coordinated through Local Resilience Forums.

negative: Update on Avian Influenza for Critical Care Physicians Human influenza pandemics over the last 100 years have been caused by H1, H2, and H3 subtypes of influenza A viruses. More recently, avian influenza viruses have been found to directly infect humans from their avian hosts. The recent emergence, host expansion, and spread of a highly pathogenic avian influenza (HPAI) H5N1 subtype in Asia has heightened concerns globally, both in regards to mortality of HPAI H5N1 in humans and the potential of a new pandemic. In response, many agencies and organizations have been working collaboratively to develop early detection systems, preparedness plans, and objectives for further research. As a result, there has been a large influx of published information regarding potential risk, surveillance, prevention and control of highly pathogenic avian influenza, particularly in regards to animal to human and subsequent human to human transmission. This chapter will review the current human infections with avian influenza and its public health and medical implications.

negative: Agent-based simulation for weekend-extension strategies to mitigate influenza outbreaks BACKGROUND: Non-pharmaceutical strategies are vital in curtailing impacts of influenza and have been intensively studied in public health. However, few strategies have explicitly utilized the weekend effect, which has been widely reported to be capable of reducing influenza infections. This study aims to explore six weekend-extension strategies against seasonal and pandemic flu outbreaks. METHODS: The weekend-extension strategies were designed to extend regular two-day weekend by one, two and three days, respectively, and in combination with either a continuous or discontinuous pattern. Their effectiveness was evaluated using an established agent-based spatially explicit simulation model in the urbanized area of Buffalo, NY, US. RESULTS: If the extensions last more than two days, the weekend-extension strategies can remarkably reduce the overall disease attack rate of seasonal flu. Particularly, a three-day continuous extension is sufficient to suppress the epidemic and confine the spread of disease. For the pandemic flu, the weekend-extension strategies only produce a few mitigation effects until the extensions exceed three days. Sensitivity analysis indicated that a compliance level above 75% is necessary for the weekend-extension strategies to take effects. CONCLUSION: This research is the first attempt to incorporate the weekend effect into influenza mitigation strategies. The results suggest that appropriate extensions of the regular two-day weekend can be a potential measure to fight against influenza outbreaks, while minimizing interruptions on normal rhythms of socio-economy. The concept of weekend extension would be particularly useful if there were a lack of vaccine stockpiles, e.g., in countries with limited health resources, or in the case of unknown emerging infectious diseases.

negative: Seasonality of infectious diseases and severe acute respiratory syndrome–what we don't know can hurt us Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.

negative: Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV) The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

negative: Joint Prediction and Time Estimation of COVID-19 Developing Severe Symptoms using Chest CT Scan With the rapidly worldwide spread of Coronavirus disease (COVID-19), it is of great importance to conduct early diagnosis of COVID-19 and predict the time that patients might convert to the severe stage, for designing effective treatment plan and reducing the clinicians' workloads. In this study, we propose a joint classification and regression method to determine whether the patient would develop severe symptoms in the later time, and if yes, predict the possible conversion time that the patient would spend to convert to the severe stage. To do this, the proposed method takes into account 1) the weight for each sample to reduce the outliers' influence and explore the problem of imbalance classification, and 2) the weight for each feature via a sparsity regularization term to remove the redundant features of high-dimensional data and learn the shared information across the classification task and the regression task. To our knowledge, this study is the first work to predict the disease progression and the conversion time, which could help clinicians to deal with the potential severe cases in time or even save the patients' lives. Experimental analysis was conducted on a real data set from two hospitals with 422 chest computed tomography (CT) scans, where 52 cases were converted to severe on average 5.64 days and 34 cases were severe at admission. Results show that our method achieves the best classification (e.g., 85.91% of accuracy) and regression (e.g., 0.462 of the correlation coefficient) performance, compared to all comparison methods. Moreover, our proposed method yields 76.97% of accuracy for predicting the severe cases, 0.524 of the correlation coefficient, and 0.55 days difference for the converted time.

negative: Development and verification of real-time PCR assay for identification of viral agents causing acute respiratory infections in human beings A multiplex polymerase chain reaction (PCR) for identification of four viruses causing acute respiratory diseases in human beings was developed. The analytical sensitivity of developed RT-PCR for identification of adenovirus, respiratory-syncytial virus, flu viruses types A and B, and actual subtypes of type A flu virus (seasonal and pandemic variants H1N1, seasonal H3N2, and viruses of bird flu that are pathogenic to human beings H5 and H7) was 1 × 10(3) genome equivalents per milliliter. Diagnostic sensitivity for flu virus type A and B, and also subtypes H1 (seasonal H1N1, pandemic variant of H1N1 of year 2009), H3, H5 was 1 × 10(3)–10(4) viral particles per milliliter. The method developed has high specificity and does not have positive signal in experiments with DNA/cDNA of human beings and viral DNA. We have studied 50 samples using the developed set. Etiology was defined in 33 samples.

negative: COVID-19: towards controlling of a pandemic

negative: Avian Flu – A Bird's Eye View Influenza A (H5N1) virus infects a variety of animals, birds and humans. Present ongoing epidemic of this deadly virus in poultry livestock and humans has had major economic and health repercussions. It causes a wide spectrum of clinical features in human beings ranging from mild respiratory tract infection to a fatal pneumonia leading to multi organ system failure. Diagnosis is mainly clinical, aided by lab features like lymphopaenia and non-specific chest X-ray findings. Diagnostic tests are being evolved for rapid and specific diagnosis. Management is mainly symptomatic. Newer and effective antivirals, i.e. amantadine, zanamivir etc are also being tried.

negative: Frequency of diarrhea in novel coronavirus 2019 infection

negative: Perceived Threat, Risk Perception, and Efficacy Beliefs Related to SARS and Other (Emerging) Infectious Diseases: Results of an International Survey PURPOSE: To study the levels of perceived threat, perceived severity, perceived vulnerability, response efficacy, and self-efficacy for severe acute respiratory syndrome (SARS) and eight other diseases in five European and three Asian countries. METHOD: A computer-assisted phone survey was conducted among 3,436 respondents. The questionnaire focused on perceived threat, vulnerability, severity, response efficacy, and self-efficacy related to SARS and eight other diseases. RESULTS: Perceived threat of SARS in case of an outbreak in the country was higher than that of other diseases. Perceived vulnerability of SARS was at an intermediate level and perceived severity was high compared to other diseases. Perceived threat for SARS varied between countries in Europe and Asia with a higher perceived severity of SARS in Europe and a higher perceived vulnerability in Asia. Response efficacy and self-efficacy for SARS were higher in Asia compared to Europe. In multiple linear regression analyses, country was strongly associated with perceived threat. CONCLUSIONS: The relatively high perceived threat for SARS indicates that it is seen as a public health risk and offers a basis for communication in case of an outbreak. The strong association between perceived threat and country and different regional patterns require further research.

negative: Excess cases of Influenza like illnesses in France synchronous with COVID19 invasion. Several French regions where COVID19 has been reported currently show a renewed increase in ILI cases in the general practice based Sentinelles network. Here we computed the number of excess cases by region and found correlation with the number of reported COVID19 cases so far. These data suggest larger circulation of SARS-CoV-2 in the French population than apparent from confirmed cases.

negative: Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

negative: Comparisons of substitution, insertion and deletion probes for resequencing and mutational analysis using oligonucleotide microarrays Although oligonucleotide probes complementary to single nucleotide substitutions are commonly used in microarray-based screens for genetic variation, little is known about the hybridization properties of probes complementary to small insertions and deletions. It is necessary to define the hybridization properties of these latter probes in order to improve the specificity and sensitivity of oligonucleotide microarray-based mutational analysis of disease-related genes. Here, we compare and contrast the hybridization properties of oligonucleotide microarrays consisting of 25mer probes complementary to all possible single nucleotide substitutions and insertions, and one and two base deletions in the 9168 bp coding region of the ATM (ataxia telangiectasia mutated) gene. Over 68 different dye-labeled single-stranded nucleic acid targets representing all ATM coding exons were applied to these microarrays. We assess hybridization specificity by comparing the relative hybridization signals from probes perfectly matched to ATM sequences to those containing mismatches. Probes complementary to two base substitutions displayed the highest average specificity followed by those complementary to single base substitutions, single base deletions and single base insertions. In all the cases, hybridization specificity was strongly influenced by sequence context and possible intra- and intermolecular probe and/or target structure. Furthermore, single nucleotide substitution probes displayed the most consistent hybridization specificity data followed by single base deletions, two base deletions and single nucleotide insertions. Overall, these studies provide valuable empirical data that can be used to more accurately model the hybridization properties of insertion and deletion probes and improve the design and interpretation of oligonucleotide microarray-based resequencing and mutational analysis.

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

negative: The global battle against SARS-CoV-2 and COVID-19

negative: Years of life lost due to the psychosocial consequences of COVID19 mitigation strategies based on Swiss data Background: The pandemic caused by COVID-19 has forced governments to implement strict social mitigation strategies to reduce the acute morbidity and mortality from acute infections. These strategies however carry a significant risk for mental health which can lead to increased short-term and long-term mortality, which is currently not included in modelling the impact of the pandemic. Methods: We used years of life lost (YLL) as the main outcome measure as applied to Switzerland as an exemplar. We focused on suicide, depression, alcohol use disorder, childhood physical abuse and social isolation as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We also estimated a minimum duration of mitigation of 3 months based on current public health plans. Results: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by a subpopulation of 2.1 percent of the population, the average of whom suffer an average 9.79 YLL. Conclusions: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, model like the one presented here highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

negative: Dynamic causal modelling of COVID-19 This technical report describes a dynamic causal model of the spread of coronavirus through a population. The model is based upon ensemble or population dynamics that generate outcomes, like new cases and deaths over time. The purpose of this model is to quantify the uncertainty that attends predictions of relevant outcomes. By assuming suitable conditional dependencies, one can model the effects of interventions (e.g., social distancing) and differences among populations (e.g., herd immunity) to predict what might happen in different circumstances. Technically, this model leverages state-of-the-art variational (Bayesian) model inversion and comparison procedures, originally developed to characterise the responses of neuronal ensembles to perturbations. Here, this modelling is applied to epidemiological populations to illustrate the kind of inferences that are supported and how the model per se can be optimised given timeseries data. Although the purpose of this paper is to describe a modelling protocol, the results illustrate some interesting perspectives on the current pandemic; for example, the nonlinear effects of herd immunity that speak to a self-organised mitigation process.

negative: Influenza Influenza, briefly known as flu, is an acute respiratory infectious disease caused by influenza virus. It spreads via droplets, with strong infectivity. Its incident rate ranks first in legal infectious diseases, with occurrences of outbreaks or pandemics. Its clinical symptoms are characterized by acute onset of high fever, fatigue, systemic muscular soreness and pain, as well as mild respiratory tract symptoms. Influenza more commonly occurs in autumns and winters. Although it has a short disease course and is self-limited, it may be complicated by pneumonia and other serious complications in populations including the elderly, infants and young children, patients with cardiac or pulmonary diseases, patients with other chronic diseases, and patients with compromised immunity. In some serious cases, death may even occur.

negative: Genomic Epidemiology and its importance in the study of the COVID-19 pandemic. Not available.

negative: Self-other differences in H1N1 flu risk perception in a global context: a comparative study between the United States and China. Extending research on self-other differences in perception to a global health risk, this study compares U.S. and Chinese college students' perceived H1N1 flu risk at four levels: personal, group, societal, and global. It also examines how personal experience, interpersonal communication, traditional and Internet-based media, and self-efficacy affect perception at four levels, as well as the self-other differences between the personal level and each of the other three levels. An online survey in both countries reveals an "ascending pattern," showing higher perceived risk for others than for selves. Chinese respondents perceive higher risk than U.S. respondents at all levels. Interpersonal communication predicts risk perception at four levels in the United States and at the group and societal levels in China. New media exposure exerts influence on all but the group level in China, while social networking sites (SNS) exposure predicts group- and societal-level risk perception in the United States. The overall attention paid to H1N1 information in the media affects all levels in both countries. Interaction between media exposure and attention is influential at all levels in the United States. Self-efficacy is negatively associated with risk perception in China except at the global level. Attention to media in the United States, and SNS exposure in China, explain the self-other differences in three comparisons, along with self-efficacy, which decreases the self-other gap in the United States while increasing the gap in China.

negative: More effective strategies are required to strengthen public awareness of COVID-19: Evidence from Google Trends BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has posed stress on the health and well-being of both Chinese people and the public worldwide. Global public interest in this new issue largely reflects people’s attention to COVID-19 and their willingness to take precautionary actions. This study aimed to examine global public awareness of COVID-19 using Google Trends. METHODS: Using Google Trends, we retrieved public query data for terms of “2019-nCoV + SARS-CoV-2 + novel coronavirus + new coronavirus + COVID-19 + Corona Virus Disease 2019” between the 31(st) December 2019 and the 24(th) February 2020 in six major English-speaking countries, including the USA, the UK, Canada, Ireland, Australia, and New Zealand. Dynamic series analysis demonstrates the overall change trend of relative search volume (RSV) for the topic on COVID-19. We compared the top-ranking related queries and sub-regions distribution of RSV about COVID-19 across different countries. The correlation between daily search volumes on the topic related to COVID-19 and the daily number of people infected with SARS-CoV-2 was analyzed. RESULTS: The overall search trend of RSV regarding COVID-19 increased during the early period of observing time and reached the first apex on 31(st) January 2020. A shorter response time and a longer duration of public attention to COVID-19 was observed in public from the USA, the UK, Australia, and Canada, than that in Ireland and New Zealand. A slightly positive correlation between daily RSV about COVID-19 and the daily number of confirmed cases was observed (P < 0.05). People across countries presented a various interest to the RSV on COVID-19, and public awareness of COVID-19 was different in various sub-regions within countries. CONCLUSIONS: The results suggest that public response time to COVID-19 was different across countries, and the overall duration of public attention was short. The current study reminds us that governments should strengthen the publicity of COVID-19 nationally, strengthen the public's vigilance and sensitivity to COVID-19, inform public the importance of protecting themselves with enough precautionary measures, and finally control the spread of COVID-19 globally.

negative: Field Effectiveness of Pandemic and 2009-2010 Seasonal Vaccines against 2009-2010 A(H1N1) Influenza: Estimations from Surveillance Data in France BACKGROUND: In this study, we assess how effective pandemic and trivalent 2009-2010 seasonal vaccines were in preventing influenza-like illness (ILI) during the 2009 A(H1N1) pandemic in France. We also compare vaccine effectiveness against ILI versus laboratory-confirmed pandemic A(H1N1) influenza, and assess the possible bias caused by using non-specific endpoints and observational data. METHODOLOGY AND PRINCIPAL FINDINGS: We estimated vaccine effectiveness by using the following formula: VE = (PPV-PCV)/(PPV(1-PCV)) × 100%, where PPV is the proportion vaccinated in the population and PCV the proportion of vaccinated influenza cases. People were considered vaccinated three weeks after receiving a dose of vaccine. ILI and pandemic A(H1N1) laboratory-confirmed cases were obtained from two surveillance networks of general practitioners. During the epidemic, 99.7% of influenza isolates were pandemic A(H1N1). Pandemic and seasonal vaccine uptakes in the population were obtained from the National Health Insurance database and by telephonic surveys, respectively. Effectiveness estimates were adjusted by age and week. The presence of residual biases was explored by calculating vaccine effectiveness after the influenza period. The effectiveness of pandemic vaccines in preventing ILI was 52% (95% confidence interval: 30–69) during the pandemic and 33% (4–55) after. It was 86% (56–98) against confirmed influenza. The effectiveness of seasonal vaccines against ILI was 61% (56–66) during the pandemic and 19% (−10–41) after. It was 60% (41–74) against confirmed influenza. CONCLUSIONS: The effectiveness of pandemic vaccines in preventing confirmed pandemic A(H1N1) influenza on the field was high, consistently with published findings. It was significantly lower against ILI. This is unsurprising since not all ILI cases are caused by influenza. Trivalent 2009-2010 seasonal vaccines had a statistically significant effectiveness in preventing ILI and confirmed pandemic influenza, but were not better in preventing confirmed pandemic influenza than in preventing ILI. This lack of difference might be indicative of selection bias.

negative: Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs) are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV) and human bocavirus (HBoV). 157 of the 981 (16.0%) nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%), OC43 (42 cases, 4.3%), HKU1 (16 cases, 1.6%) and NL63 (11 cases, 1.1%). HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003), and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03). 48 of 157(30.57%) HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu) A were the most common viruses detected (more than 35%) in HCoV co-infections. Respiratory syncytial virus (RSV), human parainfluenza virus (PIV) and HBoV were detected in very low rate (less than 1%) among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.

negative: COVID-19: the gendered impacts of the outbreak

negative: Can Testing Ease Social Distancing Measures? Future Evolution of COVID-19 in NYC The"New York State on Pause"executive order came into effect on March 22 with the goal of ensuring adequate social distancing to alleviate the spread of COVID-19. Pause will remain effective in New York City in some form until early June. We use a compartmentalized model to study the effects of testing capacity and social distancing measures on the evolution of the pandemic in the"post-Pause"period in the City. We find that testing capacity must increase dramatically if it is to counterbalance even relatively small relaxations in social distancing measures in the immediate post-Pause period. In particular, if the City performs 20,000 tests per day and relaxes the social distancing measures to the pre-Pause norms, then the total number of deaths by the end of September can reach 250,000. By keeping the social distancing measures to somewhere halfway between the pre- and in-Pause norms and performing 100,000 tests per day, the total number of deaths by the end of September can be kept at around 27,000. Going back to the pre-Pause social distancing norms quickly must be accompanied by an exorbitant testing capacity, if one is to suppress excessive deaths. If the City is to go back to the"pre-Pause"social distancing norms in the immediate post-Pause period and keep the total number of deaths by the end of September at around 35,000, then it should be performing 500,000 tests per day. Our findings have important implications on the magnitude of the testing capacity the City needs as it relaxes the social distancing measures to reopen its economy.

negative: Ensuring Effective and Quality Care During a Pandemic

negative: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 Abstract SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.

negative: COVID-19 Pandemic and Impending Global Mental Health Implications The increase in organisms transference and infectious pandemics across the globe have been accelerated by an increase in travel, international exchange and global changes in earth's climate. COVID-19, a virus caused by the novel coronavirus that was initially identified on December 2019, in Wuhan city of China is currently affecting 146 territories, states and countries raising distress, panic and increasing anxiety in individuals exposed to the (actual or supposed) peril of the virus across the globe. Fundamentally, these concerns ascend with all infections, including those of flu and other agents, and the same worldwide safeguards are compulsory and suggested for protection and the prevention of further diffusion. However, media has underlined COVID-19 as rather an exclusive threat, which has added to panic and stress in masses which can lead to several mental health issues like anxiety, obsessive compulsive disorder and post-traumatic stress disorder which should be contained immediately in its initial phases.

negative: Lung Ultrasound and the COVID‐19 “Pattern”: Not All That Glitters Today Is Gold Tomorrow

negative: Influenza A Virus Infections in Dromedary Camels, Nigeria and Ethiopia, 2015–2017 We examined nasal swabs and serum samples acquired from dromedary camels in Nigeria and Ethiopia during 2015–2017 for evidence of influenza virus infection. We detected antibodies against influenza A(H1N1) and A(H3N2) viruses and isolated an influenza A(H1N1)pdm09–like virus from a camel in Nigeria. Influenza surveillance in dromedary camels is needed.

negative: The role of the radiologist in diagnosing the COVID-19 infection. Parma experiences The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the coronavirus disease 2019 (COVID-19), a respiratory disease that ranges from an asymptomatic or mild flu-like illness to severe pneumonia, multiorgan failure, and death. Imaging might play an important role in clinical decision making by supporting rapid triage of patients with suspected COVID-19 and assessing supervening complications, such as super-added bacterial infection and thrombosis. Further studies will clarify the real impact of imaging on COVID-19 patients' management and the potential role of radiology in future outbreaks.

negative: Human Coronaviruses: General Features Abstract Human coronaviruses (HCoVs), including HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, are traditionally known to cause symptoms of common cold with only moderate clinical impact. Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), on the other hand, have strike humans in the past two decades as highly fatal human pathogens leading to considerable mortality and economic loss. This article summaries the updates on the structure, genome organization, replication and clinical features of human coronaviruses. Recent studies also shed light upon the zoonotic origin of emerging human pathogens including SARS-CoV and MERS-CoV, providing insight for future surveillance and intervention.

negative: Prevention and Control of Influenza Viruses The 2003–2004 outbreaks of highly pathogenic avian influenza (HPAI) have proven to be disastrous to the regional poultry industry in Asia, and have raised serious worldwide public health apprehension regarding the steps that should be taken to urgently control HPAI. Control measures must be taken based on the principles of biosecurity and disease management and at the same time making public aware of the precautionary measures at the verge of outbreak. Creation of protection and surveillance zones, various vaccination strategies viz. routine, preventive, emergency, mass and targeted vaccination programmes using live, inactivated and recombinant vaccines are the common strategies adopted in different parts of the globe. The new generation vaccines include recombinant vaccines and recombinant fusion vaccine. The pro-poor disease control programmes, giving compensation and subsidies to the farmers along with effective and efficient Veterinary Services forms integral part of control of HPAI. Following biosecurity principles and vaccination forms integral part of control programme against swine and equine influenza as well. Use of neuraminidase (NA) inhibitors (Zanamivir and Oseltamivir) for the treatment of human influenza has been widely accepted worldwide. The threat of increasing resistance of the flu viruses to these antivirals has evoked interest in the development of novel antiviral drugs for influenza virus such as inhibitors of cellular factors and host signalling cascades, cellular miRNAs, siRNA and innate immune peptides (defensins and cathelicidins). Commercial licensed inactivated vaccines for humans against influenza A and B viruses are available consisting of three influenza viruses: influenza type A subtype H3N2, influenza type A subtype H1N1 (seasonal) virus strain and influenza type B virus strain. As per WHO, use of tetravaccine consisting of antigens of influenza virus serotypes H3N2, H1N1, B and H5 is the most promising method to control influenza pandemic. All healthy children in many countries are required to be vaccinated between 6 and 59 months of age. The seasonal vaccines currently used in humans induce strain-specific humoral immunity as the antibodies. Universal influenza virus vaccines containing the relatively conserved ectodomain of M2 (M2e), M1, HA fusion peptide and stalk domains, NA, NP alone or in combination have been developed which have been shown to induce cross-protection. The T cell-based vaccines are another recent experimental approach that has been shown to elicit broad-spectrum heterosubtypic immunity in the host. As far as HPAI is concerned, various pandemic preparedness strategies have been documented.

negative: Airborne Influenza A Virus Exposure in an Elementary School Influenza contributes significantly to childhood morbidity and mortality. Given the magnitude of the school-aged child population, a sizeable proportion of influenza virus transmission events are expected to occur within school settings. However, influenza virus activity in schools is not well-understood, likely due to our limited ability to accurately monitor for respiratory viruses without disrupting the school environment. In this study, we evaluated the use of a bioaerosol sampling method to noninvasively detect and quantify airborne influenza A virus (IAV) densities in a public elementary school. Air samples were collected from multiple locations in the school, two days per week, throughout an eight-week sampling period during influenza season. Real-time RT-PCR targeting the IAV M gene revealed detectable IAV on five occasions in densities ranging from 2.0 × 10(−1) to 1.9 × 10(4). No significant differences in IAV densities were related to student presence/absence. The majority of IAV-associated particles were ≤4 μm in diameter, and theoretical calculations indicate infectious thresholds after minutes of exposure. Our study represents the first identification and quantification of airborne influenza virus in an elementary school, and the results suggest that airborne IAV has the potential to circulate in schools during influenza season, in large enough doses known to cause infection.

negative: Mental Health of Clinical Staff Working in High-Risk Epidemic and Pandemic Health Emergencies: A Rapid Review of the Evidence and Meta-Analysis The global pandemic of SARS-CoV-2 / COVID-19 has raised concerns about the potential mental health impact on frontline clinical staff. However, given that poor mental health is common in staff working in acute medicine, we aimed to estimate the additional burden of working directly with infected patients during epidemic and pandemic health emergencies. We completed a rapid review of the evidence and identified 74 relevant studies from outbreaks of COVID-19, Ebola, H1N1 influenza, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS). Due to varying caseness criteria, a meta-analysis of prevalence was not possible. However, it was clear that levels of self-reported depression, anxiety and posttraumatic stress disorder (PTSD) related symptoms were high, and somewhat higher in clinical staff working in high exposure roles. To assess the impact of high- versus low-exposure healthcare work more formally, we estimated the standardised mean difference (SMD) of scale means using a random effects meta-analysis. High exposure work was associated with only a small additional burden of acute mental health problems compared to low exposure work (anxiety: SMD=0.22, 95% CI 0.06 - 0.38; PTSD symptoms: SMD=0.21, 95% CI 0.01 - 0.4; depression: SMD=0.20, -0.07 - 0.47). This effect was potentially inflated by publication bias and there was a moderate risk of bias in the studies in the meta-analysis. A narrative review of candidate risk factors identified being a nurse, seeing colleagues infected, experiencing quarantine, non-voluntary role assignment, and experiencing stigma, as associated with particularly poor mental health outcomes. Protective factors included team and institutional support, use and faith in infection prevention measures, and a sense of professional duty and altruistic acceptance of risk. Notably, formal psychological support services were valued by frontline staff, although those with the highest burden of mental health difficulties were the least likely to request or receive support.

negative: Implications of public understanding of avian influenza for fostering effective risk communication. Avian influenza has three of the four properties necessary to cause a pandemic. However, are we as individuals and communities prepared for a pandemic flu in the United States? To help answer this question, 12 focus groups (N = 60) were conducted in Tulsa, Oklahoma, to determine the level of awareness of avian and pandemic flu for the county health department to develop effective communication messages. The overall findings indicate that the general Tulsa public lacks information about avian influenza or pandemics, does not believe a pandemic will occur, and believes if one does occur the government will take care of it. Finally, the groups agreed that education would be the key to preventing widespread panic if a pandemic occurred. Five themes emerged: confusion about terminology, seriousness of avian influenza, disaster fatigue, appropriate precautions, and credibility of health information. Each should be considered in developing effective risk communication messages.

negative: Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses Of the Orthomyxoviridae family of viruses, only influenza A viruses are thought to exist as multiple subtypes and has non-human maintenance hosts. In April 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. Subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven RNA segments exhibiting approximately 50% overall amino acid identity to human influenza C virus. Based on its genetic organizational similarities to influenza C viruses this virus has been provisionally designated C/Oklahoma/1334/2011 (C/OK). Phylogenetic analysis of the predicted viral proteins found that the divergence between C/OK and human influenza C viruses was similar to that observed between influenza A and B viruses. No cross reactivity was observed between C/OK and human influenza C viruses using hemagglutination inhibition (HI) assays. Additionally, screening of pig and human serum samples found that 9.5% and 1.3%, respectively, of individuals had measurable HI antibody titers to C/OK virus. C/OK virus was able to infect both ferrets and pigs and transmit to naive animals by direct contact. Cell culture studies showed that C/OK virus displayed a broader cellular tropism than a human influenza C virus. The observed difference in cellular tropism was further supported by structural analysis showing that hemagglutinin esterase (HE) proteins between two viruses have conserved enzymatic but divergent receptor-binding sites. These results suggest that C/OK virus represents a new subtype of influenza C viruses that currently circulates in pigs that has not been recognized previously. The presence of multiple subtypes of co-circulating influenza C viruses raises the possibility of reassortment and antigenic shift as mechanisms of influenza C virus evolution.

negative: Impact of climate and public health interventions on the COVID-19 pandemic: a prospective cohort study BACKGROUND: It is unclear whether seasonal changes, school closures or other public health interventions will result in a slowdown of the current coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine whether epidemic growth is globally associated with climate or public health interventions intended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We performed a prospective cohort study of all 144 geopolitical areas worldwide (375 609 cases) with at least 10 COVID-19 cases and local transmission by Mar. 20, 2020, excluding China, South Korea, Iran and Italy. Using weighted random-effects regression, we determined the association between epidemic growth (expressed as ratios of rate ratios [RRR] comparing cumulative counts of COVID-19 cases on Mar. 27, 2020, with cumulative counts on Mar. 20, 2020) and latitude, temperature, humidity, school closures, restrictions of mass gatherings, and measures of social distancing during an exposure period 14 days previously (Mar. 7 to 13, 2020). RESULTS: In univariate analyses, there were no associations of epidemic growth with latitude and temperature, but weak negative associations with relative humidity (RRR per 10% 0.91, 95% confidence interval [CI] 0.85-0.96) and absolute humidity (RRR per 5 g/m3 0.92, 95% CI 0.85-0.99). Strong associations were found for restrictions of mass gatherings (RRR 0.65, 95% CI 0.53-0.79), school closures (RRR 0.63, 95% CI 0.52-0.78) and measures of social distancing (RRR 0.62, 95% CI 0.45-0.85). In a multivariable model, there was a strong association with the number of implemented public health interventions (p for trend = 0.001), whereas the association with absolute humidity was no longer significant. INTERPRETATION: Epidemic growth of COVID-19 was not associated with latitude and temperature, but may be associated weakly with relative or absolute humidity. Conversely, public health interventions were strongly associated with reduced epidemic growth.

negative: COVID-19 and digital inequalities: Reciprocal impacts and mitigation strategies With more than three billion people in isolation, the status of digital spaces is switching from an amenity to a necessity, as they become not only the main way to access information and services, but also one of the only remaining vectors for economic, educational, and leisure activities as well as for social interactions to take place. However, not all are equals in terms of access to networks or connected devices, or when it comes to the skills required to navigate computerized spaces optimally. Digital inequalities were already existing, yet the COVID-19 crisis is exacerbating them dramatically. On the one hand, the crisis will worsen digital inequalities within the population. On the other hand, digital inequalities represent a major risk factor of vulnerability for exposure to the virus itself, and for the non-sanitary consequences of the crisis. Therefore, this paper aims at exploring the reciprocal impacts of the COVID-19 crisis and digital inequalities, and to propose operative solutions to help fight the nefarious consequences of the crisis. We first describe how digital inequalities are a determinant of health. We then investigate how COVID-19 can potentiate digital inequalities, and how digital inequalities potentiate vulnerability to COVID-19. Finally, in order to contribute to the mitigation of this crisis, we propose a set of multi-layered strategies focusing on actionability that can be implemented at multiple structural levels, ranging from governmental to corporate and community levels.

negative: Genetic and antigenic characterization of H5 and H7 avian influenza viruses isolated from migratory waterfowl in Mongolia from 2017 to 2019 The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public health. Migratory waterfowls play important roles in the transmission of these viruses across countries. To monitor virus spread by wild birds, active surveillance for avian influenza in migratory waterfowl was conducted in Mongolia from 2015 to 2019. In total, 5000 fecal samples were collected from lakesides in central Mongolia, and 167 influenza A viruses were isolated. Two H5N3, four H7N3, and two H7N7 viruses were characterized in this study. The amino acid sequence at hemagglutinin (HA) cleavage site of those isolates suggested low pathogenicity in chickens. Phylogenetic analysis revealed that all H5 and H7 viruses were closely related to recent H5 and H7 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds in Asia and Europe. Antigenicity of H7Nx was similar to those of typical non-pathogenic avian influenza viruses (AIVs). While HPAIVs or A/Anhui/1/2013 (H7N9)-related LPAIVs were not detected in migratory waterfowl in Mongolia, sporadic introductions of AIVs including H5 and H7 viruses into Mongolia through the wild bird migration were identified. Thus, continued monitoring of H5 and H7 AIVs in both domestic and wild birds is needed for the early detection of HPAIVs spread into the country. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-020-01764-2) contains supplementary material, which is available to authorized users.

negative: SARS-CoV ORF1b-encoded nonstructural proteins 12–16: Replicative enzymes as antiviral targets Abstract The SARS (severe acute respiratory syndrome) pandemic caused ten years ago by the SARS-coronavirus (SARS-CoV) has stimulated a number of studies on the molecular biology of coronaviruses. This research has provided significant new insight into many mechanisms used by the coronavirus replication-transcription complex (RTC). The RTC directs and coordinates processes in order to replicate and transcribe the coronavirus genome, a single-stranded, positive-sense RNA of outstanding length (∼27–32kilobases). Here, we review the up-to-date knowledge on SARS-CoV replicative enzymes encoded in the ORF1b, i.e., the main RNA-dependent RNA polymerase (nsp12), the helicase/triphosphatase (nsp13), two unusual ribonucleases (nsp14, nsp15) and RNA-cap methyltransferases (nsp14, nsp16). We also review how these enzymes co-operate with other viral co-factors (nsp7, nsp8, and nsp10) to regulate their activity. These last ten years of research on SARS-CoV have considerably contributed to unravel structural and functional details of one of the most fascinating replication/transcription machineries of the RNA virus world. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10years of research on highly pathogenic human coronaviruses”.

negative: Necessity to critically review the automatic results of the Xpert Flu assay Abstract While using the Xpert Flu assay we became aware of false-negative results. The study aimed to analyze the causes of these false-negative results. One hundred fifty-nine respiratory specimens were tested in the Xpert Flu assay and in multiplex reverse transcription–polymerase chain reactions (RT-PCRs) for respiratory viruses. Discordant specimens were tested in the Influenza A/B r-gene assay. One hundred fifty-two (96%) and 151 (95%) specimens yielded concordant results for influenza A and B, respectively. Fifteen specimens tested negative in the Xpert Flu assay and positive in a multiplex RT-PCR. Positive results were confirmed for 12 of these specimens in the Influenza A/B r-gene assay. Xpert Flu assay amplification curves and endpoints suggested that the false-negative results were mainly due to erroneous automatic result interpretation. We report false-negative results of the Xpert Flu assay due to erroneous automatic result interpretation. Careful analysis of amplification curves and endpoints is needed to avoid reporting of false-negative results.

negative: Respiratory viruses are continuously detected in children with chronic tonsillitis throughout the year Abstract Objective To evaluate the oscillations on the viral detection in adenotonsillar tissues from patients with chronic adenotonsillar diseases as an indicia of the presence of persistent viral infections or acute subclinical infections. Study design Cross-sectional prospective study. Setting Tertiary hospital. Methods The fluctuations of respiratory virus detection were compared to the major climatic variables during a two-year period using adenoids and palatine tonsils from 172 children with adenotonsillar hypertrophy and clinical evidence of obstructive sleep apnoea syndrome or recurrent adenotonsillitis, without symptoms of acute respiratory infection (ARI), by TaqMan real-time PCR. Results The rate of detection of at least one respiratory virus in adenotonsillar tissue was 87%. The most frequently detected viruses were human adenovirus in 52.8%, human enterovirus in 47.2%, human rhinovirus in 33.8%, human bocavirus in 31.1%, human metapneumovirus in 18.3% and human respiratory syncytial virus in 17.2%. Although increased detection of human enterovirus occurred in summer/autumn months, and there were summer nadirs of human respiratory syncytial virus in both years of the study, there was no obvious viral seasonality in contrast to reports with ARI patients in many regions of the world. Conclusion Respiratory viruses are continuously highly detected during whole year, and without any clinical symptomatology, indicating that viral genome of some virus can persist in lymphoepithelial tissues of the upper respiratory tract.

negative: Estimation of basic reproduction number for COVID‐19 and the reasons for its differences The novel coronavirus pneumonia is an acute respiratory disease. In December 2019, this disease emerged in Wuhan, China. The Chinese government called it SARS‐CoV‐2 which was subsequently named COVID‐19 by the World Health Organization (WHO) [1]. In January 2020, WHO confirmed it as a sustained human to human disease [2]. By March 2020, COVID‐19 had been transmitted round the world rapidly and every day large number of new cases were registered. COVID‐19 is a leaped type of coronavirus family such as Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) that has been transmitted from wild animals to human [3].

negative: Managing neonates with respiratory failure due to SARS-CoV-2 – Authors' reply

negative: Declining Public Health Protections within Autocratic Regimes: Impact on Global Public Health Security, Infectious Disease Outbreaks, Epidemics, and Pandemics Public health emergencies of international concern, in the form of infectious disease outbreaks, epidemics, and pandemics, represent an increasing risk to the worldʼs population. Management requires coordinated responses, across many disciplines and nations, and the capacity to muster proper national and global public health education, infrastructure, and prevention measures. Unfortunately, increasing numbers of nations are ruled by autocratic regimes which have characteristically failed to adopt investments in public health infrastructure, education, and prevention measures to keep pace with population growth and density. Autocratic leaders have a direct impact on health security, a direct negative impact on health, and create adverse political and economic conditions that only complicate the crisis further. This is most evident in autocratic regimes where health protections have been seriously and purposely curtailed. All autocratic regimes define public health along economic and political imperatives that are similar across borders and cultures. Autocratic regimes are seriously handicapped by sociopathic narcissistic leaders who are incapable of understanding the health consequences of infectious diseases or the impact on their population. A cross section of autocratic nations currently experiencing the impact of COVID-19 (coronavirus disease 2019) are reviewed to demonstrate the manner where self-serving regimes fail to manage health crises and place the rest of the world at increasing risk. It is time to re-address the pre-SARS (severe acute respiratory syndrome) global agendas calling for stronger strategic capacity, legal authority, support, and institutional status under World Health Organization (WHO) leadership granted by an International Health Regulations Treaty. Treaties remain the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. “Honesty is worth a lot more than hope…” The Economist, February 17, 2020.

negative: COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells following binding with the cell surface ACE2 receptors, thereby leading to coronavirus disease 2019 (COVID-19). SARS-CoV-2 causes viral pneumonia with additional extrapulmonary manifestations and major complications, including acute myocardial injury, arrhythmia, and shock mainly in elderly patients. Furthermore, patients with existing cardiovascular comorbidities, such as hypertension and coronary heart disease, have a worse clinical outcome following contraction of the viral illness. A striking feature of COVID-19 pandemics is the high incidence of fatalities in advanced aged patients: this might be due to the prevalence of frailty and cardiovascular disease increase with age due to endothelial dysfunction and loss of endogenous cardioprotective mechanisms. Although experimental evidence on this topic is still at its infancy, the aim of this position paper is to hypothesize and discuss more suggestive cellular and molecular mechanisms whereby SARS-CoV-2 may lead to detrimental consequences to the cardiovascular system. We will focus on aging, cytokine storm, NLRP3/inflammasome, hypoxemia, and air pollution, which is an emerging cardiovascular risk factor associated with rapid urbanization and globalization. We will finally discuss the impact of clinically available CV drugs on the clinical course of COVID-19 patients. Understanding the role played by SARS-CoV2 on the CV system is indeed mandatory to get further insights into COVID-19 pathogenesis and to design a therapeutic strategy of cardio-protection for frail patients.

negative: Seasonal variation of respiratory pathogen colonization in asymptomatic health care professionals: A single-center, cross-sectional, 2-season observational study BACKGROUND: The purpose of this study was to determine the seasonal variance of potentially pathogenic bacterial and viral organisms in nasopharyngeal specimens obtained from asymptomatic health care professionals (HCPs) during the 2014 winter and summer months. METHODS: Nasopharyngeal specimens from 100 HCPs were collected from Huntsville Hospital (Huntsville, AL) during the winter and from 100 HCPs during the summer. All subjects were tested for 22 viruses and 19 bacteria using Target Enriched Multiplex Polymerase Chain Reaction. Both seasonal cohorts were composed of students, nurses, physicians, and residents. RESULTS: Of the 100 HCPs tested during the winter, 34 subjects were colonized with at least 1 bacterium, and 11 tested positive for at least 1 virus. Methicillin-resistant Staphylococcus aureus (MRSA), Moraxella catarrhalis, and coronavirus were the most frequently detected potentially infectious agents. Of the 100 HCPs tested during the summer, 37 tested positive for at least 1 bacterium, and 4 tested positive for a viral agent. The most prevalent bacteria were MRSA and Klebsiella pneumonia. CONCLUSION: Nasopharyngeal carriage among asymptomatic HCPs was common, but the frequency and presence of potential pathogens varied with each season. Understanding the colonization and infection potential of upper respiratory organisms is important, particularly for viruses. Although asymptomatic HCPs certainly harbor a number of different potentially infectious agents, future studies are needed to determine whether colonized pathogens are transmitted or initiate infection in at-risk patient populations.

negative: Otorhinolaryngologists and Coronavirus Disease 2019 (COVID-19)

negative: Avian Influenza: Should China Be Alarmed? Avian influenza has emerged as one of the primary public health concern of the 21st century. Influenza strain H5N1 is capable of incidentally infecting humans and other mammals. Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have been transmitted from poultry to humans (by direct or indirect contact with infected birds) in several provinces of Mainland China, which has resulted in 22 cases of human infection and has created repercussions for the Chinese economy. People have been concerned whether a new pandemic will occur in the future. The eradication of pathogenic avian influenza viruses appears to be the most effective way to prevent an influenza pandemic. This paper will examine the features of H5N1, including incidence, infection, immunity, clinical management, prevention and control, and therapy in Mainland China.

negative: National Governance of Public Health Responses in a Pandemic? The world is currently facing the worst pandemic in a century and we were caught unprepared. COVID-19 has proven highly contagious and with severe consequences that are still unfolding. As of 16 April 2020, there were over 2 million confirmed cases and over 136,000 related deaths reported worldwide. Over 1 million of those confirmed cases were in the preceding 14 days, with the USA accounting for nearly half of those. Furthermore, the International Monetary Fund (IMF) is now warning that the world is about to suffer the worst economic recession since the Great Depression in the 1920s.

negative: A Bibliometric Analysis of COVID-19 Research Activity: A Call for Increased Output Background: The novel coronavirus disease 2019 (COVID-19) has impacted many countries across all inhabited continents, and is now considered a global pandemic, due to its high rate of infectivity. Research related to this disease is pivotal for assessing pathogenic characteristics and formulating therapeutic strategies. The aim of this paper is to explore the activity and trends of COVID-19 research since its outbreak in December 2019. Methods: We explored the PubMed database and the World Health Organization (WHO) database for publications pertaining to COVID-19 since December 2019 up until March 18, 2020. Only relevant observational and interventional studies were included in our study. Data on COVID-19 incidence were extracted from the WHO situation reports. Research output was assessed with respect to gross domestic product (GDP) and population of each country. Results: Only 564 publications met our inclusion criteria. These articles came from 39 different countries, constituting 24% of all affected countries. China produced the greatest number of publications with 377 publications (67%). With respect to continental research activity, Asian countries had the highest research activity with 434 original publications (77%). In terms of publications per million persons (PPMPs), Singapore had the highest number of publications with 1.069 PPMPs. In terms of publications per billion-dollar GDP, Mauritius ranked first with 0.075. Conclusion: COVID-19 is a major disease that has impacted international public health on a global level. Observational studies and therapeutic trials pertaining to COVID-19 are essential for assessing pathogenic characteristics and developing novel treatment options.

negative: Seasonality of Coronavirus 229E, HKU1, NL63 and OC43 from 2014-2020 Abstract The possibility of seasonality of Covid-19 is being discussed; here we show clinical microbiology laboratory data illustrating seasonality of coronaviruses 229E, HKU1, NL63 and OC43. The data shown are specific to the four studied coronaviruses, and may or may not generalize to Covid-19.

negative: Comparison of risk factors for viral and nonviral asthma exacerbations

negative: Large-Scale Phylogenetic Analysis of Emerging Infectious Diseases Microorganisms that cause infectious diseases present critical issues of national security, public health, and economic welfare. For example, in recent years, highly pathogenic strains of avian influenza have emerged in Asia, spread through Eastern Europe, and threaten to become pandemic. As demonstrated by the coordinated response to Severe Acute Respiratory Syndrome (SARS) and influenza, agents of infectious disease are being addressed via large-scale genomic sequencing. The goal of genomic sequencing projects are to rapidly put large amounts of data in the public domain to accelerate research on disease surveillance, treatment, and prevention. However, our ability to derive information from large comparative genomic datasets lags far behind acquisition. Here we review the computational challenges of comparative genomic analyses, specifically sequence alignment and reconstruction of phylogenetic trees. We present novel analytical results on two important infectious diseases, Severe Acute Respiratory Syndrome (SARS) and influenza. SARS and influenza have similarities and important differences both as biological and comparative genomic analysis problems. Influenza viruses (Orthymxyoviridae) are RNA based. Current evidence indicates that influenza viruses originate in aquatic birds from wild populations. Influenza has been studied for decades via well-coordinated international efforts. These efforts center on surveillance via antibody characterization of the hemagglutinin (HA) and neuraminidase (N) proteins of the circulating strains to inform vaccine design. However, we still do not have a clear understanding of (1) various transmission pathways such as the role of intermediate hosts like swine and domestic birds and (2) the key mutation and genomic recombination events that underlie periodic pandemics of influenza. In the past 30 years, sequence data from HA and N loci has become an important data type. In the past year, full genomic data has become prominent. These data present exciting opportunities to address unanswered questions in influenza pandemics. SARS is caused by a previously unrecognized lineage of coronavirus, SARS-CoV, which like influenza has an RNA based genome. Although SARS-CoV is widely believed to have originated in animals, there remains disagreement over the candidate animal source that lead to the original outbreak of SARS. In contrast to the long history of the study of influenza, SARS was only recognized in late 2002 and the virus that causes SARS has been documented primarily by genomic sequencing. In the past, most studies of influenza were performed on a limited number of isolates and genes suited to a particular problem. Major goals in science today are to understand emerging diseases in broad geographic, environmental, societal, biological, and genomic contexts. Synthesizing diverse information brought together by various researchers is important to find out what can be done to prevent future outbreaks [JON03]. Thus comprehensive means to organize and analyze large amounts of diverse information are critical. For example, the relationships of isolates and patterns of genomic change observed in large datasets might not be consistent with hypotheses formed on partial data. Moreover when researchers rely on partial datasets, they restrict the range of possible discoveries. Phylogenetics is well suited to the complex task of understanding emerging infectious disease. Phylogenetic analyses can test many hypotheses by comparing diverse isolates collected from various hosts, environments, and points in time and organizing these data into various evolutionary scenarios. The products of a phylogenetic analysis are a graphical tree of ancestor–descendent relationships and an inferred summary of mutations, recombination events, host shifts, geographic, and temporal spread of the viruses. However, this synthesis comes at a price. The cost of computation of phylogenetic analysis expands combinatorially as the number of isolates considered increases. Thus, large datasets like those currently produced are commonly considered intractable. We address this problem with synergistic development of heuristics tree search strategies and parallel computing.

negative: A 28‐year study of human parainfluenza in Rio Grande do Sul, Southern Brazil PROBLEM: Human parainfluenza virus (hPIV) is an important pathogen in respiratory infections, however the health burden of hPIV is underestimated. This study describes the infections by hPIV1‐3 in Rio Grande do Sul, Brazil, from 1990 to 2017, providing data of the frequency and seasonality of cases and associated clinical symptoms. METHOD OF STUDY: Nasopharyngeal samples of patients with respiratory infection were collected, clinical data were analyzed, and immunofluorescence was used to detect hPIV. RESULTS: Respiratory viruses were detected in 33.63% of respiratory infections. In a total of 11 606 cases of viral respiratory infection, 781 were positive for hPIV; hPIV prevalence ranged from 2.14% to 27% of viral respiratory infections. hPIV1 circulates mainly during fall; hPIV3 circulation, in turn, starts in fall and peaks during spring; and cases of hPIV2 are reported along the year, with peaks in fall and early spring. The most affected age group was children, with hPIV prevalence of 74.23% in patients for less than 1 year. A higher proportion of girls were infected than boys, however, no difference by sex was observed considering all age groups. The most frequent type was hPIV3, especially in hospitalized patients. Both hPIV1 and 3 were associated with dyspnea, while hPIV2 caused mild symptoms mainly in nonhospitalized patients. Nineteen fatalities occurred, 89.5% of them associated with risk factors (prematurity; chronic diseases; age, <1 or >60 years). CONCLUSION: hPIV causes a high number of respiratory infections, leading to hospitalization especially in children; epidemiological and surveillance studies are important for the control and management of respiratory infections.

negative: Platelets to surrogate lung inflammation in COVID-19 Patients The neoteric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been jeopardizing the world with the symptoms of seasonal flu. The virus contagion predicted to have been originated from Wuhan, China has by far trapped 4,198,418 cases from 212 countries in the world with two international conveyances with 284,102 deaths as of 11 May 2020 (10:18 GMT). Researchers around the globe have indulged in deciphering viral mode in the body for devising a cure. Affirmations from autopsies and preliminary findings on SARS-CoV-2 hypothesized on viral pathogenesis within the host, for instance, source of inflammation in lungs and pneumonia. This hypothesis assigns the platelets as agents of infection after viral entry. Presently, curbing infection to stall the spread of SARS-CoV-2 is the prima facie intervention employed, worldwide. However, public health authorities must monitor the state of affairs scrupulously, as the deeper our understanding of this novel virus and its associated outbreak, the better we can deal with it. Knowing this idea might be far-fetched, yet this postulate would serve as the groundwork for the present situation.

negative: Information about the new coronavirus disease (COVID-19)

negative: The seasonal flight of influenza: a unified framework for spatiotemporal hypothesis testing Global mobility flow data are at the heart of spatial epidemiological models used to predict infectious disease behavior but this wealth of data on human mobility has been largely neglected by reconstructions of pathogen evolutionary dynamics using viral genetic data. Although stochastic models of viral evolution may potentially be informed by such data, a major challenge lies in deciding which mobility processes are critical and to what extent they contribute to shaping contemporaneous distributions of pathogen diversity. Here, we develop a framework to integrate predictors of viral diffusion with phylogeographic inference and estimate human influenza H3N2 migration history while simultaneously testing and quantifying the factors that underly it. We provide evidence for air travel governing the global dynamics of human influenza whereas other processes act at a more local scale.

negative: Is COVID-19 receiving ADE from other coronaviruses? Abstract One of the most perplexing questions regarding the current COVID-19 coronavirus epidemic is the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world. One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses. ADE modulates the immune response and can elicit sustained inflammation, lymphopenia, and/or cytokine storm, one or all of which have been documented in severe cases and deaths. ADE also requires prior exposure to similar antigenic epitopes, presumably circulating in local viruses, making it a possible explanation for the observed geographic limitation of severe cases and deaths.

negative: Human Genomic Loci Important in Common Infectious Diseases: Role of High-Throughput Sequencing and Genome-Wide Association Studies HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers.

negative: Diabetes and COVID-19: Global and Regional Perspectives Abstract The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.

negative: Relative frequency, Possible Risk Factors, Viral Codetection Rates, and Seasonality of Respiratory Syncytial Virus Among Children With Lower Respiratory Tract Infection in Northeastern Brazil Few studies, each limited to a single major city, have investigated the prevalence and seasonal patterns of different viruses among children with low respiratory tract infections (LRTI) in Northeastern Brazil. The aim of this study was to determine the frequency of respiratory syncytial virus (RSV) and of 7 other viruses in children for LRTI in 4 capitals from this region, and investigate their association with several risk factors, including meteorological data. From April 2012 to March 2013, 507 children, aged up to 24 months and hospitalized with LRTI in one of the participating centers at Aracajú, Salvador, Recife, and Maceió, had a sample of nasopharyngeal aspirate collected and analyzed for the following viruses by reverse-transcription polymerase chain reaction followed by hybridization on low-density microarrays: RSV, influenza, parainfluenza, adenovirus, rhinovirus, metapneumovirus, bocavirus, and coronavirus. The result was positive in 66.5% of cases, RSV was the most common virus (40.2%). Except for rhinovirus (17%), all other virus had frequency rates lower than 6%. Viral coinfections were detected in 13.8% of samples. Possible related risk factors for RSV infection were low age upon entry, attendance of daycare, low gestational age, and low educational level of the father. The relative frequency of viral infections was associated with increasing temperature and decreasing humidity separately, but the results also suggested both associated with increased frequency of RSV. Some of these findings differ from those reported for other regions in Brazil and may be used to guide policies that address LRTI.

negative: Influenza: Biology, Infection, and Control The growth of the human population has profoundly affected the global ecosystem, influencing the animal population balance, the availability of fresh water, arable land, biotic production, and atmospheric gases. The human ecological impact has significantly accelerated the evolutionary change of numerous organisms. For example, the production of human medicine and food has resulted in the rapid evolution of drug-resistant pathogenic organisms as well as plants and insects resistant to pesticides (Palumbi, 2001). Recently, the nutritional support of the human population has relied on the vast monoculture of domestic mammals and birds, which has facilitated the emergence of pathogenic enzootic organisms that infect both animals and humans. This chapter will focus on the global threat to human health represented by the highly contagious enzootic virus influenza. It will also discuss current efforts and future improvements to protect humans from global influenza epidemics and pandemics.

negative: Strategies supporting the prevention and control of neglected tropical diseases during and beyond the COVID-19 pandemic Emerging and re-emerging zoonotic diseases represent a public health challenge of international concern. They include a large group of neglected tropical diseases (NTDs), many of which are of zoonotic nature. Coronavirus disease 2019 (COVID-19), another emerging zoonotic disease, has just increased the stakes exponentially. Most NTDs are subject to the impact of some of the very same human-related activities triggering other emerging and re-emerging diseases, including COVID-19, severe acute respiratory syndrome (SARS), bird flu and swine flu. It is conceivable that COVID-19 will exacerbate the NTDs, as it will divert much needed financial and human resources. There is considerable concern that recent progress achieved with control and elimination efforts will be reverted. Future potential strategies will need to reconsider the determinants of health in NTDs in order to galvanize efforts and come up with a comprehensive, well defined programme that will set the stage for an effective multi-sectorial approach. In this Commentary, we propose areas of potential synergies between the COVID-19 pandemic control efforts, other health and non-health sector initiatives and NTD control and elimination programmes.

negative: How many are at increased risk of severe COVID-19 disease? Rapid global, regional and national estimates for 2020 Background The risk of severe COVID-19 disease is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 illness, and how this varies between countries may inform the design of possible strategies to shield those at highest risk. Methods We estimated the number of individuals at increased risk of severe COVID-19 disease by age (5-year age groups), sex and country (n=188) based on prevalence data from the Global Burden of Disease (GBD) study for 2017 and United Nations population estimates for 2020. We also calculated the number of individuals without an underlying condition that could be considered at-risk because of their age, using thresholds from 50-70 years. The list of underlying conditions relevant to COVID-19 disease was determined by mapping conditions listed in GBD to the guidelines published by WHO and public health agencies in the UK and US. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. Results We estimate that 1.7 (1.0 - 2.4) billion individuals (22% [15-28%] of the global population) are at increased risk of severe COVID-19 disease. The share of the population at increased risk ranges from 16% in Africa to 31% in Europe. Chronic kidney disease (CKD), cardiovascular disease (CVD), diabetes and chronic respiratory disease (CRD) were the most prevalent conditions in males and females aged 50+ years. African countries with a high prevalence of HIV/AIDS and Island countries with a high prevalence of diabetes, also had a high share of the population at increased risk. The prevalence of multimorbidity (>1 underlying conditions) was three times higher in Europe than in Africa (10% vs 3%). Conclusion Based on current guidelines and prevalence data from GBD, we estimate that one in five individuals worldwide has a condition that is on the list of those at increased risk of severe COVID-19 disease. However, for many of these individuals the underlying condition will be undiagnosed or not severe enough to be captured in health systems, and in some cases the increase in risk may be quite modest. There is an urgent need for robust analyses of the risks associated with different underlying conditions so that countries can identify the highest risk groups and develop targeted shielding policies to mitigate the effects of the COVID-19 pandemic.

negative: Coronavirus humains (HCoV) Résumé Les coronavirus forment un grand groupe de virus infectant les mammifères et les oiseaux ; cinq d’entre eux infectent l’homme : HCoV 229E et OC43, connus depuis les années 1960, SARS-CoV identifié en mars 2003 lors de l’épidémie de syndrome de détresse respiratoire aigu sévère, NL63 et HKU1, identifiés respectivement en 2004 et 2005. Ce sont des virus enveloppés dont le génome est une molécule d’ARN de polarité positive de très grande taille. Leur mode évolutif fait intervenir plusieurs paramètres : la génération de nombreux mutants lors de la réplication, responsable d’une distribution en quasi-espèces de la population virale, la capacité à établir des infections persistantes, la possibilité de délétions importantes, la grande flexibilité du génome due à un fort taux de recombinaisons homologues et hétérologues, la capacité à franchir les barrières d’espèces et à s’adapter au nouvel environnement. Les coronavirus (hors SARS-CoV) sont ubiquitaires et circulent sous forme épidémique. Les différents HCoV co-circulent avec une distribution entre les types qui est variable selon les années et les régions géographiques. Ce sont essentiellement des virus responsables d’infections respiratoires hautes et basses. Le SARS-CoV est, lui, un virus émergent responsable de l’épidémie de pneumopathies atypiques entre novembre 2002 et juillet 2003. Sa circulation a été interrompue grâce à la mise en place de mesures sanitaires drastiques. L’implication des HCoV dans des pathologies digestives et neurologiques reste à préciser. La détection des coronavirus est difficile, et fait appel surtout à des techniques moléculaires. Il n’existe actuellement aucun traitement spécifique des infections à HCoV. Abstract Coronaviruses are a large group of viruses and infect a lot of species of mammals and birds. Five coronaviruses currently infect humans: HCoVs 229E and OC43, identified in the 1960s, SARS-CoV identified in March 2003 during the SARS epidemic, and the HCoVs NL63 and HKU1, identified in 2004 and 2005 respectively. The genome of the coronaviruses is a linear, non-segmented, positive-sense single-stranded RNA molecule of approximately 30kb. The evolution of these viruses occurs through some features: the generation of multiple mutants during the replication resulting on a quasispecies structure of the viral population, the demonstrated ability of coronaviruses to establish persistent infections, the flexibility of the genome due to a high frequency of homologue or heterologue recombinations, the ability to jump barrier species and to adapt to the new environment. Two epidemiologic pictures of HCoV infections have to be distinguished: as suggested by recent studies, HCoVs except SARS-CoV, are distributed worldwide and cocirculate during seasonal outbreaks. The distribution of the different HCoV species varies according to the geographic area and season. In contrast, the SARS-CoV is responsible of the first emerging infectious disease of this millennium, infecting more than 8000 people between November 2002 and July 2003. Its circulation has been stopped by drastic public health policy. Human coronaviruses may be also involved in enteric and neurologic diseases. The detection of these viruses is difficult and mainly based on molecular assays (RT-PCR). There is no established specific therapy to date.

negative: Genetic distance of SARS coronavirus from the recent natural case Abstract Phylogenetic analysis of SARS coronavirus isolates based on the spike gene and protein sequence using Neighbor-Joining, maximum likelihood and Bayesian inference methods indicated that a recent human SARS-CoV isolate was closer to some human SARS-CoV isolates from earlier epidemic phase than to the SARS-CoV-like viruses isolated from wild animals during previous epidemic phase. A reasonable judgment based on phylogenetic relationship and sequence variations it is likely that the recent human SARS-CoV isolate is closer to an unknown SARS-CoV predecessor.

negative: Retrospective analysis of the possibility of predicting the COVID-19 outbreak from Internet searches and social media data, China, 2020 The peak of Internet searches and social media data about the coronavirus disease 2019 (COVID-19) outbreak occurred 10–14 days earlier than the peak of daily incidences in China. Internet searches and social media data had high correlation with daily incidences, with the maximum r > 0.89 in all correlations. The lag correlations also showed a maximum correlation at 8–12 days for laboratory-confirmed cases and 6–8 days for suspected cases.

negative: Estimating required 'lockdown' cycles before immunity to SARS-CoV-2: Model-based analyses of susceptible population sizes, 'S0', in seven European countries including the UK and Ireland We used Bayesian model inversion to estimate epidemic parameters from the reported case and death rates from seven countries using data from late January 2020 to April 5th 2020. Two distinct generative model types were employed: first a continuous time dynamical-systems implementation of a Susceptible-Exposed-Infectious-Recovered (SEIR) model and second: a partially observable Markov Decision Process (MDP) or hidden Markov model (HMM) implementation of an SEIR model. Both models parameterise the size of the initial susceptible population (S0), as well as epidemic parameters. Parameter estimation (data fitting) was performed using a standard Bayesian scheme (variational Laplace) designed to allow for latent unobservable states and uncertainty in model parameters. Both models recapitulated the dynamics of transmissions and disease as given by case and death rates. The peaks of the current waves were predicted to be in the past for four countries (Italy, Spain, Germany and Switzerland) and to emerge in 0.5-2 weeks in Ireland and 1-3 weeks in the UK. For France one model estimated the peak within the past week and the other in the future in two weeks. Crucially, Maximum a posteriori (MAP) estimates of S0 for each country indicated effective population sizes of below 20% (of total population size), under both the continuous time and HMM models. With a Bayesian weighted average across all seven countries and both models, we estimated that 6.4% of the total population would be immune. From the two models the maximum percentage of the effective population was estimated at 19.6% of the total population for the UK, 16.7% for Ireland, 11.4% for Italy, 12.8% for Spain, 18.8% for France, 4.7% for Germany and 12.9% for Switzerland. Our results indicate that after the current wave, a large proportion of the total population will remain without immunity.

negative: Viral pathogens among elderly people with acute respiratory infections in Shanghai, China: Preliminary results from a laboratory‐based surveillance, 2012‐2015 Acute respiratory infections (ARIs), with viral pathogens as the major contributors, are the most common illnesses worldwide, and increase the morbidity and mortality among the elderly population. The clinical and pathological features of elderly people with ARIs need to be identified for disease intervention. From January 1, 2012 through December 31, 2015, respiratory specimens from patients above 60 years old with ARIs were collected from the outpatient and inpatient settings of six sentinel hospitals in Pudong New Area. Each specimen was tested via multiplex polymerase chain reaction (PCR) for eight target viral etiologies including influenza, human rhinovirus (HRV), human para‐influenza virus (PIV), adenovirus (ADV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human coronavirus (hCoVs), and human bocavirus (hBoV). A total of 967 elderly patients with ARIs were enrolled, including 589 (60.91%) males, and the median age was 73 years old. 306 (31.64%) patients were tested positive for any one of the eight viruses, including 276 single infections and 30 co‐infections. Influenza was the predominant virus (14.17%, 137/967), detected from 21.35% (76/356) of the outpatients and 9.98% (61/611) of the inpatients. Influenza infections presented two annual seasonal peaks during winter and summer. Compared with non‐influenza patients, those with influenza were more likely to have fever, cough, sore throat, and fatigue. This study identified influenza as the leading viral pathogen among elderly with ARIs, and two seasonal epidemic peaks were observed in Shanghai. An influenza vaccination strategy needs to be advocated for the elderly population.

negative: SARS Coronavirus Replicative Enzymes: Structures and Mechanisms The SARS coronavirus (SARS-CoV) replicase gene encodes 16 nonstructural proteins (nsps) with multiple enzymatic activities. Several of these enzymes are common components of replication complexes of other plus-strand RNA viruses, such as picornavirus 3C-like protease, papain-like protease, RNA-dependent RNA polymerase, RNA helicase, and ribose 2′-O-methyltransferase activities, while others such as exoribonuclease, endoribonuclease, and adenosine diphosphate-ribose 1″-phosphatase activities, are rarely or not conserved in viruses outside the order Nidovirales. The latter enzymes are believed to be involved in unique metabolic pathways used by coronaviruses to (1) replicate and transcribe their extremely large RNA genomes, and (2) interfere with cellular functions and antiviral host responses. Since the global outbreak of SARS in 2003, major efforts have been made to elucidate the structures of the protein components of the SARS-CoV replication/transcription complex. Thus, in less than 5 years, the structures of as many as 16 SARS-CoV proteins or functional domains have been determined. Remarkably, eight of these 16 structures had novel folds, illustrating the uniqueness of the coronavirus replicative machinery. Furthermore, several new protein functions and potential drug targets have been identified in these studies. Current structural studies mainly focus on the few remaining proteins for which no structural information is available and larger protein complexes comprised of different nsps. The studies aim at obtaining detailed information on the functions and macromolecular assembly of the coronavirus replication/transcription machinery which, over a long period of time, may be used to develop selective antiviral drugs. This chapter reviews structural information on the SARS-CoV macro domain (ADRP) as well as nsps 7, 8, 9, and 15 and summarizes our current knowledge of active-site residues and intermolecular interactions of these proteins.

negative: Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2 The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne® was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.

negative: Severe pneumonia among Kenyan infants and children.

negative: Knowledge and Perceptions of COVID-19 Among Health Care Workers: Cross-Sectional Study BACKGROUND: During the first week of March, the coronavirus disease 2019 (COVID-19) outbreak reached more than 100 countries with over 100,000 cases. Health care authorities have already initiated awareness and preparedness activities worldwide. A poor understanding of the disease among health care workers (HCWs) may result in delayed treatment and result in the rapid spread of the infection. OBJECTIVE: This study aimed to investigate the knowledge and perceptions of HCWs about COVID-19. METHODS: A cross-sectional, web-based study was conducted among HCWs about COVID-19 during the first week of March 2020. A 23-item survey instrument was developed and distributed randomly to HCWs using social media; it required 5 minutes to complete. A chi-square test was used to investigate the level of association among variables, with significance set to P<.05. RESULTS: Of 529 participants, a total of 453 HCWs completed the survey (response rate: 85.6%); 51.6% (n=234) were male, 32.1% (n=147) were aged 25-34 years, and most were doctors (n=137, 30.2%) and medical students (n=134, 29.6%). Most participants (n=276, 61.0%) used social media to obtain information on COVID-19. A significant proportion of HCWs had poor knowledge of its transmission (n=276, 61.0%) and symptom onset (n=288, 63.6%) and showed positive perceptions of COVID-19. Factors such as age and profession were associated with inadequate knowledge and a poor perception of COVID-19. CONCLUSIONS: As the global threat of COVID-19 continues to emerge, it is critical to improve the knowledge and perceptions of HCWs. Educational interventions are urgently needed to reach HCWs worldwide, and further studies are warranted.

negative: Covid-19: Impact on Perianesthesia Nursing Areas

negative: A systematic review of studies on forecasting the dynamics of influenza outbreaks Forecasting the dynamics of influenza outbreaks could be useful for decision-making regarding the allocation of public health resources. Reliable forecasts could also aid in the selection and implementation of interventions to reduce morbidity and mortality due to influenza illness. This paper reviews methods for influenza forecasting proposed during previous influenza outbreaks and those evaluated in hindsight. We discuss the various approaches, in addition to the variability in measures of accuracy and precision of predicted measures. PubMed and Google Scholar searches for articles on influenza forecasting retrieved sixteen studies that matched the study criteria. We focused on studies that aimed at forecasting influenza outbreaks at the local, regional, national, or global level. The selected studies spanned a wide range of regions including USA, Sweden, Hong Kong, Japan, Singapore, United Kingdom, Canada, France, and Cuba. The methods were also applied to forecast a single measure or multiple measures. Typical measures predicted included peak timing, peak height, daily/weekly case counts, and outbreak magnitude. Due to differences in measures used to assess accuracy, a single estimate of predictive error for each of the measures was difficult to obtain. However, collectively, the results suggest that these diverse approaches to influenza forecasting are capable of capturing specific outbreak measures with some degree of accuracy given reliable data and correct disease assumptions. Nonetheless, several of these approaches need to be evaluated and their performance quantified in real-time predictions.

negative: Relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses BACKGROUND: A(H1N1)pdm09, a new influenza pandemic virus emerged in 2009. The A(H1N1)pdm09 infection had several unique characteristics which included rapid transmissibility and high morbidity in obese individuals, pregnant women and individuals suffering from chronic diseases. OBJECTIVES: To study the relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses such as respiratory syncytial virus (RSV), human metapneumo virus (hMPV), adenovirus and seasonal influenza. METHODS: Samples (nasopharyngeal swabs or aspirates) collected between 2007 until 2012 from patients of various ages that were hospitalized due to respiratory virus infections were analyzed for the presence of various respiratory viruses, using qRT‐PCR. RESULTS: In 2009–2010, when the pandemic influenza A(H1N1)pdm09 first appeared, two major infection peaks were noted and individuals of various ages were infected. Following the decline of the A(H1N1)pdm09 virus infection, the percentages of patients infected with adenovirus and hMPV increased, while infection frequency with RSV B and with seasonal influenza virus decreased. Furthermore, RSV infections were delayed and very few percentages of patients were co‐infected with more than one virus. Interestingly, the A(H1N1)pdm09 virus lost its dominancy when it reappeared in the winter of 2010–2011, and at this time, only the incidence of RSV infections was affected by the A(H1N1)pdm09 virus. CONCLUSIONS: The A(H1N1)pdm09 virus had distinct effects on other respiratory viruses when it first appeared versus later, when it evolved from being a pandemic to a seasonal virus.

negative: Viral pathogens of acute lower respiratory tract infection in China. OBJECTIVES To document the viral etiology of acute lower respiratory tract infection (ALRIs) in Chinese children. SETTING Children Hospital, Zhejiang University, China. STUDY DESIGN Cross-sectional. PARTICIPANTS 34885 children with ALRI between January 2001 to December 2006. METHODS Nasopharyngeal aspirates were collected from all subjects. Respiratory syncytial virus (RSV), adenovirus (ADV), type 1 to 3 parainfluenza viruses (PIV), and type A and B influenza virus (Flu) were detected by direct immunofluorescence. RESULTS Viruses were identified in 32.3% cases, including RSV (23.6%), PIV 3 (4.3%), Flu A (2.0%), ADV (1.7%), PIV I (0.6%), Flu B (0.2%) and PIV 2 (0.1%). RSV and PIV 3 predominated in younger children while Flu A and Flu B predominated in older children (P<0.001, respectively). PIV 1 was more prevalent in children aged 1 to 3 years. The peak frequency of RSV, PIV 3 and Flu A were in early spring, June to August, and August and September, respectively. Flu B had a peak in the winter and spring. Adenovirus infections occurred in all seasons with a relatively constant frequency. CONCLUSIONS Viruses are an important cause of ALRIs in Chinese children constituting 1/3 of total cases. RSV is the most common pathogen.

negative: Online Social Networks Flu Trend Tracker: A Novel Sensory Approach to Predict Flu Trends Seasonal influenza epidemics cause several million cases of illnesses cases and about 250,000 to 500,000 deaths worldwide each year. Other pandemics like the 1918 “Spanish Flu” may change into devastating event. Reducing the impact of these threats is of paramount importance for health authorities, and studies have shown that effective interventions can be taken to contain the epidemics, if early detection can be made. In this paper, we introduce Social Network Enabled Flu Trends (SNEFT), a continuous data collection framework which monitors flu related messages on online social networks such as Twitter and Facebook and track the emergence and spread of an influenza. We show that text mining significantly enhances the correlation between online social network(OSN) data and the Influenza like Illness (ILI) rates provided by Centers for Disease Control and Prevention (CDC). For accurate prediction, we implemented an auto-regression with exogenous input (ARX) model which uses current OSN data and CDC ILI rates from previous weeks to predict current influenza statistics. Our results show that, while previous ILI data from the CDC offer a true (but delayed) assessment of a flu epidemic, OSN data provides a real-time assessment of the current epidemic condition and can be used to compensate for the lack of current ILI data. We observe that the OSN data is highly correlated with the ILI rates across different regions within USA and can be used to effectively improve the accuracy of our prediction. Therefore, OSN data can act as supplementary indicator to gauge influenza within a population and helps to discover flu trends ahead of CDC.

negative: Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection Summary Background The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis of various isolates might provide an indication of potential strain differences of this new virus. Moreover, mutation analysis will help to develop effective vaccines. Methods We sequenced the entire SARS viral genome of cultured isolates from the index case (SIN2500) presenting in Singapore, from three primary contacts (SIN2774, SIN2748, and SIN2677), and one secondary contact (SIN2679). These sequences were compared with the isolates from Canada (TOR2), Hong Kong (CUHK-W1 and HKU39849), Hanoi (URBANI), Guangzhou (GZ01), and Beijing (BJ01, BJ02, BJ03, BJ04). Findings We identified 129 sequence variations among the 14 isolates, with 16 recurrent variant sequences. Common variant sequences at four loci define two distinct genotypes of the SARS virus. One genotype was linked with infections originating in Hotel M in Hong Kong, the second contained isolates from Hong Kong, Guangzhou, and Beijing with no association with Hotel M (p<0.0001). Moreover, other common sequence variants further distinguished the geographical origins of the isolates, especially between Singapore and Beijing. Interpretation Despite the recent onset of the SARS epidemic, genetic signatures are emerging that partition the worldwide SARS viral isolates into groups on the basis of contact source history and geography. These signatures can be used to trace sources of infection. In addition, a common variant associated with a non-conservative aminoacid change in the S1 region of the spike protein, suggests that immunological pressures might be starting to influence the evolution of the SARS virus in human populations. Published online May 9, 2003 http://image.thelancet.com/extras/03art4454web.pdf

negative: The origin of acute respiratory epidemics After studying the dependence of acute respiratory diseases of all etiologies on air temperature and population immunity dynamics, the authors proposed that the air temperature and the immunity level can affect disease resistance. Knowledge of the relationship between these factors must clarify the mechanisms that determine morbidity dynamics.

negative: Is a 14-day quarantine period optimal for effectively controlling coronavirus disease 2019 (COVID-19)? Background The outbreak of a new coronavirus (SARS-CoV-2) disease (Covid-19) has become pandemic. To be more effectively controlling the disease, it is critical to set up an optimal quarantine period so that about 95% of the cases developing symptoms will be retained for isolation. At the moment, the WHO-established quarantine period is 14 days based on previous reports which had studied small sizes of hospitalized cases (10 and ~100, respectively), however, over 80% of adult- and 95% of child-cases were not necessary to stay in hospitals, and therefore, had not been hospitalized. Therefore, we are questioning if the current-inferred median incubation time is representative for the whole Covid-19 population, and if the current quarantine period is optimal. Methods We compiled and analyzed the patient-level information of 2015 laboratory-confirmed Covid-19 cases including 99 children in 28 Chinese provinces. This cohort represents a wide-range spectrum of Covid-19 disease with both hospitalized and non-hospitalized cases. Results The full range of incubation periods of the Covid-19 cases ranged from 0 to 33 days among 2015 cases. There were 6 (0.13%) symptom-free cases including 4 females with a median age of 25.5 years and 2 males with a median age of 36 years. The median incubation period of both male and female adults was similar (7-day) but significantly shorter than that (9-day) of child cases (P=0.02). This cohort contained 4 transmission generations, and incubation periods of the cases between generations were not significantly different, suggesting that the virus has not been rapidly adapted to human beings. Interestingly, incubation periods of 233 cases (11.6%) were longer than the WHO-established quarantine period (14 days). Data modeling suggested that if adults take an extra 4-day or 7-day of isolation (i.e., a quarantine period of 18 or 21 days), 96.2% or 98.3%, respectively, of the people who are developing symptoms will be more effectively quarantined. Patients transmitted via lunch/dinner parties (i.e., gastrointestinal tract infection through oral transmission) had a significantly longer incubation period (9-day) than other adults transmitted via respiratory droplets or contaminated surfaces and objects (P<0.004). Conclusions The whole Covid-19 population including both hospitalized and non-hospitalized cases had a median incubation period of 7-day for adults, which is 1.8-day longer than the hospitalized cases reported previously. An extension of the adult quarantine period to 18 days or 21 days could be more effective in preventing virus-spreading and controlling the disease. The cases transmitted by lunch/dinner parties could be infected first in the gastrointestinal tract through oral transmission and then infected in the respiratory system so that they had a longer incubation period.

negative: Mortality of the COVID-19 outbreak in Sweden in relation to previous severe disease outbreaks Influenza viruses have caused disease outbreaks in human societies for a long time. Influenza often has rapid onset and relatively short duration, both in the individual and in the population. The case fatality rate varies for different strains of the virus, as do the effects on total mortality. Outbreaks related to coronavirus infections have recently become a global concern but much less is known about the dynamics of these outbreaks and their effects on mortality. In this work, disease outbreaks in Sweden, in the time period of 1860-2020, are characterized and compared to the currently ongoing COVID-19 outbreak. The focus is on outbreaks with a sharp increase in all-cause mortality. Outbreak onset is defined as the time point when deaths counts starts to increase consistently for a period of 10 days. The duration of the outbreak is defined as the time period in which mortality rates are elevated. Excess mortality is estimated by standard methods. In total there were 15 outbreaks detected in the time period, the first 14 were likely caused by influenza virus infections, the last by SARS-CoV-2. The mortality dynamics of the SARS-CoV-2 outbreak is shown to be similar to outbreaks due to influenza virus, and in terms of the number of excess deaths, might become the worst outbreak since the 'Spanish flu' of 1918-1919.

negative: Genomics of Emerging Infectious Disease: A PLoS Collection

negative: Policies on the use of respiratory protection for hospital health workers to protect from coronavirus disease (COVID-19)

negative: Antiviral activity of Isatidis Radix derived glucosinolate isomers and their breakdown products against influenza A in vitro/ovo and mechanism of action Abstract Ethnopharmacological relevance Isatidis Radix, the sun-dried roots of Isatis indigotica Fortune ex Lindl., is one of the most usually used traditional Chinese medicines. For centuries, the herb has been employed in clinical practice for treatment of virus infection and inflammation. However, its active ingredients remain unclear. Aim of the study In the present study, the anti-influenza virus activity of epiprogoitrin, progoitrin, epigoitrin and goitrin, the Isatidis Radix derived glucosinolate isomers and their breakdown products, was firstly evaluated in vitro and in ovo and their mechanism of action was investigated. Materials and methods Epiprogoitrin, progoitrin, epigoitrin and goitrin were isolated from Isatidis Radix by chiral separation. In vitro and in ovo evaluations were performed on Madin-Darby canine kidney (MDCK) cells and embryonated eggs respectively, both using protocols including prevention, treatment and virus neutralization. Hemagglutination (HA) and neuraminidase (NA) inhibition assays were performed for further understanding of the antiviral mechanism. Results Isatidis Radix derived glucosinolate isomers and their breakdown products all exhibited dose-dependent inhibition effect against influenza A virus (H1N1) without toxicity. The antiviral potency of the components was in the order of progoitrin > goitrin > epigoitrin > epiprogoitrin. The attachment of the constituents to the viral envelope conduced to the mechanism of their antiviral action without disturbing viral adsorption or budding. Conclusion Taken together, these results are promising for further development of Isatidis Radix and may contribute an adjunct to pharmacotherapy for influenza virus infection.

negative: Respiratory Viral Infections in Chronic Lung Diseases Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis (CF) and interstitial lung diseases (ILD), affect many individuals worldwide. Patients with these chronic lung diseases are susceptible to respiratory lung infections and some of these viral infections can contribute to disease pathogenesis. This review highlights the associations of lung infections and the respective chronic lung diseases and how infection in the different lung diseases affects disease exacerbation and progression.

negative: Azithromycin and COVID‐19Prompt Early Use at First Signs of this Infection in Adults and Children An Approach Worthy of Consideration The devastating effects of the coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2) has led to urgent attempts to find effective therapeutic agents for inpatient and outpatient treatment of COVID‐19. Initial enthusiasm for the combination of hydroxychloroquine and azithromycin has abated. However, as a result of positive clinical experience with azithromycin used alone during the first few days of the flu‐like illness caused by this coronavirus, we recommend formal clinical trials using azithromycin early in the course of a COVID‐19 infection. There is one clinical trial initiated, the individually‐randomized, telemedicine‐based, “Azithromycin for COVID‐19 Treatment in Outpatients Nationwide (ACTION)” based at the University of California San Francisco. This placebo‐controlled trial is designed to determine the efficacy of a single 1.2 g dose of oral azithromycin to prevent COVID‐19 patient progression to hospitalization. We recommend formal clinical trials of azithromycin in its prepackaged form at the first sign of COVID‐19 infection in adults and children, using an initial adult dose of 500 mg followed by 250 mg per day for four days, a total cumulative dose of 1.5 g, and for children 5 to 18 years of age, 10 mg/kg on the first day followed by 5 mg/kg for four days. This article is protected by copyright. All rights reserved.

negative: Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection? We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing “trained” nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a “low-risk–high-reward” preventive measure in saving lives during this unprecedented COVID-19 pandemic.

negative: Association Between US Administration Endorsement of Hydroxychloroquine for COVID-19 and Outpatient Prescribing

negative: Confronting an influenza pandemic: ethical and scientific issues. The prolonged concern over the potential for a global influenza pandemic to cause perhaps many millions of fatalities is a chilling one. After the SARS (severe acute respiratory syndrome) scares [1], attention has turned towards the possibility of an avian influenza virus hybridizing with a human influenza virus to create a highly virulent, as yet unknown, killer, on a scale unseen since the Spanish flu outbreak of 1918, which produced more fatalities than the Great War. In deciding how countries should react to this potential pandemic, individually and collectively, a reasonable and practical balance must be struck between the rights and obligations of individual citizens and protection of the wider community and, indeed, society as a whole. In this communication, ethical issues are discussed in the context of some of the scientific questions relating to a potential influenza pandemic. Among these issues are the rights and obligations of healthcare professionals, difficulties surrounding resource allocation, policies that have an impact on liberty and trade, when and how to introduce any vaccine or other form of mass treatment, global governance questions and the role of health policies in contemporary society. By considering these issues and questions in advance of an influenza, or indeed any other, pandemic commencing, countries can be better prepared to deal with the inevitably difficult decisions required during such events, rather than dusting down outdated previous plans, or making and implementing policy in an ad hoc manner with a resultant higher risk of adverse consequences.

negative: ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as "bridge regions" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.

negative: Preliminary evidence that higher temperatures are associated with lower incidence of COVID-19, for cases reported globally up to 29th February 2020 Seasonal variation in COVID-19 incidence could impact the trajectory of the pandemic. Using global line-list data on COVID-19 cases reported until 29th February 2020 and global gridded temperature data, and after adjusting for surveillance capacity and time since first imported case, higher average temperature was strongly associated with lower COVID-19 incidence for temperatures of 1°C and higher. However, temperature explained a relatively modest amount of the total variation in COVID-19 incidence. These preliminary findings support stringent containment efforts in Europe and elsewhere.

negative: Influenza and COVID-19 Co-infection: Report of 6 cases and review of the Literature. COVID-19 pandemic caused infection in a season when influenza is still prevalent. Both viruses have similar transmission characteristics and common clinical manifestations. Influenza has been described to cause respiratory infection with some other respiratory pathogens. However the information of COVID-19 and influenza co-infection is limited. In this study, we reported our co-infected cases and reviewed the literature. We included all COVID-19 diagnosed patients. All patients with a presumed diagnosis of COVID-19 were routinely screened for influenza. Their thorax radiology was reviewed for COVID-19 -influenza differentiation. During the study period, 1103 patients have been diagnosed COVID-19. Among them, 6 patients (0.54%) were diagnosed co-infected with influenza. There have been 28 more co-infected patients reported. Laboratory-based, screening studies reported more patients. Thorax radiology findings were compatible with COVID-19 in 5 and with influenza in 1 one of our patients. Our cases were mild-to-moderate in severity. The reported cases in the literature included patients died (n=2) and those living ventilator dependent or under mechanical ventilation. COVID-19 and influenza co-infection is rare. Screening studies report more cases, suggesting that unless screening COVID-19 patients, the co-infection remains undiagnosed and underestimated. Increasing experience in thoracic radiology may contribute to diagnose the responsible virus(es) from the clinical illness. Influenza vaccine for larger population groups can be recommended to simplify clinicians' work. This article is protected by copyright. All rights reserved.

negative: Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission Background: Influenza virus presents a significant challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid diagnosis of infection, rationalising antimicrobial therapy, and supporting interventions for infection control. This study aimed to evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings. Methods: We conducted Nanopore metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic testing. We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data. Results: Metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses compared with the diagnostic standard (Cepheid Xpress/BioFire FilmArray Respiratory Panel). We identified a H3N2 genome with the oseltamivir resistant S331R mutation in the NA protein, potentially associated with the emergence of a distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in the infectious diseases ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant strain circulating in the community. We also detected a range of other potentially pathogenic viruses and bacteria from the metagenome. Conclusion: Nanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Generation of full genomes can contribute to the investigation and management of nosocomial outbreaks.

negative: COVID-19: the First Documented Coronavirus Pandemic in History Abstract The novel human coronavirus disease COVID-19 has become the fifth documented pandemic since the 1918 flu pandemic. COVID-19 was first reported in Wuhan, China, and subsequently spread worldwide. The coronavirus was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses based on phylogenetic analysis. SARS-CoV-2 is believed to be a spillover of an animal coronavirus and later adapted the ability of human-to-human transmission. Because the virus is highly contagious, it rapidly spreads and continuously evolves in the human population. In this review article, we discuss the basic properties, potential origin, and evolution of the novel human coronavirus. These factors may be critical for studies of pathogenicity, antiviral designs, and vaccine development against the virus.

negative: Respiratory Tract Viral Infections and Coinfections Identified by Anyplex™ II RV16 Detection Kit in Pediatric Patients at a Riyadh Tertiary Care Hospital Respiratory infections are caused by an array of viruses, and limited information is available about viral coexistence, comparative symptoms, and the burden of illness. This retrospective cohort study aimed to determine the etiological agents responsible for respiratory tract infections by Anyplex II RV16 detection kit (RV16, Seegene), involving 2266 pediatric patients with respiratory infections admitted to the Department of Pediatrics at King Abdul-Aziz Medical City, Ministry of National Guard, Riyadh, from July 2014 to June 2015. The most frequent respiratory infections were recorded in the 1 to 5 year age group (44.7%). Rhinovirus (32.5%), Adenovirus (16.9%), and Respiratory syncytial virus (RSV) B (10.4%) were most common. In single viral infections, Rhinovirus (41.2%), Metapneumovirus (15.3%), and Bocavirus (13.7%) were most frequent. In multiple viral infections, Rhinovirus (36.7%), Adenovirus (35.2%), Bocavirus (11.2), RSV B (7.8%), and RSV A (6.7%) were most frequent. No significant difference was observed in clinical presentations; however, rhinorrhea and hypodynamia were significantly associated with viral respiratory infections. Most respiratory viral pathogens peaked during December, January, March, and April. Rhinovirus, Adenovirus, and Bocavirus circulations were detected throughout the year. Winter peaks were recorded for Rhinovirus, RSV B, Adenovirus, and RSV A, whereas the Metapneumovirus, and the Bocavirus peaked in March and April. These findings enhance understanding of viral etiology and distribution to improve respiratory infection management and treatment.

negative: Inference and forecast of H7N9 influenza in China, 2013 to 2015 The recent emergence of A(H7N9) avian influenza poses a significant challenge to public health in China and around the world; however, understanding of the transmission dynamics and progression of influenza A(H7N9) infection in domestic poultry, as well as spillover transmission to humans, remains limited. Here, we develop a mathematical model–Bayesian inference system which combines a simple epidemic model and data assimilation method, and use it in conjunction with data on observed human influenza A(H7N9) cases from 19 February 2013 to 19 September 2015 to estimate key epidemiological parameters and to forecast infection in both poultry and humans. Our findings indicate a high outbreak attack rate of 33% among poultry but a low rate of chicken-to-human spillover transmission. In addition, we generated accurate forecasts of the peak timing and magnitude of human influenza A(H7N9) cases. This work demonstrates that transmission dynamics within an avian reservoir can be estimated and that real-time forecast of spillover avian influenza in humans is possible.

negative: Detection methods for influenza A H1N1 virus with special reference to biosensors: a review H1N1 (Swine flu) is caused by influenza A virus, which is a member of Orthomyxoviridae family. Transmission of H1N1 occurs from human to human through air or sometimes from pigs to humans. The influenza virus has different RNA segments, which can reassert to make new virus strain with the possibility to create an outbreak in unimmunized people. Gene reassortment is a process through which new strains are emerging in pigs, as it has specific receptors for both human influenza and avian influenza viruses. H1N1 binds specifically with an α-2,6 glycosidic bond, which is present in human respiratory tract cells as well as in pigs. Considering the fact of fast multiplication of viruses inside the living cells, rapid detection methods need an hour. Currently, WHO recommended methods for the detection of swine flu include real-time PCR in specific testing centres that take 3–4 h. More recently, a number of methods such as Antigen–Antibody or RT-LAMP and DNA biosensors have also been developed that are rapid and more sensitive. This review describes the various challenges in the diagnosis of H1N1, and merits and demerits of conventional vis-à-vis latest methods with special emphasis on biosensors.

negative: Passive Broad-Spectrum Influenza Immunoprophylaxis Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics. Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals. However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance. The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest. Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks. Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic. Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.

negative: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.

negative: Acute respiratory tract infections in elderly patients increase systemic levels of hemostatic proteins

negative: Possible interference between seasonal epidemics of influenza and other respiratory viruses in Hong Kong, 2014–2017 BACKGROUND: Unlike influenza viruses, little is known about the prevalence and seasonality of other respiratory viruses because laboratory surveillance for non-influenza respiratory viruses is not well developed or supported in China and other resource-limited countries. We studied the interference between seasonal epidemics of influenza viruses and five other common viruses that cause respiratory illnesses in Hong Kong from 2014 to 2017. METHODS: The weekly laboratory-confirmed positive rates of each virus were analyzed from 2014 to 2017 in Hong Kong to describe the epidemiological trends and interference between influenza viruses, respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus, enterovirus and rhinovirus. A sinusoidal model was established to estimate the peak timing of each virus by phase angle parameters. RESULTS: Seasonal features of the influenza viruses, PIV, enterovirus and adenovirus were obvious, whereas annual peaks of RSV and rhinovirus were not observed. The incidence of the influenza viruses usually peaked in February and July, and the summer peaks in July were generally caused by the H3 subtype of influenza A alone. When influenza viruses were active, other viruses tended to have a low level of activity. The peaks of the influenza viruses were not synchronized. An epidemic of rhinovirus tended to shift the subsequent epidemics of the other viruses. CONCLUSION: The evidence from recent surveillance data in Hong Kong suggests that viral interference during the epidemics of influenza viruses and other common respiratory viruses might affect the timing and duration of subsequent epidemics of a certain or several viruses.

negative: CoAID: COVID-19 Healthcare Misinformation Dataset As the COVID-19 virus quickly spreads around the world, unfortunately, misinformation related to COVID-19 also gets created and spreads like wild fire. Such misinformation has caused confusion among people, disruptions in society, and even deadly consequences in health problems. To be able to understand, detect, and mitigate such COVID-19 misinformation, therefore, has not only deep intellectual values but also huge societal impacts. To help researchers combat COVID-19 health misinformation, therefore, we present CoAID (Covid-19 heAlthcare mIsinformation Dataset), with diverse COVID-19 healthcare misinformation, including fake news on websites and social platforms, along with users' social engagement about such news. CoAID includes 1,896 news, 183,564 related user engagements, 516 social platform posts about COVID-19, and ground truth labels. The dataset is available at: https://github.com/cuilimeng/CoAID.

negative: Chapter 19 Orthomyxoviruses of Fish Abstract The family Orthomyxoviridae is well known for containing influenza viruses with a segmented RNA genome that is prone to gene reassortment in mixed infections (known as antigenic shift) resulting in new virus subtypes that cause pandemics, and cumulative mutations (known as antigenic drift), resulting in new virus strains that cause epidemics. This family also contains infectious salmon anemia virus (ISAV) and tilapia lake virus (TiLV), which are a unique orthomyxoviruses that infect fish and is unable to replicate above room temperature (24°C). This chapter describes the comparative virology of members in the family Orthomyxoviridae in general, helping to understand the emergent teleost orthomyxoviruses, ISAV and TiLV. The most current information on virus–host interactions of the fish orthomyxoviruses, particularly ISAV, as they relate to variations in virus structure, virulence, persistence, host range and immunological aspects is presented in detail.

negative: COVID-19 pandemic: examining the faces of spatial differences in the morbidity and mortality in sub-Saharan Africa, Europe and USA. Background: COVID-19, the disease associated with the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently a global pandemic with several thousands of confirmed cases of infection and death. However, the death rate across affected countries shows variation deserving of critical evaluation. Methods: In this study, we evaluated differentials in COVID-19 confirmed cases of infection and associated deaths of selected countries in Sub-Sahara Africa (Nigeria and Ghana), South Africa, Europe (Italy, Spain, Sweden and UK) and USA. Data acquired for various standard databases on mutational shift of the SARS-CoV-2 virus based on geographical location, BCG vaccination policy, malaria endemicity, climatic conditions (temperature), differential healthcare approaches were evaluated over a period of 45 days from the date of reporting the index case. Results: The number of confirmed cases of infection and associated deaths in Sub-Sahara Africa were found to be very low compared to the very high values in Europe and USA over the same period. Recovery rate from COVID-19 is not correlated with the mutational attributes of the virus with the sequenced strain from Nigeria having no significant difference (p>0.05) from other geographical regions. Significantly higher (p<0.05) infection rate and mortality from COVID-19 were observed in countries (Europe and USA) without a current universal BCG vaccination policy compared to those with one (Sub-Sahara African countries). Countries with high malaria burden had significantly lower (p<0.05) cases of COVID-19 than those with low malaria burden. A strong negative correlation (-0.595) between mean annual temperature and COVID-19 infection and death was observed with 14.8% variances between temperature and COVID-19 occurrence among the countries. A clear distinction was observed in the COVID-19 disease management between the developed countries (Europe and USA) and Sub-Sahara Africa. Conclusions: The study established that the wide variation in the outcome of the COVID-19 disease burden in the selected countries are attributable largely to climatic condition (temperature) and differential healthcare approaches to management of the disease. We recommend consideration and mainstreaming of these findings for urgent intervention and management of COVID-19 across these continents.

negative: Characterising the epidemic spread of Influenza A/H3N2 within a city through phylogenetics Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, it’s local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. We find trends in transmission dynamics correlated positively with trends in temperature, but not relative humidity nor school holidays. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network, while school children likely drove the spread within the remaining transmission network. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities. Author summary As shown with the current SARS-CoV-2 pandemic, respiratory diseases can quickly spread around the globe. While it can be hugely important to understand how diseases spread around the globe, local spread is most often the main driver of novel infections of respiratory diseases such as SARS-CoV-2 or influenza. We here use genetic sequence data alongside patient information to better understand what the drives the local spread of influenza by looking at the 2016/2017 influenza season in Basel, Switzerland as an example. The genetic sequence data allows us to reconstruct the how the transmission dynamics changed over the course of the season, which we correlate to changes, but not humidity or school holidays. Additionally, the genetic sequence data allows us to see how individual cases are connected. Using patient information, such as age and household status our analyses suggest that the elderly mainly transmit within their own transmission network. Additionally, they suggest that school aged children, but not pre-school aged children are important drivers of the local spread of influenza.

negative: The First 75 Days of Novel Coronavirus (SARS-CoV-2) Outbreak: Recent Advances, Prevention, and Treatment The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) outbreak has engulfed an unprepared world amidst a festive season. The zoonotic SARS-CoV-2, believed to have originated from infected bats, is the seventh member of enveloped RNA coronavirus. Specifically, the overall genome sequence of the SARS-CoV-2 is 96.2% identical to that of bat coronavirus termed BatCoV RaTG13. Although the current mortality rate of 2% is significantly lower than that of SARS (9.6%) and Middle East respiratory syndrome (MERS) (35%), SARS-CoV-2 is highly contagious and transmissible from human to human with an incubation period of up to 24 days. Some statistical studies have shown that, on average, one infected patient may lead to a subsequent 5.7 confirmed cases. Since the first reported case of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 on December 1, 2019, in Wuhan, China, there has been a total of 60,412 confirmed cases with 1370 fatalities reported in 25 different countries as of February 13, 2020. The outbreak has led to severe impacts on social health and the economy at various levels. This paper is a review of the significant, continuous global effort that was made to respond to the outbreak in the first 75 days. Although no vaccines have been discovered yet, a series of containment measures have been implemented by various governments, especially in China, in the effort to prevent further outbreak, whilst various medical treatment approaches have been used to successfully treat infected patients. On the basis of current studies, it would appear that the combined antiviral treatment has shown the highest success rate. This review aims to critically summarize the most recent advances in understanding the coronavirus, as well as the strategies in prevention and treatment.

negative: Rates of coinfection with other respiratory pathogens in patients positive for coronavirus disease 2019 (COVID‐19) OBJECTIVES: The purpose of this study was to assess coinfection rates of coronavirus disease 2019 (COVID‐19) with other respiratory infections on presentation. METHODS: This is a retrospective analysis of data from a 2 hospital academic medical centers and 2 urgent care centers during the initial 2 weeks of testing for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) , March 10, 2020 to March 23, 2020. Testing was targeted toward high‐risk patients following US Centers for Disease Control and Prevention guidelines. Demographics include age group and sex. Laboratory test results included SARS‐CoV‐2, rapid influenza A/B, and upper respiratory pathogen nucleic acid detection. Patient demographics and coinfections are presented overall and by test results with descriptive statistics. RESULTS: Complete laboratory results from the first 2 weeks of testing were available for 471 emergency department patients and 117 urgent care center patients who were tested for SARS‐CoV. A total of 51 (8.7%) patients tested positive for COVID‐19 with only 1 of these patients also testing positive for another respiratory infection. One of the patients positive for COVID‐19 also tested positive for influenza A. Among the 537 patients who were screened and tested negative for COVID‐19, there were 33 (6.1%) patients who tested positive in the upper respiratory pathogen nucleic acid detection test. CONCLUSION: In our study investigating coinfections among 51 patients testing positive for COVID‐19, 1 patient also tested positive for influenza A. Although we found limited coinfections in our emergency department and urgent care center patient populations, further research is needed to assess potential coinfection in patients with COVID‐19.

negative: Diagnostic Imaging of Chest Influenza A(H1N1) is caused by the conflict of interest between giant organisms and microorganisms. Influenza A and B viruses are single stranded RNA envelope virus composed of 890–2,341 nucleic acids in eight segmented genomes. Presently, only the virus subtypes of H1N1 and H3N2 still spread from human to human. The viruses spread and replicate under the following conditions: (1) the viruses enter the human body and duplicate there; (2) the viruses cause diseases; and (3) the viruses can easily spread from person to person. The H1N1 influenza viruses replicate is within only respiratory epithelial cells. The virus entering into the cells causes complex pathological changes of the cells. The columnar epithelial cells stop the self-synthesis of cellular component proteins. Therefore, the cells die due to their lack of necessary cell component proteins.

negative: The spread of the COVID‐19 coronavirus: Health agencies worldwide prepare for the seemingly inevitability of the COVID‐19 coronavirus becoming endemic While it is too late to confine the COVID‐19 coronovirus outbreak to China, a wealth of data spurs epidemiological and vaccine research. [Image: see text]

negative: Guide to Understanding the 2019 Novel Coronavirus

negative: Low‐dose oral interferon alpha as prophylaxis against viral respiratory illness: a double‐blind, parallel controlled trial during an influenza pandemic year BACKGROUND AND OBJECTIVE: Interferon alpha (IFNα) is a known antiviral agent. A double‐blind, placebo‐controlled clinical trial was conducted investigating the use of low‐dose oral interferon alpha for preventing acute viral respiratory illnesses. METHODS: Two hundred healthy adults aged 18–75 years were enrolled and completed weekly health data questionnaires to monitor for symptoms and impact of respiratory illness. Serum samples were tested for antibodies against influenza and other common respiratory viruses. RESULTS: Low‐dose oral IFNα prophylaxis did not reduce the incidence or impact of acute respiratory illness (ARI) or the impact of illness on daily activities. Post hoc analysis of participant subgroups, however, identified significant reductions in the incidence of ARI reported by males, those aged 50 years or more and those who received the 2009 seasonal influenza vaccine. Interferon alpha prophylaxis had a significant impact on the reporting of moderate‐to‐severe feverishness by the study population. Seropositive participants in the IFN group were more likely to report asymptomatic or mild symptoms compared with those in the placebo group who were more likely to report stronger symptoms. CONCLUSIONS: Low‐dose oral IFNα prophylaxis was not effective in limiting the overall incidence of ARI in our study population. However, there was evidence that prophylaxis reduced the severity of symptoms and had a beneficial effect in some subpopulations, including those who received the 2009 seasonal trivalent influenza vaccination.

negative: Relationship between Average Daily Temperature and Average Cumulative Daily Rate of Confirmed Cases of COVID-19 The rapid outbreak of the new Coronavirus (COVID-19) pandemic and the spread of the virus worldwide, especially in the Northern Hemisphere, have prompted various investigations about the impact of environmental factors on the rate of development of this epidemic. Different studies have called the attention to various parameters that may have influenced the spread of the virus, and in particular, the impact of climatic parameters has been emphasized. The main purpose of this study is to investigate the correlation between the average daily temperature and the rate of coronavirus epidemic growth in the infected regions. The main hypothesis object of our research is that between regions exhibiting a significant difference in the mean daily temperature, a significant difference is also observed in the average cumulative daily rate of confirmed cases, and that this does not happen if there is no significant difference in mean daily temperature. To test this research hypothesis, we carried on the case study of three regions in each of five countries and analyzed the correlation through F-test, and Independent-Samples T-Test. In all five selected countries, we found that when there is a significant difference in the daily mean temperature between two regions of a country, a significant difference exists also in the average cumulative daily rate of confirmed cases. Conversely, if there are no significant differences in the mean daily temperature of two regions in the same country, no significant difference is observed in the average cumulative daily rate of confirmed cases for these regions.

negative: A Universal Influenza A and B Duplex Real‐time RT‐PCR Assay A high throughput universal influenza A and B duplex real‐time RT‐PCR was developed to meet effectively the heightened surveillance and diagnostic needs essential in managing influenza infections and outbreaks. Primers and probes, designed to target highly conserved regions of the matrix protein of influenza A and the nucleoprotein of influenza B, were optimized using the high‐throughput LightCycler 480 II system. Analytical sensitivity and specificity were characterized using RNA transcripts diluted serially, archived non‐influenza respiratory viruses, and proficiency test samples. Eighty‐nine clinical samples were tested in parallel against existing influenza A and B monoplex assays. Once validated, the duplex assay was applied prospectively on 2,458 clinical specimens that were later subtyped. In April 2011, the emergence of an influenza B variant necessitated the inclusion of an additional modified probe for influenza B and revalidation of the revised protocol. The lower detection limits of the assay were 50 copies/PCR. There was no cross‐reactivity against any non‐influenza respiratory virus and all proficiency testing materials were identified correctly. The parallel testing revealed a 98.9% overall agreement. Routine application of the assay revealed high sensitivity and specificity for the detection of influenza A/H1N1/2009, A/H3N2 and influenza B. Assay C(q) values correlated well between the pre‐ and post‐revision protocols for influenza A (r(2) = 0.998) and B (r(2) = 0.999). The revised protocol detected three additional novel influenza B variant cases in 200 specimens reported previously as influenza B negative. This in‐house assay offers a highly sensitive and specific option for laboratories seeking to expand their influenza testing capacity. J. Med. Virol. 84:1646–1651, 2012. © 2012 Wiley Periodicals, Inc.

negative: Structure, Immunopathogenesis and Vaccines Against SARS Coronavirus A new disease, severe atypical respiratory syndrome (SARS), emerged in China in late 2002 and developed into the first epidemic of the 21st century. The disease was caused by an unknown animal coronavirus (CoV) that had crossed the species barrier through close contact of humans with infected animals, and was identified as the etiological agent for SARS. This new CoV not only became readily transmissible between humans but also was also more pathogenic. The disease spread across the world rapidly due to the air travel, and infected 8096 people and caused 774 deaths in 26 countries on 5 continents. The disease is characterized by flu-like symptoms, including high fever, malaise, cough, diarrhea, and infiltrates visible on chest radiography. The overall mortality was about 10%, but varied profoundly with age; the course of disease seemed to be milder in the pediatric age group and resulted rarely in a fatal outcome, but the mortality in the elderly was as high as 50%. Aggressive quarantine measures taken by the health authorities have successfully contained and terminated the disease transmission. As a result there are no SARS cases recorded recently. Nevertheless there is a possibility that the disease may emerge in the population with high vigor. Significant progress has been made in understanding the disease biology, pathogenesis, development of animal models, and design and evaluation of different vaccines, and these are the focus of this chapter.

negative: Explaining the Bomb-Like Dynamics of COVID-19 with Modeling and the Implications for Policy Using a Bayesian approach to epidemiological compartmental modeling, we demonstrate the bomb-like behavior of exponential growth in COVID-19 cases can be explained by transmission of asymptomatic and mild cases that are typically unreported at the beginning of pandemic events due to lower prevalence of testing. We studied the exponential phase of the pandemic in Italy, Spain, and South Korea, and found the R0 to be 2.56 (95% CrI, 2.41-2.71), 3.23 (95% CrI, 3.06-3.4), and 2.36 (95% CrI, 2.22-2.5) if we use Bayesian priors that assume a large portion of cases are not detected. Weaker priors regarding the detection rate resulted in R0 values of 9.22 (95% CrI, 9.01-9.43), 9.14 (95% CrI, 8.99-9.29), and 8.06 (95% CrI, 7.82-8.3) and assumes nearly 90% of infected patients are identified. Given the mounting evidence that potentially large fractions of the population are asymptomatic, the weaker priors that generate the high R0 values to fit the data required assumptions about the epidemiology of COVID-19 that do not fit with the biology, particularly regarding the timeframe that people remain infectious. Our results suggest that models of transmission assuming a relatively lower R0 value that do not consider a large number of asymptomatic cases can result in misunderstanding of the underlying dynamics, leading to poor policy decisions and outcomes.

negative: Reductions in Heart Failure Hospitalizations During the COVID-19 Pandemic BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has increased burden on healthcare systems with subsequent reductions in non-emergent hospitalizations and procedures. While there are widespread reports of intentional reductions in elective hospitalizations, trends in urgent or emergent hospitalizations including heart failure (HF) hospitalizations have not been adequately characterized. METHODS: We evaluated trends of HF hospitalizations before and during the COVID-19 pandemic at the University of Mississippi Medical Center using electronic health records and discharge database. We also compared HF hospitalization trends during the same time frame in 2019 to account for seasonal variation in HF presentations. RESULTS: Prior to the COVID-19 pandemic in our medical center, a mean of 30 patients per week were admitted with a principal diagnosis of HF. After the first case of COVID-19 was diagnosed in Mississippi, there was a sharp 50% decline in the number of HF hospitalizations that declined even further after a “state of emergency” was declared in Mississippi. CONCLUSIONS: Based on observations from a large academic medical center, there has been a significant reduction in the number of patients hospitalized for HF during the COVID-19 pandemic. Further investigation of these trends is warranted to determine the effects of the COVID-19 pandemic on long-term HF outcomes.

negative: Novel coronavirus takes flight from bats? Two recent studies provide initial insights into a novel coronavirus that is associated with an outbreak of human respiratory disease.

negative: Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro. Although their contribution to host defense against bacteria in vivo has been demonstrated, comparable studies of their antiviral activity in vivo are lacking. Using a mouse model deficient in activated α-defensins in the small intestine, we show that Paneth cell α-defensins protect mice from oral infection by a pathogenic virus, mouse adenovirus 1 (MAdV-1). Survival differences between mouse genotypes are lost upon parenteral MAdV-1 infection, strongly implicating a role for intestinal defenses in attenuating pathogenesis. Although differences in α-defensin expression impact the composition of the ileal commensal bacterial population, depletion studies using broad-spectrum antibiotics revealed no effect of the microbiota on α-defensin-dependent viral pathogenesis. Moreover, despite the sensitivity of MAdV-1 infection to α-defensin neutralization in cell culture, we observed no barrier effect due to Paneth cell α-defensin activation on the kinetics and magnitude of MAdV-1 dissemination to the brain. Rather, a protective neutralizing antibody response was delayed in the absence of α-defensins. This effect was specific to oral viral infection, because antibody responses to parenteral or mucosal ovalbumin exposure were not affected by α-defensin deficiency. Thus, α-defensins play an important role as adjuvants in antiviral immunity in vivo that is distinct from their direct antiviral activity observed in cell culture.

negative: Modelling the impact of COVID-19 in Australia to inform transmission reducing measures and health system preparedness Background The ability of global health systems to cope with increasing numbers of COVID-19 cases is of major concern. In readiness for this challenge, Australia has drawn on clinical pathway models developed over many years in preparation for influenza pandemics. These models have been used to estimate health care requirements for COVID-19 patients, in the context of broader public health measures. Methods An age and risk stratified transmission model of COVID-19 infection was used to simulate an unmitigated epidemic with parameter ranges reflecting uncertainty in current estimates of transmissibility and severity. Overlaid public health measures included case isolation and quarantine of contacts, and broadly applied social distancing. Clinical presentations and patient flows through the Australian health care system were simulated, including expansion of available intensive care capacity and alternative clinical assessment pathways. Findings An unmitigated COVID-19 epidemic would dramatically exceed the capacity of the Australian health system, over a prolonged period. Case isolation and contact quarantine alone will be insufficient to constrain case presentations within a feasible level of expansion of health sector capacity. Overlaid social restrictions will need to be applied at some level over the course of the epidemic to ensure that systems do not become overwhelmed, and that essential health sector functions, including care of COVID-19 patients, can be maintained. Attention to the full pathway of clinical care is needed to ensure access to critical care. Interpretation Reducing COVID-19 morbidity and mortality will rely on a combination of measures to strengthen and extend public health and clinical capacity, along with reduction of overall infection transmission in the community. Ongoing attention to maintaining and strengthening the capacity of health care systems and workers to manage cases is needed.

negative: Comparative analysis of 22 coronavirus HKU1 genomes reveals a novel genotype and evidence of natural recombination in coronavirus HKU1. We sequenced and compared the complete genomes of 22 strains of coronavirus HKU1 (CoV HKU1) obtained from nasopharyngeal aspirates of patients with respiratory tract infections over a 2-year period. Phylogenetic analysis of 24 putative proteins and polypeptides showed that the 22 CoV HKU1 strains fell into three clusters (genotype A, 13 strains; genotype B, 3 strains and genotype C, 6 strains). However, different phylogenetic relationships among the three clusters were observed in different regions of their genomes. From nsp4 to nsp6, the genotype A strains were clustered with the genotype B strains. For nsp7 and nsp8 and from nsp10 to nsp16, the genotype A strains were clustered with the genotype C strains. From hemagglutinin esterase (HE) to nucleocapsid (N), the genotype B strains were clustered closely with the genotype C strains. Bootscan analysis showed possible recombination between genotypes B and C from nucleotide positions 11,500 to 13,000, corresponding to the nsp6-nsp7 junction, giving rise to genotype A, and between genotypes A and B from nucleotide positions 21,500 to 22,500, corresponding to the nsp16-HE junction, giving rise to genotype C. Multiple alignments further narrowed the sites of crossover to a 143-bp region between nucleotide positions 11,750 and 11,892 and a 29-bp region between nucleotide positions 21,502 and 21,530. Genome analysis also revealed various numbers of tandem copies of a perfect 30-base acidic tandem repeat (ATR) which encodes NDDEDVVTGD and various numbers and sequences of imperfect repeats in the N terminus of nsp3 inside the acidic domain upstream of papain-like protease 1 among the 22 genomes. All 10 CoV HKU1 strains with incomplete imperfect repeats (1.4 and 4.4) belonged to genotype A. The present study represents the first evidence for natural recombination in coronavirus associated with human infection. Analysis of a single gene is not sufficient for the genotyping of CoV HKU1 strains but requires amplification and sequencing of at least two gene loci, one from nsp10 to nsp16 (e.g., pol or helicase) and another from HE to N (e.g., spike or N). Further studies will delineate whether the ATR is useful for the molecular typing of CoV HKU1.

negative: Transmission potential of the novel coronavirus (COVID-19) onboard the Diamond Princess Cruises Ship, 2020 An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January-February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ~11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1-7). Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of Rt reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.

negative: CoViD-19 and Ortho and Trauma Surgery: the Italian Experience.

negative: Vietnam's war on flu Having suffered heavily from avian influenza in 2004, Vietnam might now be brewing the next human flu pandemic. Yet, as Peter Aldhous discovers, local researchers don't have the resources to investigate the risk properly.

negative: Managing community-acquired pneumonia during flu season. The clinical findings of influenza overlap those of community-acquired bacterial pneumonia (CABP), and influenza infection can be complicated by bacterial infections. Reviewed here are the epidemiology, pathophysiology, diagnosis, and management of community-acquired pneumonia (CAP) with special emphasis on considerations during influenza season.

negative: Public Masking: An Urgent Need to Revise Global Policies to Protect against COVID-19

negative: Has mortality due to other causes increased during the Covid-19 pandemic? Early evidence from England and Wales Background: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the novel coronavirus has also been associated with an increase in deaths in England and Wales for those who have not contracted the disease. Reasons behind this may include avoiding visits to hospitals or GPs, and the effects of the lockdown. Methods: I used weekly ONS data on the number of deaths that did not involve covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a differences-in-differences econometric approach to study whether there was a relative increase in non-covid-19 deaths during the pandemic, compared to a control. As an additional approach, an interrupted time series model was also used. Results: Results suggest that there were an additional 531 non-covid-19 deaths in England and Wales since the outbreak of the pandemic, compared to what would have otherwise been expected [diff-in-diff interaction coeff: 531.11; 95%CI: 125.65 to 936.57]. This is confirmed by the interrupted time series model. Discussion: The health effects of covid-19 do not seem to be limited only to patients suffering from the disease, as the number of deaths for those who did not contract covid-19 has also demonstrated an absolute and relative increase. Analysing the cause of death for non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.

negative: Advances in disease diagnosis, vaccine development and other emerging methods to control pathogens in aquaculture Disease is still regarded as a major constraint to aquaculture production globally. Rapid disease diagnosis and vaccination play a huge part in the control of bacterial diseases, and there has been significant progress in both of these areas. This chapter considers the limitations of existing methods and reviews recent advances made in pathogen detection technologies and vaccine development methodologies. Future directions are discussed, including nanotechnology and reversed vaccinology.

negative: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection: let the virus be its own demise There has been a collaborative global effort to construct novel therapeutic and prophylactic approaches to SARS-CoV-2 management. Although vaccine development is crucial, acute management of newly infected patients, especially those with severe acute respiratory distress syndrome, is a priority. Herein we describe the rationale and potential of repurposing a dual plasmid, Vigil (pbi-shRNA(furin)-GM-CSF), now in Phase III cancer trials, for the treatment of and, in certain circumstances, enhancement of the immune response to SARS-CoV-2.

negative: Time variations in the transmissibility of pandemic influenza in Prussia, Germany, from 1918–19 BACKGROUND: Time variations in transmission potential have rarely been examined with regard to pandemic influenza. This paper reanalyzes the temporal distribution of pandemic influenza in Prussia, Germany, from 1918–19 using the daily numbers of deaths, which totaled 8911 from 29 September 1918 to 1 February 1919, and the distribution of the time delay from onset to death in order to estimate the effective reproduction number, Rt, defined as the actual average number of secondary cases per primary case at a given time. RESULTS: A discrete-time branching process was applied to back-calculated incidence data, assuming three different serial intervals (i.e. 1, 3 and 5 days). The estimated reproduction numbers exhibited a clear association between the estimates and choice of serial interval; i.e. the longer the assumed serial interval, the higher the reproduction number. Moreover, the estimated reproduction numbers did not decline monotonically with time, indicating that the patterns of secondary transmission varied with time. These tendencies are consistent with the differences in estimates of the reproduction number of pandemic influenza in recent studies; high estimates probably originate from a long serial interval and a model assumption about transmission rate that takes no account of time variation and is applied to the entire epidemic curve. CONCLUSION: The present findings suggest that in order to offer robust assessments it is critically important to clarify in detail the natural history of a disease (e.g. including the serial interval) as well as heterogeneous patterns of transmission. In addition, given that human contact behavior probably influences transmissibility, individual countermeasures (e.g. household quarantine and mask-wearing) need to be explored to construct effective non-pharmaceutical interventions.

negative: Chapter Eleven Communicating During a Public Health Crisis “Communicating during a Public Health Crisis,” examines how communicating to the public and media during a public health or safety emergency is different. In a serious crisis, all affected people take in information differently, process information differently and act on information differently. This chapter incorporates the Centers for Disease Control and Prevention’s (CDC) best advice for communicating during a public health crisis, including infectious disease outbreaks, bioterrorism, chemical emergencies, natural disasters, nuclear accidents and radiation releases and explosions. This chapter also explores the growing role of social media that is now being used for a variety of traditional and new purposes from distress calls to disease surveillance.

negative: Utilization of the respiratory virus multiplex reverse transcription-polymerase chain reaction test for adult patients at a Korean tertiary care center BACKGROUND/AIMS: Respiratory viruses (RVs) are considered to be important respiratory pathogens in adult patients, and the multiplex reverse transcription-polymerase chain reaction (RT-PCR) test is used frequently in adult patients with respiratory infections. However, clinical data regarding utilization of the multiplex RT-PCR test for RVs are lacking. METHODS: We investigated the utilization of the multiplex RT-PCR test for RVs at Chung-Ang University Hospital in Seoul, Korea, between January 2012 and April 2013. RESULTS: During the study period, the multiplex RT-PCR test was performed for 291 adult patients. The test frequency was 4.9% of rapid influenza antigen detection tests and 0.8% of respiratory bacterial culture studies. A turnaround time of < 48 hours was observed in 25.9% of positive tests. Most of the tests were performed for admitted patients (97.9%) with a community-acquired infection (84.2%) during the flu season (82.5%). RVs were detected in 81 of 291 cases (27.8%). The RV positivity rates for community- and hospital-acquired infections did not differ (28.6% vs. 23.9%, p = 0.52). Of 166 patients with pneumonia, 44 (26.5%) had a viral infection. Among the patients with RV-associated pneumonia, an RV other than influenza was detected in 20 patients (45.4%). CONCLUSIONS: The multiplex RT-PCR test for RVs was infrequently performed at a tertiary care center, and the test results were often reported late. The test was most often performed for admitted adult patients with community-acquired infections during the flu season. The utilization of multiplex RT-PCR testing for RVs in current clinical practice should be improved.

negative: Coronavirus disease 2019 in an orthotopic liver transplant recipient living with human immunodeficiency virus Coronavirus disease 2019 (COVID-19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with flu-like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID-19-infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID-19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well-controlled HIV who successfully recovered from a mild, flu-like illness attributed to SARS-CoV-2.

negative: Global years of life lost to COVID-19 Understanding the mortality impact of COVID-19 requires not only counting the dead, but analyzing how premature the deaths are. We calculate years of life lost (YLL) across 42 countries due to COVID-19 attributable deaths, and also conduct an analysis based on estimated excess deaths. As of June 13th 2020, YLL in heavily affected countries are 2 to 6 times the average seasonal influenza; over two thirds of the YLL result from deaths in ages below 75 and one quarter from deaths below 55; and men have lost 47% more life years than women. The results confirm the large mortality impact of COVID-19 among the elderly. They also call for heightened awareness in devising policies that protect vulnerable demographics losing the largest number of life-years.

negative: Machine Learning the Phenomenology of COVID-19 From Early Infection Dynamics We present a robust data-driven machine learning analysis of the COVID-19 pandemic from its early infection dynamics, specifically infection counts over time. The goal is to extract actionable public health insights. These insights include the infectious force, the rate of a mild infection becoming serious, estimates for asymtomatic infections and predictions of new infections over time. We focus on USA data starting from the first confirmed infection on January 20 2020. Our methods reveal significant asymptomatic (hidden) infection, a lag of about 10 days, and we quantitatively confirm that the infectious force is strong with about a 0.14% transition from mild to serious infection. Our methods are efficient, robust and general, being agnostic to the specific virus and applicable to different populations or cohorts.

negative: Mouse adaptation of the H9N2 avian influenza virus causes the downregulation of genes related to innate immune responses and ubiquitin-mediated proteolysis in mice H9N2 avian influenza viruses sporadically infect humans worldwide. These viruses have also contributed internal genes to H5N1, H5N6, H7N9, and H10N8 viruses, which have been isolated from humans with infections and are a substantial public health threat. To investigate the potential pathogenic mechanism of the H9N2 virus, we performed serial lung-to-lung passage of an avirulent H9N2 avian influenza virus (A/Chicken/Shandong/416/2016 [SD/416]) in mice to increase the pathogenicity of this virus. We generated a mouse-adapted (MA) virus that exhibited increased viral titers in the lungs, caused severe lung damage in mice, and induced body weight loss in mice; however, the avirulent parental virus did not cause any clinical symptoms in infected mice. Global gene expression analysis was performed and indicated that the transcriptional responses of these viruses were distinct. The lungs of mice infected with the MA virus exhibited the downregulation of genes related to innate immunity and ubiquitin-mediated proteolysis, which was not seen in infections with the avirulent parental virus. These data indicated that the MA virus might evade immune surveillance and changed its replication capacity to increase the viral replication level and pathogenicity. Our study demonstrates that host factors play an important role in the adaptive evolution of influenza virus in new hosts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00430-020-00656-4) contains supplementary material, which is available to authorized users.

negative: Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period There is an urgent need to project how transmission of the novel betacoronavirus SARS-CoV-2 will unfold in coming years. These dynamics will depend on seasonality, the duration of immunity, and the strength of cross-immunity to/from the other human coronaviruses. Using data from the United States, we measured how these factors affect transmission of human betacoronaviruses HCoV-OC43 and HCoV-HKU1. We then built a mathematical model to simulate transmission of SARS-CoV-2 through the year 2025. We project that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after an initial pandemic wave. We summarize the full range of plausible transmission scenarios and identify key data still needed to distinguish between them, most importantly longitudinal serological studies to determine the duration of immunity to SARS-CoV-2.

negative: Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period It is urgent to understand the future of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for betacoronaviruses OC43 and HKU1 from time series data from the USA to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained since a resurgence in contagion could be possible as late as 2024.

negative: RT-PCR testing to detect a COVID-19 outbreak in Austria: rapid, accurate and early diagnosis in primary care (The REAP study) Background Delay in COVID-19 detection has led to a major pandemic. We report rapid early detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR), comparing it to the serostatus of convalescent infection, at an Austrian National Sentinel Surveillance Practice in an isolated ski-resort serving a population of 22,829 people. Methods Retrospective dataset of all 73 patients presenting with mild to moderate flu-like symptoms to a sentinel practice in the ski-resort of Schladming-Dachstein, Austria, between 24 February and 03 April, 2020. We split the outbreak in two halves, by dividing the period from the first to the last case by two, to characterise the following three cohorts of patients with confirmed infection: people with reactive RT-PCR presenting during the first half (early acute infection) vs. those presenting in the second half (late acute), and people with non-reactive RT-PCR (late convalescent). For each cohort we report the number of cases detected, the accuracy of RT-PCR and the duration of symptoms. We also report multivariate regression of 15 clinical symptoms as covariates, comparing all people with convalescent infection to those with acute infection. Findings All 73 patients had SARS-CoV-2 RT-PCR testing. 22 patients were diagnosed with COVID-19, comprising: 8 patients presenting early acute, and 7 presenting late acute and 7 late convalescent respectively; 44 patients tested SARS-COV-2 negative, and 7 were excluded. RT-PCR sensitivity was high (100%) among acute presenters, but dropped to 50% in the second half of the outbreak; specificity was 100%. The mean duration of symptoms was 2 days (range 1-4) among early acute presenters, and 4.4 days (1-7) among late acute and 8 days (2-12) among late convalescent presenters respectively. Convalescent infection was only associated with loss of taste (ORs=6.02;p=0.047). Acute infection was associated with loss of taste (OR=571.72;p=0.029), nausea and vomiting (OR=370.11;p=0.018), breathlessness (OR=134.46;p=0.049), and myalgia (OR=121.82;p=0.032); but not loss of smell, fever or cough. Interpretation RT-PCR rapidly and reliably detects early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. RT-PCR testing in primary care should be prioritised for effective COVID-19 prevention and control.

negative: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020 Importance: Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective: To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population: This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures: Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results: There were approximately 781â¯000 total deaths in the United States from March 1 to May 30, 2020, representing 122â¯300 (95% prediction interval, 116â¯800-127â¯000) more deaths than would typically be expected at that time of year. There were 95â¯235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance: Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.

negative: Are there any differences in clinical and laboratory findings on admission between H1N1 positive and negative patients with flu-like symptoms? BACKGROUND: The World Health Organization alert for the H1N1 influenza pandemic led to the implementation of certain measures regarding admission of patients with flu-like symptoms. All these instructions were adopted by the Greek National Health System. The aim of this study was to retrospectively examine the characteristics of all subjects admitted to the Unit of Infectious Diseases with symptoms indicating H1N1 infection, and to identify any differences between H1N1 positive or negative patients. Patients from the ED (emergency department) with flu-like symptoms (sore throat, cough, rhinorhea, or nasal congestion) and fever >37.5°C were admitted in the Unit of Infectious diseases and gave pharyngeal or nasopharyngeal swabs. Swabs were tested with real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR). FINDINGS: Patients were divided into two groups. Group A comprised 33 H1N1 positive patients and Group B (control group) comprised of 27 H1N1 negative patients. The two groups did not differ in terms of patient age, co-morbidities, length of hospitalization, temperature elevation, hypoxemia, as well as renal and liver function. There were also no significant differences in severity on admission. C-reactive protein (CRP) (mean 12.8 vs. 5.74) and white blood count (WBC) (mean 10.528 vs. 7.114) were significantly higher in group B than in group A upon admission. Obesity was noted in 8 patients of Group A (mean 31.67) and 14 patients of Group B (mean 37.78). Body mass index (BMI) was lower in H1N1 positive than in H1N1 negative patients (mean 31.67 vs. 37.78, respectively; p = 0.009). CONCLUSIONS: The majority of patients in both groups were young male adults. CRP, WBC and BMI were higher among H1N1 negative patients. Finally, clinical course of patients in both groups was mild and uneventful.

negative: Infodemiological Study Using Google Trends on Coronavirus Epidemic in Wuhan, China The recent emergence of a new coronavirus (COVID-19) has gained a high cover in public media and worldwide news. The virus has caused a viral pneumonia in tens of thousands of people in Wuhan, a central city of China. This short paper gives a brief introduction on how the demand for information on this new epidemic is reported through Google Trends. The reported period is 31 December 2020 to 20 March 2020. The authors draw conclusions on current infodemiological data on COVID-19 using three main search keywords: coronavirus, SARS and MERS. Two approaches are set. First is the worldwide perspective, second - the Chinese one, which reveals that in China this disease in the first days was more often referred to SARS then to general coronaviruses, whereas worldwide, since the beginning, it is more often referred to coronaviruses.

negative: Effect of avian influenza A H5N1 infection on the expression of microRNA-141 in human respiratory epithelial cells BACKGROUND: Avian influenza remains a serious threat to human health. The consequence of human infection varies markedly among different subtypes of avian influenza viruses. In addition to viral factors, the difference in host cellular response is likely to play a critical role. This study aims at elucidating how avian influenza infection perturbs the host’s miRNA regulatory pathways that may lead to adverse pathological events, such as cytokine storm, using the miRNA microarray approach. RESULTS: The results showed that dysregulation of miRNA expression was mainly observed in highly pathogenic avian influenza A H5N1 infection. We found that miR-21*, miR-100*, miR-141, miR-574-3p, miR-1274a and miR1274b were differentially expressed in response to influenza A virus infection. Interestingly, we demonstrated that miR-141, which was more highly induced by H5N1 than by H1N1 (p < 0.05), had an ability to suppress the expression of a cytokine - transforming growth factor (TGF)-β2. This was supported by the observation that the inhibitory effect could be reversed by antagomiR-141. CONCLUSIONS: Since TGF-β2 is an important cytokine that can act as both an immunosuppressive agent and a potent proinflammatory molecule through its ability to attract and regulate inflammatory molecules, and previous report showed that only seasonal influenza H1N1 (but not the other avian influenza subtypes) could induce a persistent expression of TGF-β2, we speculate that the modulation of TGF-β2 expression by different influenza subtypes via miR-141 might be a critical step for determining the outcome of either normal or excessive inflammation progression.

negative: Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013 The Burden of Communicable Diseases in Europe (BCoDE) study aimed to calculate disability-adjusted life years (DALYs) for 31 selected diseases in the European Union (EU) and European Economic Area (EEA). Methods: DALYs were estimated using an incidence-based and pathogen-based approach. Incidence was estimated through assessment of data availability and quality, and a correction was applied for under-estimation. Calculation of DALYs was performed with the BCoDE software toolkit without applying time discounting and age-weighting. Results: We estimated that one in 14 inhabitants experienced an infectious disease episode for a total burden of 1.38 million DALYs (95% uncertainty interval (UI): 1.25–1.5) between 2009 and 2013; 76% of which was related to the acute phase of the infection and its short-term complications. Influenza had the highest burden (30% of the total burden), followed by tuberculosis, human immunodeficiency virus (HIV) infection/AIDS and invasive pneumococcal disease (IPD). Men had the highest burden measured in DALYs (60% of the total), adults 65 years of age and over had 24% and children less than 5 years of age had 11%. Age group-specific burden showed that infants (less than 1 year of age) and elderly people (80 years of age and over) experienced the highest burden. Conclusions: These results provide baseline estimates for evaluating infectious disease prevention and control strategies. The study promotes an evidence-based approach to describing population health and assessing surveillance data availability and quality, and provides information for the planning and prioritisation of limited resources in infectious disease prevention and control.

negative: National Consumption of Antimalarial Drugs and COVID-19 Deaths Dynamics : an Ecological Study COVID-19 (Coronavirus Disease-2019) is an international public health problem with a high rate of severe clinical cases. Several treatments are currently being tested worldwide. This paper focuses on anti-malarial drugs such as chloroquine or hydroxychloroquine, which have been currently reviewed by a systematic study as a good potential candidate and that has been reported as the most used treatment by a recent survey of physicians. We compare the dynamics of COVID-19 death rates in countries using anti-malaria drugs as a treatment from the start of the epidemic versus countries that do not, the day of the 3rd death and the following 10 days. We show that the first group have a much slower dynamic in death rates that the second group. This univariate analysis is of course only one additional piece of evidence in the debate regarding the efficiency of anti-malaria drugs, and it is also limited as the two groups certainly have other systemic differences in the way they responded to the pandemic, in the way they report death or in their population that better explain differences in dynamics (systematic differences that may also explain their choice to rely on anti-malaria drugs in the first place). Nevertheless, the difference in dynamics is so striking that we believe that the urgency context commands presenting the univariate analysis before delving into further analysis. In the end, this data might ultimately be either a piece of evidence in favor or anti-malaria drugs or a stepping stone in understanding further what other ecological aspects place a role in the dynamics of COVID-19 deaths.

negative: Azithromycin and COVID-19: Prompt early use at first signs of this infection in adults and children, an approach worthy of consideration The devastating effects of the coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to urgent attempts to find effective therapeutic agents for inpatient and outpatient treatment of COVID-19. Initial enthusiasm for the combination of hydroxychloroquine and azithromycin has abated. However, as a result of positive clinical experience with azithromycin used alone during the first few days of the flu-like illness caused by this coronavirus, we recommend formal clinical trials using azithromycin early in the course of a COVID-19 infection. There is one clinical trial initiated, the individually randomized, telemedicine-based, "Azithromycin for COVID-19 Treatment in Outpatients Nationwide" based at the University of California San Francisco. This placebo-controlled trial is designed to determine the efficacy of a single 1.2-g dose of oral azithromycin to prevent COVID-19 patient progression to hospitalization. We recommend formal clinical trials of azithromycin in its prepackaged form at the first sign of COVID-19 infection in adults and children, using an initial adult dose of 500 mg followed by 250 mg per day for 4 days, a total cumulative dose of 1.5 g, and for children 5 to 18 years of age, 10 mg/kg on the first day followed by 5 mg/kg for 4 days.

negative: Visualising the expansion and spread of coronavirus disease 2019 by cartograms Coronavirus disease 2019 (COVID-19) has emerged as a growing focus of global attention and a critical factor in public-health decision making. Towards fighting the COVID-19 outbreak, countries worldwide and international organisations have taken various actions, including promoting the transparency of and public access to disease data. In such public communications, maps have played an important role in that a map is worth a thousand words. Most of these have taken the form of a choropleth map. Here, we propose employing cartograms to visualise both the expansion and spread of COVID-19. We designed a combination of six circular cartograms containing the data of confirmed cases every 48 hours from 24 January to 3 February 2020. Such a design conveys both spatial and temporal information more intuitively and efficiently, so it can be expected to facilitate better public participation in the fight against COVID-19.

negative: Climate affects global patterns of COVID-19 early outbreak dynamics Environmental factors, including seasonal climatic variability, can strongly impact on spatio-temporal patterns of infectious disease outbreaks, but relationships between Covid-19 dynamics and climate remain controversial. We assessed the impact of temperature and humidity on the global patterns of Covid-19 early outbreak dynamics during January-March 2020. Here we show that Covid-19 growth rates peaked in temperate regions of the Northern Hemisphere with mean temperature of ~5 C, and specific humidity of 4-6 g/m3 during the outbreak period, while they were lower both in warmer/wetter and colder/dryer regions. Relationships between Covid-19 and climate were robust to the potential confounding effects of air pollution and socio-economic variables, including population size, density and health expenditure. The strong relationship between local climate and Covid-19 growth rates suggests the possibility of seasonal variation in the spatial pattern of outbreaks, with temperate regions of the Southern Hemisphere becoming at particular risk of severe outbreaks during the austral autumn-winter.

negative: Public Masking: An Urgent Need to Revise Global Policies to Protect against COVID-19 Public Masking: An Urgent Need to Revise Global Policies to Protect against Novel Coronavirus Disease (COVID-19).

negative: MARKOVIAN RANDOM WALK MODELING AND VISUALIZATION OF THE EPIDEMIC SPREAD OF COVID-19 The epidemic spread of CoVID-19 has resulted in confirmed cases of viral respiratory illness in more than 1.4 million people around the world as of April 7th, 2020. However, different regions have experienced the spread of this disease differently. Here, we develop a Markovian random-walk spatial extension of a quarantine-enhanced SIR model to measure, visualize and forecast the effect of susceptible population density, testing rate, and social distancing and quarantine policies on epidemic spreading. The model is used to simulate the spread of CoVID-19 in the regions of Hubei, China; South Korea; Iran; and Spain. The model allows for evaluating the results of different policies both quantitatively and visually as means of better understanding and controlling the spread of the disease.

negative: Silver Lining of COVID-19: heightened global interest in pneumococcal and influenza vaccines, an infodemiology study BACKGROUND: Health-seeking behaviors change during pandemics and may increase with regard to illnesses with symptoms similar to the pandemic. The global reaction to COVID-19 may drive interest in vaccines for other diseases. OBJECTIVES: Our study investigated the correlation between global online interest in COVID-19 and interest in CDC-recommended routine vaccines. DESIGN, SETTINGS, MEASUREMENTS: This infodemiology study used Google Trends data to quantify worldwide interest in COVID-19 and CDC-recommended vaccines using the unit search volume index (SVI), which estimates volume of online search activity relative to highest volume of searches within a specified period. SVIs from December 30, 2019 to March 30, 2020 were collected for “coronavirus (Virus)” and compared with SVIs of search terms related to CDC-recommended adult vaccines. To account for seasonal variation, we compared SVIs from December 30, 2019 to March 30, 2020 with SVIs from the same months in 2015 to 2019. We performed country-level analyses in ten COVID-19 hotspots and ten countries with low disease burden. RESULTS: There were significant positive correlations between SVIs for “coronavirus (Virus)” and search terms for pneumococcal (R=0.89, p<0.0001) and influenza vaccines (R=0.93, p<0.0001) in 2020, which were greater than SVIs for the same terms in 2015-2019 (p= 0.005, p<0.0001, respectively). Eight in ten COVID-19 hotspots demonstrated significant positive correlations between SVIs for coronavirus and search terms for pneumococcal and influenza vaccines. LIMITATIONS: SVIs estimate relative changes in online interest and do not represent for people with no Internet access. CONCLUSION: A peak in worldwide interest in pneumococcal and influenza vaccines coincided with the COVID-19 pandemic in February and March 2020. Trends are likely not seasonal in origin and may be driven by Covid-19 hotspots. Global events may change public perception about the importance of vaccines. Our findings may herald higher demand for pneumonia and influenza vaccines in the upcoming season.

negative: Abstract for the 8th International congress, Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases

negative: Influenza risk perception and travel-related health protection behavior in the US: Insights for the aftermath of the COVID-19 outbreak Abstract Influenza is a contagious virus affecting both one's health and economic productivity. This study evaluates uses a survey of 2168 individuals across the U.S. Ordered logit regressions are used to model risk perception and generalized ordered logit regressions are used to model risk mitigation travel-related decisions. Models are estimated for three influenza outbreak scenarios, specifically an individual's travel-related: 1) risk perceptions, 2) risk mitigation decisions when infected and the individual wants to prevent spreading it, and may want treatment, and 3) risk mitigation decisions when not infected and the individual wants to reduce exposure. Risk perception results show that a recent personal experience with influenza-like symptoms and being female significantly increased risk perception at mandatory and medical trip locations. Risk mitigation model results show that males are less likely to alter their travel patterns in response to the possible spreading of the virus or increasing exposure. Knowing the difference between influenza and the stomach flu is more influential in reducing travel than a recent influenza experience in one's household. Individuals proactive with their health (i.e., receive the vaccine, have health insurance) are also proactive in seeking medical attention and reducing influenza spread. Lastly, aligned with the Protection Motivation Theory, individuals reduce travel to locations in which they perceived medium or high risk. However, increased risk perceived at one's work location did not significantly reduce travel. The findings provide insight into the risk perception and mitigation behavior of the American public during the COVID-19 pandemic and after restrictions are lifted.

negative: SARS-CoV-2 coinfections: Could influenza and the common cold be beneficial? The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread around the world, causing serious illness and death and creating a heavy burden on the healthcare systems of many countries. Since the virus first emerged in late November 2019, its spread has coincided with peak circulation of several seasonal respiratory viruses, yet some studies have noted limited coinfections between SARS-CoV-2 and other viruses. We use a mathematical model of viral coinfection to study SARS-CoV-2 coinfections, finding that SARS-CoV-2 replication is easily suppressed by many common respiratory viruses. According to our model, this suppression is because SARS-CoV-2 has a lower growth rate (1.8/d) than the other viruses examined in this study. The suppression of SARS-CoV-2 by other pathogens could have implications for the timing and severity of a second wave.

negative: Warned, but Not Well Armed: Preventing Viral Upper Respiratory Infections in Households ABSTRACT The purpose of this state‐of‐the‐science review was to identify strategies and household‐level interventions for public health nurses to help prevent the acquisition and spread of viral upper respiratory infections (URI) in the community. Even though viral URI are a major global economic and social problem, surprisingly little research has been conducted to attempt to prevent them or reduce their transmission, probably because URI (with the exception of epidemic influenza) are generally considered to be mild and self‐limited. Based on the research to date, public health nurses can use several promising strategies for prevention: (a) provide more tailored educational messages regarding preventive strategies such as vaccination, hand hygiene, spatial separation of infected household members, avoidance of antibiotics to treat viral URI, and environmental cleaning (e.g., for toys or other shared items), which are delivered personally rather than passively (e.g., pamphlets placed in a waiting room); (b) use each patient encounter in any setting to encourage influenza vaccination for relevant risk groups; (c) encourage use of alcohol hand sanitizers by household members during the cold and flu season; and (d) provide opportunities for skill development for adult and child household members (e.g., cover your cough, when to seek care or an antibiotic).

negative: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain in the host population. In turn, the virus can never completely eliminate the host population, because evolutionarily such an event is a dead end for the virus as an obligate intracellular parasite. A certain existential balance exists in the virus-host relationship. Against this backdrop, viral epidemics and pandemics only become manifest and egregious to human beings when tens and hundreds of thousands of people die and the question emerges what caused the high mortality peaks on the death chart. The answer seems clear; the emerging strain of the virus is new to the host population, and new mutations of the virus and natural selection will lead to a survival of only genetically resistant individuals in a host population. The dangers inherent to a novel virus are due to new features generally inthe molecular structure of proteins, which enable the virus to infect the cells of the host organism more intensively, dramatically challenging host immunity, and thus be transmitted more readily in the host population. In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In fact, only two scenarios will occur simultaneously in the very near future: people who are genetically resistant to the virus will get sick, recover, and develop immunity, while people who are sensitive to the virus will need drugs and vaccines, which will have to be researched and developed if they are to recover. If the pandemic does not stop, in a few decades it is anticipated that SARS-CoV-2 will become as safe as the four non-severe acute respiratory syndrome human coronaviruses (HCoV-NL63, HCoV-HKU1, HCoV-OC43, and HCoV-229E) currently circulating but causing low mortality in the human population.

negative: The evolution of human influenza A viruses from 1999 to 2006: A complete genome study BACKGROUND: Knowledge about the complete genome constellation of seasonal influenza A viruses from different countries is valuable for monitoring and understanding of the evolution and migration of strains. Few complete genome sequences of influenza A viruses from Europe are publicly available at the present time and there have been few longitudinal genome studies of human influenza A viruses. We have studied the evolution of circulating human H3N2, H1N1 and H1N2 influenza A viruses from 1999 to 2006, we analysed 234 Danish human influenza A viruses and characterised 24 complete genomes. RESULTS: H3N2 was the prevalent strain in Denmark during the study period, but H1N1 dominated the 2000–2001 season. H1N2 viruses were first observed in Denmark in 2002–2003. After years of little genetic change in the H1N1 viruses the 2005–2006 season presented H1N1 of greater variability than before. This indicates that H1N1 viruses are evolving and that H1N1 soon is likely to be the prevalent strain again. Generally, the influenza A haemagglutinin (HA) of H3N2 viruses formed seasonal phylogenetic clusters. Different lineages co-circulating within the same season were also observed. The evolution has been stochastic, influenced by small "jumps" in genetic distance rather than constant drift, especially with the introduction of the Fujian-like viruses in 2002–2003. Also evolutionary stasis-periods were observed which might indicate well fit viruses. The evolution of H3N2 viruses have also been influenced by gene reassortments between lineages from different seasons. None of the influenza genes were influenced by strong positive selection pressure. The antigenic site B in H3N2 HA was the preferred site for genetic change during the study period probably because the site A has been masked by glycosylations. Substitutions at CTL-epitopes in the genes coding for the neuraminidase (NA), polymerase acidic protein (PA), matrix protein 1 (M1), non-structural protein 1 (NS1) and especially the nucleoprotein (NP) were observed. The N-linked glycosylation pattern varied during the study period and the H3N2 isolates from 2004 to 2006 were highly glycosylated with ten predicted sequons in HA, the highest amount of glycosylations observed in this study period. CONCLUSION: The present study is the first to our knowledge to characterise the evolution of complete genomes of influenza A H3N2, H1N1 and H1N2 isolates from Europe over a time period of seven years from 1999 to 2006. More precise knowledge about the circulating strains may have implications for predicting the following season strains and thereby better matching the vaccine composition.

negative: Severe flu management: a point of view Annual flu seasons are typically characterized by changes in types and subtypes of influenza, with variations in terms of severity. Despite remarkable improvements in the prevention and management of patients with suspected or laboratory-confirmed diagnosis of influenza, annual seasonal influenza continues to be associated with a high morbidity and mortality. Admission to the intensive care unit is required for patients with severe forms of seasonal influenza infection, with primary pneumonia being present in most of the cases. This review summarizes the most recent knowledge on the diagnosis and treatment strategies in critically ill patients with influenza, focused on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, and supportive measures. The review focuses on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, supportive measures and relevant existing evidence, in order to provide the non-expert clinician a useful overview. An enhanced understanding of current diagnostic and treatment aspects of influenza infection can contribute to improve outcomes and reduce mortality among ICU patients with influenza.

negative: Chapter 3 Applications of Molecular Tools to Infectious Disease Epidemiology Publisher Summary Molecular tools enhance outbreak investigation and surveillance, facilitate description of the transmission system, and increase understanding of the epidemiology. Molecular tools enhance case definitions, increasing specificity and reducing misclassification, and are now a standard tool in outbreak investigations. Although it is assumed during an outbreak that a single microbe is causing the clinical symptoms, it is possible that a microbe of the same genus and species but different strain is causing disease during the same time period. Molecular typing can distinguish between outbreak and nonoutbreak strains. Molecular tools also facilitate estimating parameters key to understanding the transmission system, including the incidence, prevalence, transmission probability, duration of carriage, effective dose, and probability of effective contact. Molecular tools enable one to trace the dissemination of a particular subtype across time and space and thus develop theories of transmission and dissemination, determine the origin of an epidemic and test theories about reservoirs and evolution of a particular pathogen, follow the emergence of new infections as they cross species, testing the hypotheses about the apparent transmissibility and rate of evolution, and follow mobile genetic elements conferring antimicrobial resistance or virulence between strains within a species or between species, and so develop theories about evolution and transmission within the populations of pathogens.

negative: Influenza vaccination in the COVID-19 era Influenza spreads globally annually with significant paediatric and adult attack rates and considerable morbidity, mortality and the exacerbation of extant chronic disease. In the northern and southern hemispheres, outbreaks occur mainly in the respective winter seasons. Influenza vaccination is available but only partially effective. In the absence of a vaccine, in winter, novel coronavirus COVID-19 will also circulate in parallel with seasonal influenza. Thus far it appears that with the current strains of these two viruses, the clinical outcome of co-infection is not significantly worse than infection with COVID-19 alone. However, several strains of influenza circulate, including strains still to come. Similarly, COVID-19 has several strains, with probably more to come. This paper discusses these issues and estimates ideal minimum influenza vaccination coverage based on an estimated influenza Basic Reproduction Number (R0) of 0.9-2.1 so as to obtain herd immunity or approach it. There is a strong argument for attempting near universal population coverage with the annual influenza vaccine leading up to next winter.

negative: Molecular epidemiology of influenza, RSV, and other respiratory infections among children in Qatar: A six years report (2012–2017) Abstract Background Studies on the etiology of respiratory infections among children in Qatar and surrounding countries are limited. Objectives To describe the prevalence and seasonality of RSV, influenza, and other respiratory pathogens among children in Qatar. Methods We retrospectively collected and analyzed data of 33,404 children (<15 years) presented with influenza-like illness from 2012 to 2017. Results At least one respiratory pathogen was detected in 26,138 (78%) of patients. Together, human rhinoviruses (HRV), respiratory syncytial virus (RSV), and influenza viruses comprised nearly two-thirds of all cases, affecting 24%, 19.7%, and 18.5%, respectively. A prevalence of 5-10% was recorded for adenovirus, parainfluenza viruses (PIVs), human bocavirus (HboV), and human coronaviruses (HCoVs). Human metapneumovirus (HMPV), enteroviruses, M. pneumonia, and parechovirus had prevalences below 5%. While RSV, influenza, and HMPV exhibited strong seasonal activity in the winter, HRV was active during low RSV and influenza circulation. The burden of RSV exceeds that of influenza among young age groups, whereas influenza correlated positively with age. Further, HRV, adenovirus, influenza, and RSV infection rates varied significantly between male and females. Conclusion This comprehensive multi-year study provides insights into the etiology of ILI among children in Qatar, which represents the Gulf region. Our results reinforce the significance of active surveillance of respiratory pathogens to improve infection prevention and control strategies, particularly among children.

negative: Conservation of T cell epitopes between seasonal influenza viruses and the novel influenza A H7N9 virus A novel avian influenza A (H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses (compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.

negative: Crushing the curve, the role of national and international institutions and policy makers in COVID-19 pandemic Nobody can be fully prepared to a pandemic. Of course there are signs of it, the scientists can predict, alarming speeches can be made. But there are always alarmist people around, maybe that is why sometimes even the most serious warnings may be not considered by the authorities on time. The first patients may be lost without a proper diagnosis. When everybody realizes that there may be a big problem in the horizon, sometimes it is too late. That is why it is very important to monitor contagious diseases and follow the warnings and releases of national and international disease control centers and other related organizations. China celebrated Lunar New Year with more than 40 thousand families on the 18 of January 2020. Nobody seem to be expecting this emerging new viral pneumonia outbreak appeared in Wuhan, in the last days of 2019, will break the chains and turn out to be a pandemic! But maybe this time it was not too late. There were four important pandemics within the last century: Spanish Flu, Hong Kong Flu, Asian Flu and Swine Flu. Each left different story behind. Millions of people had infected, hundreds, thousands of people died. This time, the Modern World had different tools to limit the SARS CoV2 outbreak. The national and international institutions of our globe were all communicating and taking precautions in a very fast manner than ever. However, this time, unexpectedly, the SARS-CoV-2 contagion was also faster. Besides the international organizations like WHO, UNESCO and UNICEF, the roles of local authorities, health ministries, disease control centers, health protection agencies, research centers and universities are all very important in different operational levels to control and survive from the pandemic. This paper will review the immediate response of different national and international institutions and authorities to COVID-19 pandemic.

negative: [Health protection guideline of mobile cabin hospitals during Novel Coronavirus Pneumonia (NPC) outbreak]. This guideline is applicable to the health protection requirements of large indoor stadiums which are reconstructed as treatment sites for the Novel Coronavirus Pneumonia (NPC) patients with mild symptoms during the outbreak. Focusing on the health emergency scenario of severe virus infectious diseases and atypical places where NPC patients with mild symptom gather, from perspectives of functional zones, hygiene facilities, personal protection, and management system, health risk protection recommendations and countermeasures are comprehensively proposed to mainly protect staffs and surrounding environment. The implementation of this guideline will provide technique support for emergency requirements of indoor stadiums reconstructed as mobile cabin hospitals.

negative: Fear of the coronavirus (COVID-19): Predictors in an online study conducted in March 2020 Fear is an adaptive response in the presence of danger. However, when threat is uncertain and continuous, as in the current coronavirus disease (COVID-19) pandemic, fear can become chronic and burdensome. To identify predictors of fear of the coronavirus, we conducted an online survey (N = 439) three days after the World Health Organization declared the coronavirus outbreak a pandemic (i.e., between March 14 and 17, 2020). Fear of the coronavirus was assessed with the newly developed Fear of the Coronavirus Questionnaire (FCQ) consisting of eight questions pertaining to different dimensions of fear (e.g., subjective worry, safety behaviors, preferential attention), and an open-ended question. The predictors included psychological vulnerability factors (i.e., intolerance of uncertainty, worry, and health anxiety), media exposure, and personal relevance (i.e., personal health, risk for loved ones, and risk control). We found four predictors for the FCQ in a simultaneous regression analysis: health anxiety, regular media use, social media use, and risks for loved ones (R(2) = .37). Furthermore, 16 different topics of concern were identified based participants’ open-ended responses, including the health of loved ones, health care systems overload, and economic consequences. We discuss the relevance of our findings for managing people’s fear of the coronavirus.

negative: Influenza Influenza is an infectious respiratory disease that, in humans, is caused by influenza A and influenza B viruses. Typically characterized by annual seasonal epidemics, sporadic pandemic outbreaks involve influenza A virus strains of zoonotic origin. The WHO estimates that annual epidemics of influenza result in ~1 billion infections, 3–5 million cases of severe illness and 300,000–500,000 deaths. The severity of pandemic influenza depends on multiple factors, including the virulence of the pandemic virus strain and the level of pre-existing immunity. The most severe influenza pandemic, in 1918, resulted in >40 million deaths worldwide. Influenza vaccines are formulated every year to match the circulating strains, as they evolve antigenically owing to antigenic drift. Nevertheless, vaccine efficacy is not optimal and is dramatically low in the case of an antigenic mismatch between the vaccine and the circulating virus strain. Antiviral agents that target the influenza virus enzyme neuraminidase have been developed for prophylaxis and therapy. However, the use of these antivirals is still limited. Emerging approaches to combat influenza include the development of universal influenza virus vaccines that provide protection against antigenically distant influenza viruses, but these vaccines need to be tested in clinical trials to ascertain their effectiveness.

negative: This Time Must Be Different: Disparities During the COVID-19 Pandemic African Americans and Latinos are overrepresented among cases of and deaths from COVID-19 nationally and in many of the U.S. regions hardest hit by the pandemic. The editorialist discusses lessons that we should have learned from prior experiences and strategies to reduce observed disparities.

negative: Plagues, pandemics and epidemics in Irish history prior to COVID-19 (coronavirus): what can we learn? OBJECTIVES: This paper seeks to provide a brief overview of epidemics and pandemics in Irish history and to identify any lessons that might be useful in relation to psychiatry in the context of COVID-19. METHODS: A review of selected key reports, papers and publications related to epidemics and pandemics in Irish history was conducted. RESULTS: Viruses, epidemics and pandemics are recurring features of human history. Early Irish sources record a broad array of plagues, pandemics and epidemics including bubonic plague, typhus, cholera, dysentery and smallpox, as well as an alleged epidemic of insanity in the 19th century (that never truly occurred). Like the Spanish flu pandemic (1918–20), COVID-19 (a new coronavirus) presents both the challenge of the illness itself and the problems caused by the anxiety that the virus triggers. Managing this anxiety has always been a challenge, especially with the Spanish flu. People with mental illness had particularly poor outcomes with the Spanish flu, often related to the large, unhygienic mental hospitals in which so many were housed. CONCLUSIONS: Even today, a full century after the Spanish flu pandemic, people with mental illness remain at increased risk of poor physical health, so it is imperative that multi-disciplinary care continues during the current outbreak of COVID-19, despite the manifest difficulties involved. The histories of previous epidemics and pandemics clearly demonstrate that good communication and solidarity matter, now more than ever, especially for people with mental illness.

negative: Metagenomic Nanopore sequencing of influenza virus direct from clinical respiratory samples Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples We generated influenza virus reads down to a limit of detection of 102 to 103 genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (P=4 7×10-5) Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [CT] values, <30) and 6/13 samples with low viral titers (CT values, 30 to 40) No false-positive reads were generated from 10 influenza virus-negative samples Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments We also detected a human coronavirus coinfection in one clinical sample While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses

negative: Epidemiological and clinical features of human coronavirus infections among different subsets of patients BACKGROUND: Epidemiological and clinical data of human coronaviruses (HCoVs) infections are restricted to span 1–3 years at most. We conducted a comprehensive 9‐year study on HCoVs by analyzing 1137 respiratory samples from four subsets of patients (asymptomatic, general community, with comorbidities, and hospitalized) in São Paulo, Brazil. METHODS: A pan‐coronavirus RT‐PCR screening assay was performed, followed by species‐specific real‐time RT‐PCR monoplex assays. RESULTS: Human coronaviruses were detected in 88 of 1137 (7.7%) of the samples. The most frequently detected HCoV species were NL63 (50.0%) and OC43 (27.3%). Patients with comorbidities presented the highest risk of acquiring coronavirus infection (odds ratio = 4.17; 95% confidence interval = 1.9–9.3), and children with heart diseases revealed a significant HCoV infection presence. Dyspnea was more associated with HCoV‐229E infections (66.6%), and cyanosis was reported only in HCoV‐OC43 infections. There were interseasonal differences in the detection frequencies, with HCoV‐229E being predominant in the year 2004 (61.5%) and HCoV‐NL63 (70.8%) in 2008. CONCLUSIONS: Our data provide a novel insight into the epidemiology and clinical knowledge of HCoVs among different subsets of patients, revealing that these viruses may cause more than mild respiratory tract disease.

negative: Effectiveness of the measures to flatten the epidemic curve of COVID-19. The case of Spain Abstract After the cases of COVID-19 skyrocketed, showing that it was no longer possible to contain the spread of the disease, the governments of many countries launched mitigation strategies, trying to slow the spread of the epidemic and flatten its curve. The Spanish Government adopted physical distancing measures on March 14; 13 days after the epidemic outbreak started its exponential growth. Our objective in this paper was to evaluate ex-ante (before the flattening of the curve) the effectiveness of the measures adopted by the Spanish Government to mitigate the COVID-19 epidemic. Our hypothesis was that the behavior of the epidemic curve is very similar in all countries. We employed a time series design, using information from January 17 to April 5, 2020 on the new daily COVID-19 cases from Spain, China and Italy. We specified two generalized linear mixed models (GLMM) with variable response from the Gaussian family (i.e. linear mixed models): one to explain the shape of the epidemic curve of accumulated cases and the other to estimate the effect of the intervention. Just one day after implementing the measures, the variation rate of accumulated cases decreased daily, on average, by 3.059 percentage points, (95% credibility interval: −5.371, −0.879). This reduction will be greater as time passes. The reduction in the variation rate of the accumulated cases, on the last day for which we have data, has reached 5.11 percentage points. The measures taken by the Spanish Government on March 14, 2020 to mitigate the epidemic curve of COVID-19 managed to flatten the curve and although they have not (yet) managed to enter the decrease phase, they are on the way to do so.

negative: Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis BACKGROUND: Since December 2019, 2019 novel coronavirus pneumonia emerged in Wuhan city and rapidly spread throughout China and even the world. We sought to analyse the clinical characteristics and laboratory findings of some cases with 2019 novel coronavirus pneumonia . METHODS: In this retrospective study, we extracted the data on 95 patients with laboratory-confirmed 2019 novel coronavirus pneumonia in Wuhan Xinzhou District People’s Hospital from January 16th to February 25th, 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until March 2th, 2020. RESULTS: Higher temperature, blood leukocyte count, neutrophil count, neutrophil percentage, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, α - hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and so were lower lymphocyte count, lymphocyte percentage and total protein level. Age below 40 or above 60 years old, male, higher Creatinine level, and lower platelet count also seemed related to severe 2019 novel coronavirus pneumonia and composite endpoint, however the P values were greater than 0.05, which mean under the same condition studies of larger samples are needed in the future. CONCLUSION: Multiple factors were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and more related studies are needed in the future.

negative: One health, multiple challenges: The inter-species transmission of influenza A virus Influenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Influenza A viruses are unique in many ways. Firstly, they are unique in the diversity of host species that they infect. This includes waterfowl (the original reservoir), terrestrial and aquatic poultry, swine, humans, horses, dog, cats, whales, seals and several other mammalian species. Secondly, they are unique in their capacity to evolve and adapt, following crossing the species barrier, in order to replicate and spread to other individuals within the new species. Finally, they are unique in the frequency of inter-species transmission events that occur. Indeed, the consequences of novel influenza virus strain in an immunologically naïve population can be devastating. The problems that influenza A viruses present for human and animal health are numerous. For example, influenza A viruses in humans represent a major economic and disease burden, whilst the poultry industry has suffered colossal damage due to repeated outbreaks of highly pathogenic avian influenza viruses. This review aims to provide a comprehensive overview of influenza A viruses by shedding light on interspecies virus transmission and summarising the current knowledge regarding how influenza viruses can adapt to a new host.

negative: A Systematic Review Analyzing the Prevalence and Circulation of Influenza Viruses in Swine Population Worldwide The global anxiety and a significant threat to public health due to the current COVID-19 pandemic reiterate the need for active surveillance for the zoonotic virus diseases of pandemic potential. Influenza virus due to its wide host range and zoonotic potential poses such a significant threat to public health. Swine serve as a “mixing vessel” for influenza virus reassortment and evolution which as a result may facilitate the emergence of new strains or subtypes of zoonotic potential. In this context, the currently available scientific data hold a high significance to unravel influenza virus epidemiology and evolution. With this objective, the current systematic review summarizes the original research articles and case reports of all the four types of influenza viruses reported in swine populations worldwide. A total of 281 articles were found eligible through screening of PubMed and Google Scholar databases and hence were included in this systematic review. The highest number of research articles (n = 107) were reported from Asia, followed by Americas (n = 97), Europe (n = 55), Africa (n = 18), and Australia (n = 4). The H1N1, H1N2, H3N2, and A(H1N1)pdm09 viruses were the most common influenza A virus subtypes reported in swine in most countries across the globe, however, few strains of influenza B, C, and D viruses were also reported in certain countries. Multiple reports of the avian influenza virus strains documented in the last two decades in swine in China, the United States, Canada, South Korea, Nigeria, and Egypt provided the evidence of interspecies transmission of influenza viruses from birds to swine. Inter-species transmission of equine influenza virus H3N8 from horse to swine in China expanded the genetic diversity of swine influenza viruses. Additionally, numerous reports of the double and triple-reassortant strains which emerged due to reassortments among avian, human, and swine strains within swine further increased the genetic diversity of swine influenza viruses. These findings are alarming hence active surveillance should be in place to prevent future influenza pandemics.

negative: Sequence comparison of porcine respiratory coronavirus isolates reveals heterogeneity in the S, 3, and 3-1 genes. Four new porcine respiratory coronavirus (PRCV) isolates were genetically characterized. Subgenomic mRNA patterns and the nucleotide sequences of the 5' ends of the S genes, the open reading frame (ORF) 3/3a genes, and the ORF 3-1/3b genes of these PRCV isolates were determined and compared with those of other PRCV and transmissible gastroenteritis virus (TGEV) isolates. The S, ORF 3/3a, and ORF 3-1/3b genes are under intense study because of their possible roles in determining tissue tropism and virulence. Northern (RNA) blot analysis of subgenomic mRNAs revealed that mRNA 2, which encodes for the S gene, of the PRCV isolates migrated faster than the mRNA 2 of TGEV. The PRCV isolates AR310 and LEPP produced eight subgenomic mRNA species, the same number as produced by the virulent Miller strain of TGEV. However, the PRCV isolates IA1894 and ISU-1 produced only seven subgenomic mRNA species. All four of the PRCV isolates were found to have a large in-frame deletion in the 5' end of the S gene; however, the size and location of the deletion varied. Analysis of the ORF 3/3a gene nucleotide sequences from the four PRCV isolates also showed a high degree of variability in this area. The ORF 3 gene of the PRCV isolates AR310 and LEPP was preceded by a CTAAAC leader RNA-binding site, and the ORF 3 gene was predicted to yield a protein of 72 amino acids, the same size as that of the virulent Miller strain of TGEV. The PRCV isolates AR310 and LEPP are the first PRCV isolates found to have an intact ORF 3 gene. The ORF 3a gene of the PRCV isolate IA1894 was preceded by a CTAAAC leader RNA-binding site and was predicted to yield a truncated protein of 54 amino acids due to a 23-nucleotide deletion. The CTAAAC leader RNA-binding site and ATG start codon of ORF 3 gene of the PRCV isolate ISU-1 were removed because of a 168-nucleotide deletion. Analysis of the ORF 3-1/3b gene nucleotide sequences from the four PRCV nucleotides isolates also showed variability.

negative: Utility of Substandard Face Mask Options for Health Care Workers During the COVID-19 Pandemic

negative: Influence of interferon-based drugs on immunological indices in specific prevention AIM: The research aimed to study the effect of interferon (IFN)-based drugs on the behavior of immunological parameters in calves during the specific prevention of associative infections. MATERIALS AND METHODS: The object of research was 45 black motley cows and their calves from birth to 2 months of life. Serum and colostrum samples were screened for antibodies against Rotavirus, diarrhea, and coronavirus using serological methods. The testing was performed before vaccination, 40 days before calving, 20 days before calving, and before calving. Colostrum samples were taken during the first milk yield. Serum samples from calves were drawn before colostrum feeding as well as at 7, 14, and 21 days, and 1 and 2 months of age. To measure the level of immunoglobulins A, M, and G, additional serum samples were collected from calves at 25, 35, 65, and 75 days after birth. RESULTS: Giving pregnant cows, an IFN-based drug at a dose of 1 ml/kg 48 h before vaccination results in the development and accumulation of antibodies to Rotavirus, coronavirus, and viral diarrhea (VD) in the colostrum, with a titer of 7.6±0.3 log(2), 5.8±0.34 log(2), and 4.4±0.18 log(2), respectively. It indicates an increase in the antigenic activity of the multivalent vaccine. CONCLUSION: IFN-based drugs enhance the protective effect of vaccination against associative infections in the newborn calves. They stimulate a rise in the titer of antibodies to Rotavirus, coronavirus, VD, and mucosal disease complex as well as an increase in immunoglobulins A, M, and G.

negative: Influenza A☆ Abstract The influenza viruses, which contain single-stranded RNA, are classified into three types, A, B, and C and belong to the Orthomyxoviridae family of viruses. Types A and B cause annual epidemics and often pandemics of influenza illness, while type C is a less common disease with fewer symptoms.

negative: Evidence that higher temperatures are associated with lower incidence of COVID-19 in pandemic state, cumulative cases reported up to March 27, 2020 Seasonal temperature variation may impact the trajectories of COVID-19 in different global regions. Cumulative data reported by the World Health Organization, for dates up to March 27, 20201, show association between COVID-19 incidence and regions at or above 30° latitude. Historic climate data also show significant reduction of case rates with mean maximum temperature above approximately 22.5 degrees Celsius. Variance at the local level, however, could not be well explained by geography and temperature. These preliminary findings support continued countermeasures and study of SARS-CoV-2/COVID-19 transmission rates by temperature and humidity.

negative: Evaluating the diagnostic accuracy of the WHO Severe Acute Respiratory Infection (SARI) criteria in Middle Eastern children under two years over three respiratory seasons OBJECTIVE: The World Health Organization created the Severe Acute Respiratory Infection (SARI) criteria in 2011 to monitor influenza (flu)-related hospitalization. Many studies have since used the SARI case definition as inclusion criteria for surveillance studies. We sought to determine the sensitivity, specificity, positive predictive value, and negative predictive value of the SARI criteria for detecting ten different respiratory viruses in a Middle Eastern pediatric cohort. MATERIALS AND METHODS: The data for this study comes from a prospective acute respiratory surveillance study of hospitalized children <2 years in Amman, Jordan from March 16, 2010 to March 31, 2013. Participants were recruited if they had a fever and/or respiratory symptoms. Nasal and throat swabs were obtained and tested by real-time RT-PCR for eleven viruses. Subjects meeting SARI criteria were determined post-hoc. Sensitivity, specificity, positive predictive value, and negative predictive value of the SARI case definition for detecting ten different viruses were calculated and results were stratified by age. RESULTS: Of the 3,175 patients enrolled, 3,164 were eligible for this study, with a median age of 3.5 months, 60.4% male, and 82% virus-positive (44% RSV and 3.8% flu). The sensitivity and specificity of the SARI criteria for detecting virus-positive patients were 44% and 77.9%, respectively. Sensitivity of SARI criteria for any virus was lowest in children <3 months at 22.4%. Removing fever as a criterion improved the sensitivity by 65.3% for detecting RSV in children <3 months; whereas when cough was removed, the sensitivity improved by 45.5% for detecting flu in same age group. CONCLUSIONS: The SARI criteria have poor sensitivity for detecting RSV, flu, and other respiratory viruses—particularly in children <3 months. Researchers and policy makers should use caution if using the criteria to estimate burden of disease in children.

negative: Dataset on dynamics of Coronavirus on Twitter Abstract In this data article, we provide a dataset of 8,982,694 Twitter posts around the coronavirus health global crisis. The data were collected through the Twitter REST API search. We used the rtweet R package to download raw data. The term searched was “Coronavirus” which included the word itself and its hashtag version. We collected the data over 23 days, from January 21 to February 12, 2020. The dataset is multilingual, prevailing English, Spanish, and Portuguese. We include a new variable created from other four variables; it is called “type” of tweets, which is useful for showing the diversity of tweets and the dynamics of users on Twitter. The dataset comprises seven databases which can be analysed separately. On the other hand, they can be crossed to set other researches, among them, trends and relevance of different topics, types of tweets, the embeddedness of users and their profiles, the retweets dynamics, hashtag analysis, as well as to perform social network analysis. This dataset can attract the attention of researchers related to different fields on knowledge, such as data science, social science, network science, health informatics, tourism, infodemiology, and others.

negative: Binding of SARS-CoV-2 and angiotensin-converting enzyme 2: clinical implications

negative: How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1 SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation "breaks down" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.

negative: Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. Four human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory outcomes, including bronchiolitis and pneumonia. Their epidemiologies and clinical characteristics are poorly described and are often reliant on case reports. To address these problems, we conducted a large-scale comprehensive screening for all four coronaviruses by analysis of 11,661 diagnostic respiratory samples collected in Edinburgh, United Kingdom, over 3 years between July 2006 and June 2009 using a novel four-way multiplex real-time reverse transcription-PCR (RT-PCR) assay. Coronaviruses were detected in 0.3 to 0.85% of samples in all age groups. Generally, coronaviruses displayed marked winter seasonality between the months of December and April and were not detected in summer months, which is comparable to the pattern seen with influenza viruses. HCoV-229E was the exception; detection was confined to the winter of 2008 and was sporadic in the following year. There were additional longer-term differences in detection frequencies between seasons, with HCoV-OC43 predominant in the first and third seasons and HCoV-HKU1 dominating in the second (see Results for definitions of seasons). A total of 11 to 41% of coronaviruses detected were in samples testing positive for other respiratory viruses, although clinical presentations of coronavirus monoinfections were comparable to those of viruses which have an established role in respiratory disease, such as respiratory syncytial virus, influenza virus, and parainfluenza viruses. The novel multiplex assay for real-time pan-coronavirus detection enhances respiratory virus diagnosis, overcomes potential diagnostic problems arising through seasonal variation in coronavirus frequency, and provides novel insights into the epidemiology and clinical implications of coronaviruses.

negative: Comparison of Different Kits for SARS-CoV-2 RNA Extraction Marketed in Brazil December 2019 marked the begining of the greatest pandemic since Spanish Flu, the disease named Covid-19 that cause severe pneumonia. Until May 19, 2020 more than 4 million and 700 thousand cases were oficially notified with about 316 thousand deaths. Etiological agent of the disease was identified as being a new coronavirus, Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). In this study we compared four different manual methods for RNA isolation and purification for detection of SARS-CoV-2 through qRT-PCR, as well as the extraction quality itself through detection of RNAse P. Magnetic beads-based (MagMax™) and silica column-based (Biopur®) methods presented the better performances. Concerning to the mean delay in CT values when compared to MagMax™, TRIzol™, Biopur® and EasyExtract presented 0,39, 0,95 and 5,23 respectively. Agreement between positive and negative results of different methods when compared with the one with better performance MagMax™ was 94,44% for silica column-based method (Biopur®), 88,89% for phenol-chroloform-based method (TRIzol™) and 77,78% for EasyExtract. We aimed to evaluate how reliable each method is for diagnostic purposes and to propose alternatives when usual methods are not available. In this regard, magnectic beads and silica column-based methods are convenient and reliable choices and phenol-chloroform-based method could also be chosen as an alternative.

negative: Voice from China: nomenclature of the novel coronavirus and related diseases

negative: Viral infections in outpatients with medically attended acute respiratory illness during the 2012–2013 influenza season BACKGROUND: While it is known that acute respiratory illness (ARI) is caused by an array of viruses, less is known about co-detections and the resultant comparative symptoms and illness burden. This study examined the co-detections, the distribution of viruses, symptoms, and illness burden associated with ARI between December 2012 and March 2013. METHODS: Outpatients with ARI were assayed for presence of 18 viruses using multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) to simultaneously detect multiple viruses. RESULTS: Among 935 patients, 60% tested positive for a single virus, 9% tested positive for ≥1 virus and 287 (31%) tested negative. Among children (<18 years), the respective distributions were 63%, 14%, and 23%; whereas for younger adults (18–49 years), the distributions were 58%, 8%, and 34% and for older adults (≥50 years) the distributions were 61%, 5%, and 32% (P < 0.001). Co-detections were more common in children than older adults (P = 0.01), and less frequent in households without children (P = 0.003). Most frequently co-detected viruses were coronavirus, respiratory syncytial virus, and influenza A virus. Compared with single viral infections, those with co-detections less frequently reported sore throat (P = 0.01), missed fewer days of school (1.1 vs. 2 days; P = 0.04), or work (2 vs. 3 days; P = 0.03); other measures of illness severity did not vary. CONCLUSIONS: Among outpatients with ARI, 69% of visits were associated with a viral etiology. Co-detections of specific clusters of viruses were observed in 9% of ARI cases particularly in children, were less frequent in households without children, and were less symptomatic (e.g., lower fever) than single infections.

negative: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare and respond to COVID‐19 The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID‐19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time‐based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short‐ and long‐term interventions to manage outbreaks at the international, national and sub‐national levels in the region. This article is protected by copyright. All rights reserved.

negative: Viral etiologies and epidemiology of patients with acute respiratory infections based on sentinel hospitals in Gansu Province, Northwest China, 2011‐2015 Understanding etiological role and epidemiological profile is needed to improve clinical management and prevention of acute respiratory infections (ARIs). A 5‐year prospective study about active surveillance for outpatients and inpatients with ARIs was conducted in Gansu province, China, from January 2011 to November 2015. Respiratory specimens were collected from patients and tested for eight respiratory viruses using polymerase chain reaction (PCR) or reverse transcription polymerase chain reaction (RT‐PCR). In this study, 2768 eligible patients with median age of 43 years were enrolled including pneumonia (1368, 49.2%), bronchitis (435, 15.7%), upper respiratory tract infection or URTI (250, 9.0%), and unclassified ARI (715, 25.8%). Overall, 29.2% (808/2768) were positive for any one of eight viruses, of whom 130 cases were identified with two or more viruses. Human rhinovirus (HRV) showed the highest detection rate (8.6%), followed by influenza virus (Flu, 7.3%), respiratory syncytial virus (RSV, 6.1%), human coronavirus (hCoV, 4.3%), human parainfluenza (PIV, 4.0%), adenovirus (ADV, 2.1%), human metapneumovirus (hMPV, 1.6%), and human bocavirus (hBoV, 0.7%). Compared with URTI, RSV was more likely identified in pneumonia (χ(2) = 12.720, P < 0.001) and hCoV was more commonly associated with bronchitis than pneumonia (χ(2) = 15.019, P < 0.001). In patients aged less than 5 years, RSV showed the highest detection rate and hCoV was the most frequent virus detected in adults and elderly. The clear epidemical seasons were observed in HRV, Flu, and hCoV infections. These findings could serve as a reference for local health authorities in drawing up further plans to prevent and control ARIs associated with viral etiologies.

negative: Viral etiology of influenza‐like illnesses during the influenza season between December 2011 and April 2012 The aim of this study was to determine the frequency of respiratory viruses responsible for respiratory tract infections in Turkish children during the 2011–2012 influenza season. Nasal swabs were obtained from patients with symptoms suggestive of an influenza‐like illness between December 2011 and April 2012. Samples were analyzed with multiplex real‐time polymerase chain reaction (RT‐PCR) to help identify the causative viral pathogen. A total of 200 patients were enrolled in the study. A respiratory virus was detected successfully in 102 (51%) children; influenza A (H3N2) in 39.2%, influenza B in 23.5%, RSV in 15.6%, rhinovirus in 13.7%, bocavirus in 2.9%, coronavirus in 2.9%, and metapneumovirus in 0.9% of patients. Only one patient was co‐infected with bocavirus and influenza A virus. A statistically significant difference in the mean age of presentation was observed between the various viral pathogens (P < 0.001). Patients with RSV were significantly younger whereas children infected with the influenza viruses were significantly older. Comparison of symptoms revealed that fever and headache occurred more frequently with the influenza viruses than the other viruses combined (P < 0.001, <0.05). Durations of symptoms such as fever, cough, nasal congestion, and rhinorrhea were also significantly longer in the influenza group (P < 0.001, <0.005, <0.001, <0.005, respectively). Demographic analyses revealed that the school/daycare attendance was the only parameter associated with a significantly increased risk for influenza infection. With an overall viral pathogen detection rate of 51%, findings of the present study suggest other respiratory pathogens, whether viral or bacterial, may also lead to hospital visits due to influenza‐like illnesses in children. J. Med. Virol. 86:865–871, 2014. © 2013 Wiley Periodicals, Inc.

negative: Planning for avian influenza. Avian influenza, or influenza A (H5N1), has 3 of the 4 properties necessary to cause a serious pandemic: It can infect people, nearly all people are immunologically naive, and it is highly lethal. The Achilles heel of the virus is the lack of sustained human-human transmission. Fortunately, among the 124 cases reported through 30 May 2006, nearly all were acquired by direct contact with poultry. Unfortunately, the capability for efficient human-human transmission requires only a single mutation by a virus that is notoriously genetically unstable, hence the need for a new vaccine each year for seasonal influenza. Influenza A (H5N1) is being compared to another avian strain, the agent of the "Spanish flu" of 1918-1919, which traversed the world in 3 months and caused an estimated 50 million deaths. The question is, are we ready for this type of pandemic? The answer is probably no. The main problems are the lack of an effective vaccine, very poor surge capacity, a health care system that could not accommodate even a modest pandemic, and erratic regional planning. It's time to get ready, and in the process be ready for bioterrorism, natural disasters, and epidemics of other infectious diseases.

negative: Dr. Wu Lien Teh, plague fighter and father of the Chinese public health system

negative: Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.

negative: Brief review of coronavirus for healthcare professionals February 10, 2020 A novel epidemic is challenging the global health care system Starting from probably November to December 2019, another Coronavirus entered the arena of human pathogens, to be then defined 2019- nCoV [ ]

negative: Abdominal Pain: A Real Challenge in Novel COVID-19 Infection COVID-19 (coronavirus disease 19) is an infectious disease caused by coronavirus 2019-nCoV. Since its detection in China at the end of 2019, the novel coronavirus has rapidly spread throughout the world and has caused an international public health emergency. The most common manifestation is flu-like symptoms. Mild infections usually improve within a few days, but COVID-19 can cause severe pneumonia with acute respiratory distress syndrome and death. Gastrointestinal symptoms are less common but possible and more difficult to recognize as part of a COVID-19 syndrome. In line with the current opinion of the WHO, we strongly believe that preventive measures and early diagnosis of COVID-19 are crucial to interrupt virus spread and avoid local outbreaks. We report the cases of COVID-19 patients admitted to our Emergency Department who complained of gastrointestinal symptoms at admission. LEARNING POINTS: The novel COVID-19 infection is a severe public health problem which is causing an increasing number of deaths worldwide. Although uncommon, there may be a relationship between gastrointestinal symptoms and COVID-19, as reported in recent studies. Early detection and isolation of patients with COVID-19 infection is the only way to control and limit the global spread of this virus.

negative: Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.

negative: Recognizing flu-like symptoms from videos BACKGROUND: Vision-based surveillance and monitoring is a potential alternative for early detection of respiratory disease outbreaks in urban areas complementing molecular diagnostics and hospital and doctor visit-based alert systems. Visible actions representing typical flu-like symptoms include sneeze and cough that are associated with changing patterns of hand to head distances, among others. The technical difficulties lie in the high complexity and large variation of those actions as well as numerous similar background actions such as scratching head, cell phone use, eating, drinking and so on. RESULTS: In this paper, we make a first attempt at the challenging problem of recognizing flu-like symptoms from videos. Since there was no related dataset available, we created a new public health dataset for action recognition that includes two major flu-like symptom related actions (sneeze and cough) and a number of background actions. We also developed a suitable novel algorithm by introducing two types of Action Matching Kernels, where both types aim to integrate two aspects of local features, namely the space-time layout and the Bag-of-Words representations. In particular, we show that the Pyramid Match Kernel and Spatial Pyramid Matching are both special cases of our proposed kernels. Besides experimenting on standard testbed, the proposed algorithm is evaluated also on the new sneeze and cough set. Empirically, we observe that our approach achieves competitive performance compared to the state-of-the-arts, while recognition on the new public health dataset is shown to be a non-trivial task even with simple single person unobstructed view. CONCLUSIONS: Our sneeze and cough video dataset and newly developed action recognition algorithm is the first of its kind and aims to kick-start the field of action recognition of flu-like symptoms from videos. It will be challenging but necessary in future developments to consider more complex real-life scenario of detecting these actions simultaneously from multiple persons in possibly crowded environments.

negative: Novel Virus Influenza A (H1N1sw) in South-Eastern France, April-August 2009 BACKGROUND: In April 2009, the first cases of pandemic (H1N1)-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones. METHODOLOGY/PRINCIPAL FINDINGS: We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i) Nasal swabs were tested using rapid influenza diagnostic test (RIDT) and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus) and distribution in age groups and results of RIDT were analyzed. (ii) 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii) One early (May 2009) and one late (July 2009) viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii) Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed. CONCLUSIONS/SIGNIFICANCE: This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1)-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in children, especially in the context of the investigation of grouped cases.

negative: Pandemic influenza: mass gatherings and mass infection

negative: Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data BACKGROUND: Infectious disease surveillance is a process the product of which reflects both actual disease trends and public awareness of the disease. Decisions made by patients, health care providers, and public health professionals about seeking and providing health care and about reporting cases to health authorities are all influenced by the information environment, which changes constantly. Biases are therefore imbedded in surveillance systems; these biases need to be characterized to provide better situational awareness for decision-making purposes. Our goal is to develop a statistical framework to characterize influenza surveillance systems, particularly their correlation with the information environment. METHODS: We identified Hong Kong influenza surveillance data systems covering healthcare providers, laboratories, daycare centers and residential care homes for the elderly. A Bayesian hierarchical statistical model was developed to examine the statistical relationships between the influenza surveillance data and the information environment represented by alerts from HealthMap and web queries from Google. Different models were fitted for non-pandemic and pandemic periods and model goodness-of-fit was assessed using common model selection procedures. RESULTS: Some surveillance systems — especially ad hoc systems developed in response to the pandemic flu outbreak — are more correlated with the information environment than others. General practitioner (percentage of influenza-like-illness related patient visits among all patient visits) and laboratory (percentage of specimen tested positive) seem to proportionally reflect the actual disease trends and are less representative of the information environment. Surveillance systems using influenza-specific code for reporting tend to reflect biases of both healthcare seekers and providers. CONCLUSIONS: This study shows certain influenza surveillance systems are less correlated with the information environment than others, and therefore, might represent more reliable indicators of disease activity in future outbreaks. Although the patterns identified in this study might change in future outbreaks, the potential susceptibility of surveillance data is likely to persist in the future, and should be considered when interpreting surveillance data. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-850) contains supplementary material, which is available to authorized users.

negative: [Seasonal patterns of coronavirus infections in Hamburg]. During a serological surveillance programme between October 1974 and September 1975 in Hamburg, 1624 sera from all age groups of the population were examined for the presence of coronavirus antibodies (OC 43 agent). 61,51% of the sera showed HI-titres between 1:8 and 1:128. The geometric mean antiboty titre (GMT) for the whole group was 1:12,2. The serological seasonal pattern suggests that coronaviruses are circulating the whole year in the urban population with a prevalence in the cold and a decrease in the warm season (June). The highest incidence of seropositive reactions (82,9%) was found in the 15-24 years old individuals (GMT 1:13,8). These data indicate an increased spread of coronaviruses in this segment of the population and a marked susceptibility of the group.

negative: SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.

negative: COVID-19 Pandemic and Impending Global Mental Health Implications. The increase in organisms transference and infectious pandemics across the globe have been accelerated by an increase in travel, international exchange and global changes in earth's climate. COVID-19, a virus caused by the novel coronavirus that was initially identified on December 2019, in Wuhan city of China is currently affecting 146 territories, states and countries raising distress, panic and increasing anxiety in individuals exposed to the (actual or supposed) peril of the virus across the globe. Fundamentally, these concerns ascend with all infections, including those of flu and other agents, and the same worldwide safeguards are compulsory and suggested for protection and the prevention of further diffusion. However, media has underlined COVID-19 as rather an exclusive threat, which has added to panic and stress in masses which can lead to several mental health issues like anxiety, obsessive compulsive disorder and post-traumatic stress disorder which should be contained immediately in its initial phases.

negative: Current Approaches for Diagnosis of Influenza Virus Infections in Humans Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans.

negative: Viruses with Single-Stranded, Positive-Sense RNA Genomes Eight virus families whose members infect vertebrates are currently known to possess single-stranded, positive-sense RNA genomes: the families Picornaviridae, Caliciviridae and Hepeviridae have non-enveloped capsids, whereas the families Flaviviridae, Togaviridae, Arteriviridae and Coronaviridae are characterized by enveloped capsids. They all have in common the property of using their own genome as messenger RNA (mRNA), from which they synthesize one or several polyproteins that are subsequently cleaved into individual proteins by viral or cellular proteases. These viruses possess the genetic information for the synthesis of an RNA-dependent RNA polymerase. This enzyme transcribes the positive RNA strand as well as the complementary negative RNA strands, which arise as intermediate products of genome replication. In the course of this process, the new genomic RNA molecules are generated from the second transcription step. The classification into the different taxonomic families depends on the number, size, position and orientation of viral genes in the RNA molecule, the number of different polyproteins that are synthesized during viral infection and the existence of an envelope as a virion component.

negative: Prospective Evaluation for Respiratory Pathogens in Children With Sickle Cell Disease and Acute Respiratory Illness BACKGROUND: Human rhinovirus (HRV), human coronavirus (hCoV), human bocavirus (hBoV), and human metapneumovirus (hMPV) infections in children with sickle cell disease have not been well studied. PROCEDURE: Nasopharyngeal wash specimens were prospectively collected from 60 children with sickle cell disease and acute respiratory illness, over a 1-year period. Samples were tested with multiplexed-PCR, using an automated system for nine respiratory viruses, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Bordetella pertussis. Clinical characteristics and distribution of respiratory viruses in patients with and without acute chest syndrome (ACS) were evaluated. RESULTS: A respiratory virus was detected in 47 (78%) patients. Nine (15%) patients had ACS; a respiratory virus was detected in all of them. The demographic characteristics of patients with and without ACS were similar. HRV was the most common virus, detected in 29 of 47 (62%) patients. Logistic regression showed no association between ACS and detection of HRV, hCoV, hBoV, hMPV, and other respiratory pathogens. Co-infection with at least one additional respiratory virus was seen in 14 (30%) infected patients, and was not significantly higher in patients with ACS (P=0.10). Co-infections with more than two respiratory viruses were seen in seven patients, all in patients without ACS. Bacterial pathogens were not detected. CONCLUSION: HRV was the most common virus detected in children with sickle cell disease and acute respiratory illness, and was not associated with increased morbidity. Larger prospective studies with asymptomatic controls are needed to study the association of these emerging respiratory viruses with ACS in children with sickle cell disease.

negative: COVID-19: how to make between-country comparisons BACKGROUND: Different countries have adopted different containment and testing strategies for SARS-CoV-2. The difference in testing makes it difficult to compare the effect of different containment strategies. We propose methods to allow a direct comparison and we present the results of this comparison. DESIGN: Publicly available data on numbers of reported COVID-19 related deaths between January 1(st) and April 17(th) 2020 were compared between countries. RESULTS: The numbers of cases or deaths per 100,000 inhabitants give severely biased comparisons between countries. Only the number of deaths expressed as a percentage of the number of deaths on day 25 after the first reported COVID-19 related death allows a direct comparison between countries. From this comparison we observed clear differences between countries, associated with the timing of the implementation of containment measures. CONCLUSIONS: Comparisons between countries are only possible when simultaneously taking into account that the virus did not arrive in all countries simultaneously, absolute numbers are incomparable due to different population sizes, rates per 100,000 of the population are incomparable because not all countries are affected homogeneously, susceptibility to death by COVID-19 can differ between populations, and a death will only be reported as a COVID-19 related death if the patient was diagnosed with SARS-CoV-2 infection. With our methods, we accounted for all these factors and established an unbiased direct comparison between countries. This comparison confirms that early adoption of containment strategies is key in flattening the curve of the epidemic.

negative: Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19

negative: Scientific Opinion on an update on the present knowledge on the occurrence and control of foodborne viruses A review of the biology, epidemiology, diagnosis and public health importance of foodborne viruses was performed. Data needs to support a risk assessment were also identified. In addition possible control options and their anticipated impact to prevent or reduce the number of foodborne viral human infections were identified, including the scientific reasons for and against the establishment of food safety criteria and process hygiene criteria for viruses for certain food categories. Food may be contaminated by virus during all stages of the food supply chain, and transmission can occur by consumption of food contaminated during the production process (primary production, or during further processing), or contaminated by infected food handlers. Transmission of zoonotic viruses (e.g. HEV) can also occur by consumption of products of animal origin. Viruses do not multiply in foods, but may persist for extended periods of time as infectious particles in the environment, or in foods. At the EU‐level it is unknown how much viral disease can be attributed to foodborne spread. The relative contribution of different sources (shellfish, fresh produce, food handler including asymptomatic shedders, food handling environment) to foodborne illness has not been determined. The Panel recommends focusing controls on preventive measures to avoid viral contamination rather than trying to remove/inactivate these viruses from food. Also, it is recommended to introduce a microbiological criteria for viruses in bivalve molluscs, unless they are labelled “to be cooked before consumption”. The criteria could be used by food business operators to validate their control options. Furthermore, it is recommended to refine the regulatory standards and monitoring approaches in order to improve public health protection. Introduction of virus microbiological criteria for classification of bivalve molluscs production areas should be considered. A virus monitoring programme for compliance with these criteria should be risk based according to the findings of a sanitary survey.

negative: Partial comparison of the NxTAG Respiratory Pathogen Panel Assay with the Luminex xTAG Respiratory Panel Fast Assay V2 and singleplex real-time polymerase chain reaction for detection of respiratory pathogens Abstract In this study, 185 nasopharyngeal swabs were tested to compare the sensitivity and specificity of the Luminex NxTAG (NxTAG) Respiratory Pathogen Panel (RPP) Assay with those of the Luminex Respiratory Virus Panel (RVP) Fast Assay v2 and singleplex real-time polymerase chain reaction (PCR). The NxTAG Assay identified at least one infectious agent in 164 (88.7%) of the swabs. In 91 (6.2%) tests with negative results with the RVP Fast Assay v2, a virus was identified by the NxTAG (P < 0.001). With the NxTAG Assay, the detection rates were significantly higher for respiratory syncytial virus (P = 0.003), human metapneumovirus (P < 0.001), human rhinovirus/human enterovirus (P = 0.009) and human adenovirus (P < 0.001). Finally, the NxTAG Assay identified M. pneumoniae in 32 of 44 (72.7%) PCR-positive samples. However, the concordance with real-time PCR results was low for both assays. In conclusion, the results indicate that the NxTAG Assay overcomes some of the limitations of previous Luminex assays, although further studies are needed for a more complete evaluation of the new assay.

negative: UK newspapers' representations of the 2009–10 outbreak of swine flu: one health scare not over-hyped by the media? BACKGROUND: A/H1N1, more commonly referred to as swine flu, emerged in Mexico in spring 2009. It rapidly spread across the world and was classed as a global pandemic on 11 June 2009. OBJECTIVE: To analyse UK newsprint coverage of the swine flu pandemic. METHODS: Content analysis of 2374 newsprint articles published in eight UK national newspapers between 1 March 2009 and 28 February 2010. RESULTS: Newsprint coverage of the swine flu epidemic was immense. The threat from swine flu was portrayed as greatest in the spring and summer of 2009 when scientific uncertainties about the impact on the UK and global population were at their height and when swine flu cases in the UK first peaked. Thereafter the number of news articles waned, failing to mirror the October peak in flu cases as the virus failed to be as virulent as first feared. Content analysis found little evidence of the media ‘over-hyping’ the swine flu pandemic. CONCLUSIONS: The news media's role as a disseminator of scientific information is particularly important in areas of risk perception. Despite a succession of health scares in recent years in which the media has been accused of exaggerating the risks and contributing to public misunderstandings of the issues, this analysis suggests that the UK newsprint reporting of swine flu in the 2009–10 outbreak was largely measured. The news media's role as disseminators of factual health information on swine flu is to be welcomed, particularly in relation to their handling and responsible reporting on scientific uncertainty.

negative: Avian influenza aided readiness for swine flu Despite gains from threat of bird flu, pandemic preparedness is patchy.

negative: Creating a comprehensive multi-tiered influenza management plan for a large healthcare system ISSUE: Influenza infections affect 20% of the U.S. population, with an average of 110,000 hospitalizations and 36,000 deaths annually. The shortage of influenza vaccine for the 2004–2005 season brought with it the potential for an even higher rate of morbidity and mortality due to influenza. The Infection Control and Healthcare Epidemiology Consortium of a 12-hospital healthcare system located in St. Louis, Missouri, determined that a comprehensive multi-tiered influenza management plan was needed. PROJECT: A team of four infection control practitioners (ICPs) was established from three of the system's hospitals, including a large, metropolitan teaching hospital, a comprehensive pediatric hospital, and a small community hospital, along with three system-level consultants, under the advisement of their medical directors. The team developed a resource packet containing a comprehensive multi-tiered influenza management plan. The packet included a core policy, to be customized by each entity, a checklist of recommended materials to have on hand, and algorithms for influenza testing, patient placement, and healthcare worker immunization. The packet also included an admission screening tool, examples of local health department' line list reports, and educational posters to be used throughout the healthcare facilities to heighten influenza infection prevention awareness. Many of the tools have specific recommendations for different stages of the influenza season; for example, extensive use of rapid diagnostic tests is appropriate early on, but unnecessary during peak flu season when diagnosis can reliably be made based on symptoms. The packet was developed as a guide to assist ICPs in preparing for an influenza season. RESULTS: A resource packet with a comprehensive multi-tiered influenza management plan was developed for all of the system's hospitals. The packet contains information addressing the action to be taken prior to and at the early onset of the influenza season, when there is an increased level of influenza activity, and during a pandemic event. LESSONS LEARNED: Annual influenza outbreaks are a serious threat to U.S. patients. To reduce that threat, it is necessary to carefully plan and prepare for each influenza season. A resource packet with a comprehensive multi-tiered influenza management plan is a useful tool in making the necessary plans and preparations.

negative: Clinical trials: management of investigational products during the coronavirus (COVID-19) pandemic Disclaimer: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

negative: Common Respiratory Tract Infections as Psychological Entities: A Review of the Mood and Performance Effects of Being Ill The clinical manifestations associated with colds and influenza overshadow the equally important mood and performance impairments. While decreased alertness and increased anxiety can be considered side effects of symptomatology, symptoms alone may not be responsible for the psychomotor and attention deficits of colds and influenza, respectively. An alternative hypothesis, as proposed in this review, suggests that the immune response, in the form of a cytokine cascade, may be responsible for both the physical and psychological symptoms. In particular, patterns of cytokine production for each infection will dictate the symptoms and performance deficits both within and between viruses. This hypothesis can be extended to incorporate infectious mononucleosis, as well as colds and influenza. The efficacy of symptom‐based overthe‐counter medications is then called into question.

negative: Recent apprise on coronavirus and its terrible insinuations Epidemically increased evidence reveals that the link between the 2019-nCoV and other similar strain of coronaviruses circulating in bats and specifically the Rhinopodous bat sub-species. These sub-species are ample and widely present in Southern China, Middle East Africa and Europe. Recent studies show that more than 500 CoV have been identified in bats in China. The Center for Diseases Control and Prevention and the World Health Organization maintains a website that is updated frequently with new cases of MERS-CoV infection. As per WHO Situation report 16th, 24,554 number of cases confirmed globally out of which 99.22% cases from china. A new coronavirus (2019-nCoV) is causing respiratory syndrome mostly in Hubei Province, China. Corona Virus spread over 24 countries including Japan, India, Korea, and other countries 2019-CoV infection vary from mild, moderate or severe illness; the later includes severe pneumonia, ARDS, sepsis and septic shock. There are two diagnostic tests for coronavirus infection i.e. molecular test and serology test. In this review article there are the various recent cases of the patients that are suffering from the corona virus, the outcome of these studies is that corona virus infection is an epidemic disease which affects Central Nervous System (CNS).

negative: Advances in respiratory virus therapeutics – A meeting report from the 6th isirv Antiviral Group conference Abstract The International Society for Influenza and other Respiratory Virus Diseases held its 6th Antiviral Group (isirv-AVG) conference in Rockville, Maryland, November 13–15, 2018. The three-day program was focused on therapeutics towards seasonal and pandemic influenza, respiratory syncytial virus, coronaviruses including MERS-CoV and SARS-CoV, human rhinovirus, and other respiratory viruses. Updates were presented on several influenza antivirals including baloxavir, CC-42344, VIS410, immunoglobulin, immune plasma, MHAA4549A, pimodivir (JNJ-63623872), umifenovir, and HA minibinders; RSV antivirals including presatovir (GS-5806), ziresovir (AK0529), lumicitabine (ALS-008176), JNJ-53718678, JNJ-64417184, and EDP-938; broad spectrum antivirals such as favipiravir, VH244, remdesivir, and EIDD-1931/EIDD-2801; and host directed strategies including nitazoxanide, eritoran, and diltiazem. Other topics included considerations of novel endpoints such as ordinal scales and patient reported outcomes (PRO), and study design issues, and other regulatory considerations for antiviral drug development. The aim of this report is to provide a summary of the presentations given at this meeting.

negative: Emerging pathogens: the epidemiology and evolution of species jumps Novel pathogens continue to emerge in human, domestic animal, wildlife and plant populations, yet the population dynamics of this kind of biological invasion remain poorly understood. Here, we consider the epidemiological and evolutionary processes underlying the initial introduction and subsequent spread of a pathogen in a new host population, with special reference to pathogens that originate by jumping from one host species to another. We conclude that, although pathogen emergence is inherently unpredictable, emerging pathogens tend to share some common traits, and that directly transmitted RNA viruses might be the pathogens that are most likely to jump between host species.

negative: Cross-Country Comparison of Case Fatality Rates of COVID-19/SARS-COV-2 OBJECTIVES: Case fatality rates (CFR) and recovery rates are important readouts during epidemics and pandemics. In this article, an international analysis was performed on the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: Data were retrieved from accurate databases according to the user’s guide of data sources for patient registries, CFR and recovery rates were calculated for each country. A comparison of CFR between countries with total cases ≥ 1,000 was observed for 12(th) and 23(rd) March. RESULTS: Italy’s CFR was the highest of all countries studied for both time points (12(th) March, 6.22% versus 23(rd) March, 9.26%). The data showed that even though Italy was the only European country reported on 12(rd) March, Spain and France had the highest CFR of 6.16 and 4.21%, respectively, on 23(rd) March, which was strikingly higher than the overall CFR of 3.61%. CONCLUSION: Obtaining detailed and accurate medical history from COVID-19 patients, and analyzing CFR alongside the recovery rate, may enable the identification of the highest risk areas so that efficient medical care may be provided. This may lead to the development of point-of-care tools to help clinicians in stratifying patients based on possible requirements in the level of care, to increase the probabilities of survival from COVID-19 disease.

negative: SARS-CoV-2 and COVID-19: The most important research questions Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.

negative: Evaluation of Commercial Diagnostic Assays for the Specific Detection of Avian Influenza A (H7N9) Virus RNA Using a Quality-Control Panel and Clinical Specimens in China A novel avian influenza A H7N9-subtype virus emerged in China in 2013 and threatened global public health. Commercial kits that specifically detect avian influenza A (H7N9) virus RNA are urgently required to prepare for the emergence and potential pandemic of this novel influenza virus. The safety and effectiveness of three commercial molecular diagnostic assays were evaluated using a quality-control panel and clinical specimens collected from over 90 patients with confirmed avian influenza A (H7N9) virus infections. The analytical performance evaluation showed that diverse influenza H7N9 viruses can be detected with high within- and between-lot reproducibility and without cross-reactivity to other influenza viruses (H1N1 pdm09, seasonal H1N1, H3N2, H5N1 and influenza B). The detection limit of all the commercial assays was 2.83 Log(10) copies/μl [0.7 Log(10)TCID(50)/mL of avian influenza A (H7N9) virus strain A/Zhejiang/DTID-ZJU01/2013], which is comparable to the method recommended by the World Health Organization (WHO). In addition, using a WHO-Chinese National Influenza Center (CNIC) method as a reference for clinical evaluation, positive agreement of more than 98% was determined for all of the commercial kits, while negative agreement of more than 99% was observed. In conclusion, our findings provide comprehensive evidence for the high performance of three commercial diagnostic assays and suggest the application of these assays as rapid and effective diagnostic tools for avian influenza A (H7N9) virus in the routine clinical practice of medical laboratories.

negative: Social Media as a Sensor of Air Quality and Public Response in China BACKGROUND: Recent studies have demonstrated the utility of social media data sources for a wide range of public health goals, including disease surveillance, mental health trends, and health perceptions and sentiment. Most such research has focused on English-language social media for the task of disease surveillance. OBJECTIVE: We investigated the value of Chinese social media for monitoring air quality trends and related public perceptions and response. The goal was to determine if this data is suitable for learning actionable information about pollution levels and public response. METHODS: We mined a collection of 93 million messages from Sina Weibo, China’s largest microblogging service. We experimented with different filters to identify messages relevant to air quality, based on keyword matching and topic modeling. We evaluated the reliability of the data filters by comparing message volume per city to air particle pollution rates obtained from the Chinese government for 74 cities. Additionally, we performed a qualitative study of the content of pollution-related messages by coding a sample of 170 messages for relevance to air quality, and whether the message included details such as a reactive behavior or a health concern. RESULTS: The volume of pollution-related messages is highly correlated with particle pollution levels, with Pearson correlation values up to .718 (n=74, P<.001). Our qualitative results found that 67.1% (114/170) of messages were relevant to air quality and of those, 78.9% (90/114) were a firsthand report. Of firsthand reports, 28% (32/90) indicated a reactive behavior and 19% (17/90) expressed a health concern. Additionally, 3 messages of 170 requested that action be taken to improve quality. CONCLUSIONS: We have found quantitatively that message volume in Sina Weibo is indicative of true particle pollution levels, and we have found qualitatively that messages contain rich details including perceptions, behaviors, and self-reported health effects. Social media data can augment existing air pollution surveillance data, especially perception and health-related data that traditionally requires expensive surveys or interviews.

negative: Understanding Coronavirus Since the identification of the first cases of the coronavirus in December 2019 in Wuhan, China, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', officially named SARS-CoV-2, and the cause of the disease COVID-19 Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the newly emerging virus and the inconsistent public health measures across different countries, have all served to increase the level of anxiety in the population Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? What can we do to stop its spread? Written by a leading expert, this concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience

negative: Viral Etiology of Chronic Obstructive Pulmonary Disease Exacerbations during the A/H1N1pdm09 Pandemic and Postpandemic Period Viral infections are one of the main causes of acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Emergence of A/H1N1pdm influenza virus in the 2009 pandemic changed the viral etiology of exacerbations that were reported before the pandemic. The aim of this study was to describe the etiology of respiratory viruses in 195 Spanish patients affected by AE-COPD from the pandemic until the 2011-12 influenza epidemic. During the study period (2009–2012), respiratory viruses were identified in 48.7% of samples, and the proportion of viral detections in AE-COPD was higher in patients aged 30–64 years than ≥65 years. Influenza A viruses were the pathogens most often detected during the pandemic and the following two influenza epidemics in contradistinction to human rhino/enteroviruses that were the main viruses causing AE-COPD before the pandemic. The probability of influenza virus detection was 2.78-fold higher in patients who are 30–64 years old than those ≥65. Most respiratory samples were obtained during the pandemic, but the influenza detection rate was higher during the 2011-12 epidemic. There is a need for more accurate AE-COPD diagnosis, emphasizing the role of respiratory viruses. Furthermore, diagnosis requires increased attention to patient age and the characteristics of each influenza epidemic.

negative: What are the Underlying Transmission Patterns of COVID-19 Outbreak? – An Age-specific Social Contact Characterization Abstract Background COVID-19 has spread to 6 continents. Now is opportune to gain a deeper understanding of what may have happened. The findings can help inform mitigation strategies in the disease-affected countries. Methods In this work, we examine an essential factor that characterizes the disease transmission patterns: the interactions among people. We develop a computational model to reveal the interactions in terms of the social contact patterns among the population of different age-groups. We divide a city's population into seven age-groups: 0-6 years old (children); 7-14 (primary and junior high school students); 15-17 (high school students); 18-22 (university students); 23-44 (young/middle-aged people); 45-64 years old (middle-aged/elderly people); and 65 or above (elderly people). We consider four representative settings of social contacts that may cause the disease spread: (1) individual households; (2) schools, including primary/high schools as well as colleges and universities; (3) various physical workplaces; and (4) public places and communities where people can gather, such as stadiums, markets, squares, and organized tours. A contact matrix is computed to describe the contact intensity between different age-groups for each of the four settings. By integrating the four contact matrices with the next-generation matrix, we quantitatively characterize the underlying transmission patterns of COVID-19 among different populations. Findings We focus our study on 6 representative cities in China: Wuhan, the epicenter of COVID-19, together with Beijing, Tianjin, Hangzhou, Suzhou, and Shenzhen, which are five major cities from three key economic zones. The results show that the social contact-based analysis can readily explain the underlying disease transmission patterns as well as the associated risks (including both confirmed and unconfirmed cases). In Wuhan, the age-groups involving relatively intensive contacts in households and public/communities are dispersedly distributed. This can explain why the transmission of COVID-19 in the early stage mainly took place in public places and families in Wuhan. We estimate that Feb. 11, 2020 was the date with the highest transmission risk in Wuhan, which is consistent with the actual peak period of the reported case number (Feb. 4-14). Moreover, the surge in the number of new cases reported on Feb. 12-13 in Wuhan can readily be captured using our model, showing its ability in forecasting the potential/unconfirmed cases. We further estimate the disease transmission risks associated with different work resumption plans in these cities after the outbreak. The estimation results are consistent with the actual situations in the cities with relatively lenient control policies, such as Beijing, and those with strict control policies, such as Shenzhen. Interpretation With an in-depth characterization of age-specific social contact-based transmission, the retrospective and prospective situations of the disease outbreak, including the past and future transmission risks, the effectiveness of different interventions, and the disease transmission risks of restoring normal social activities, are computationally analyzed and reasonably explained. The conclusions drawn from the study not only provide a comprehensive explanation of the underlying COVID-19 transmission patterns in China, but more importantly, offer the social contact-based risk analysis methods that can readily be applied to guide intervention planning and operational responses in other countries, so that the impact of COVID-19 pandemic can be strategically mitigated. Funding General Research Fund of the Hong Kong Research Grants Council; Key Project Grants of the National Science Foundation of China.

negative: Chapter 6 Public Health, Communicable Diseases and Global Health Public health professionals are considering how molecular medicine applications can impact on preventive medicine and health provision enabling interventions to start earlier. There is the potential for molecular medicine to improve the workplace although inappropriate use will lead to discrimination. The public health issue of communicable diseases is being addressed through molecular medicine in more effective and early detection and a better understanding of pathogenesis. A threat from emerging and re-emerging infections requires multiple approaches but early and definitive detection will need nucleic acid based approaches. The non-communicable diseases are now a global world problem, particularly obesity. While molecular medicine is still to make a significant impact on this disorder some interesting findings are emerging about the role of genes in obesity. Ultimately, global health issues must include more efficient and environmentally sustainable strategies. Molecular technologies provide a promising approach for the way forward. Keywords Epidemiology, workplace, diagnostics, resistance, virulence, emerging and re-emerging infections, obesity, bioeconomy

negative: Upper respiratory virus detection without parent-reported illness in children is virus-specific Abstract Background Viral upper respiratory tract infection (vURI) may or may not present with a cold/flu-like illness (CFLI). Objectives For common upper respiratory viruses that cause vURIs, to determine the relative frequencies of virus detection by PCR in subjects with and without CFLIs. Study design Prospective follow-up of 170 children aged 1–8.6 years through the CFLI season by daily parental diary for CFLI episodes and nasal secretion sampling using PCR assays for adenovirus, coronavirus (types 229E and OC43), influenza virus (types A and B), parainfluenza (types 1–3) virus, rhinovirus, and respiratory syncytial virus (RSV). Results Virus was detected in 415 of 956 independent assays: 425 CFLI episodes and 531 non-CFLI periods were sampled; samples from 270 (64%) CFLI episodes and 145 (27%) non-CFLI periods contained virus detected by PCR. Rhinovirus was most frequently detected at 64%, followed by mixed viruses at 12%, RSV at 7%, and the other viruses at 3–5% of all detections. About 85% of RSV, influenza A and adenovirus detections were associated with a CFLI, whereas less than 62% of other virus detections were associated with CFLI. Conclusions The frequency of PCR virus detection without CFLI was different among viruses. This introduces virus-specific biases to estimating the frequencies of specific complications attributable to a vURI when ascertained by CFLI identification.

negative: SARS-CoV and IFN: Too Little, Too Late Dysregulated type I interferon (IFN-I) expression can lead to severe pathology and disease. In this issue of Cell Host & Microbe, Channappanavar et al. (2016) use a SARS-coronavirus animal model to describe how rapid and robust virus replication with delayed IFN-I can lead to lung immunopathology, with fatal outcomes.

negative: A single recombinant anti-RhD IgG prevents RhD immunization: association of RhD-positive red blood cell clearance rate with polymorphisms in the FcgammaRIIA and FcgammaIIIA genes. A single recombinant immunoglobulin G1 (IgG1) anti-RhD antibody (MonoRho) was compared with a currently used polyclonal anti-RhD product (Rhophylac) in a phase 1 study for safety, efficacy of Rhesus D (RhD)-positive red blood cell (RBC) clearance, and prevention of RhD immunization in RhD-negative men challenged with 15 mL RhD-positive RBCs. Both the polyclonal product and recombinant anti-RhD effectively cleared RhD-positive RBCs after intravenous and intramuscular injection. The recombinant anti-RhD demonstrated a slower clearance rate compared with the polyclonal anti-RhD. There was no dose response, and there was considerable variation among subjects who received the same dose of recombinant anti-RhD. Interestingly, RhD-positive RBC clearance rates were strongly associated with Fcgamma receptor IIA (FcgammaRIIA) and FcgammaIIIA but not with FcgammaIIIB polymorphisms. Subjects homozygous for FcgammaRIIA-131H or FcgammaRIIIA-158V allotypes showed a faster clearance rate compared with both the heterozygote and the corresponding alternative homozygote allotypes. A similar but less marked trend was seen for the polyclonal anti-RhD. Despite the variation in clearance rates there was no evidence of anti-RhD alloantibodies in any of the subjects at +6 months after the RBC challenge.

negative: Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets Humans may be infected by different influenza A viruses—seasonal, pandemic, and zoonotic—which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues—including the central nervous system—for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.

negative: Waiting for the Flu: Cognitive Inertia and the Spanish Influenza Pandemic of 1918–19 This study looks at public awareness and understanding of the Spanish flu in the United States between June 1918, when the flu became “Spanish,” and the end of September when the deadly second wave reached the majority of the country. Based on an extensive reading of local newspapers, it finds a near universal lack of preparation or panic or other signs of personal concern among those in the unaffected areas, despite extensive and potentially worrying coverage of the flu's progress. The normal reaction to news of the inexorable approach of a pandemic of uncertain virulence is anxiety and action. The Spanish flu produced neither in the uninfected areas for a month. The most likely reason appears to be cognitive inertia—the tendency of existing beliefs or habits of thought to blind people to changed realities. This inertia grew out of the widespread understanding of flu as a seasonal visitor that while frequently unpleasant almost never killed the strong and otherwise healthy. This view of the flu was powerful enough that it blinded many in the unaffected regions to the threat for weeks even in the face of daily or near daily coverage of the pandemic's spread.

negative: The world is upside down; how coronavirus changes the way we care for our patients

negative: Human Avian Influenza: How Ready Are We? Three influenza pandemics emerged in the 20th century, and scientists are concerned that the currently circulating, highly pathogenic A (H5N1) avian influenza virus could lead to the next pandemic, one as deadly as the 1918 influenza pandemic. Not since the identification of HIV and AIDS will the duty to care among health care providers be tested as during such an event. Nonetheless, the expertise of health care providers is an integral part of the response to a pandemic. In the fight against flu, forewarned is forearmed. This report provides an overview of avian influenza (a.k.a. bird flu) and phases of pandemic influenza, with an emphasis on what health care providers should know to be prepared for a human avian influenza outbreak and the next pandemic.

negative: COVID-19 in Latin America: Novel transmission dynamics for a global pandemic?

negative: Inevitable or avoidable? Despite the lessons of history, the world is not yet ready to face the next great plague

negative: Severe acute respiratory symptoms and severe acute respiratory syndrome

negative: Death, Demography and the Denominator:New Influenza-18 Mortality Estimates for Ireland Using the Irish experience of the Spanish flu, we demonstrate that pandemic mortality statistics are sensitive to the demographic composition of a country. We build a new demographic database for Ireland's 32 counties with vital statistics on births, ageing, migration and deaths. We then show how age-at-death statistics in 1918 and 1919 should be reinterpreted in light of these data. Our new estimates suggest the very young were most impacted by the flu. New studies of the economic impact of Influenza-18 must better control for demographic factors if they are to yield useful policy-relevant results. Covid-19 mortality statistics must go through a similar procedure so policymakers can better target their public health interventions.

negative: Fourth meeting of the Eastern Mediterranean Acute Respiratory Infection Surveillance (EMARIS) network and first scientific conference on acute respiratory infections in the Eastern Mediterranean Region, 11–14 December, 2017, Amman, Jordan Abstract Influenza causes significant morbidity and mortality worldwide. Owing to its ability to rapidly evolve and spread, the influenza virus is of global public health importance. Information on the burden, seasonality and risk factors of influenza in countries of the World Health Organization Eastern Mediterranean Region is emerging because of collaborative efforts between countries, WHO and its partners over the past 10 years. The fourth meeting of the Eastern Mediterranean Acute Respiratory Infection Surveillance network was held in Amman, Jordan on 11–14 December 2017. The meeting reviewed the progress and achievements reported by the countries in the areas of surveillance of and response to seasonal, zoonotic and pandemic influenza. The first scientific conference on acute respiratory infection in the Eastern Mediterranean Region was held at the same time and 38 abstracts from young researchers across the Region were presented on epidemiological and virological surveillance, outbreak detection and response, influenza at the animal-human interface, use and efficacy of new vaccines to control respiratory diseases and pandemic influenza threats. The meeting identified a number of challenges and ways to improve the quality of the surveillance system for influenza, sustain the system so as to address pandemic threats and use the data generated from the surveillance system to inform decision-making, policies and practices to reduce the burden of influenza-associated illnesses in the Region.

negative: Avian influenza virus (H5N1): a threat to human health. Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, and the next pandemic may well arise from a low-pathogenicity virus. The rationale for particular concern about an H5N1 pandemic is not its inevitability but its potential severity. An H5N1 pandemic is an event of low probability but one of high human health impact and poses a predicament for public health. Here, we review the ecology and evolution of highly pathogenic avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of human H5N1 disease in relation to its epidemiology, clinical presentation, pathogenesis, diagnosis, and management.

negative: Economic Implications of Influenza and Influenza Vaccine The objective of this chapter is to review and summarize the current economic estimates of influenza and the cost-effectiveness of its vaccines. We reviewed the published assessments of the economic costs of human seasonal and pandemic influenza internationally. Seasonal influenza costs Germany, France, and the USA between $4 and $87 billion annually. Depending upon the intensity of transmission and severity of disease, pandemic influenza may cause as many as 350 million deaths and result in economic losses topping $1 trillion – an impact great enough to create a worldwide recession. We then reviewed 100 papers primarily from more than a dozen countries which studied the cost-effectiveness of influenza vaccine in children, adults, and the elderly. These studies demonstrate that influenza vaccination is quite cost-effective among children 6 months to 18 years old, in health care workers and pregnant women, and in high-risk individuals. Remarkably, compared with the other recently introduced vaccines for children, such as rotavirus and pneumococcal polysaccharide, vaccinating children and school attendees results in societal cost savings because it obviates lost productivity and wages among infected individuals and their caretakers. Vaccination for children is recommended in the USA and in Canada, but public health policy makers in Europe have undervalued this vaccine and not recommended it so widely.

negative: The Indian perspective of COVID-19 outbreak The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918-1919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.

negative: Identifying agents triggering bronchiolitis in the State of Qatar BACKGROUND: Bronchiolitis is considered as the most frequent lower respiratory tract infection in infants and young children. This disorder is marked by acute inflammation, edema, damage of epithelial cells lining small airways, and augmentation of mucus production. OBJECTIVE: The goal of the study was to identify agents triggering bronchiolitis in the State of Qatar. MATERIALS AND METHODS: A cross-sectional retrospective study was performed at Hamad Medical Corporation, the only tertiary and academic medical center in the State of Qatar. The study included infants and young children aged 0–24 months who were admitted to our pediatric ward with diagnosis of acute bronchiolitis (2010–2012) RESULTS: Eight hundred thirty-five infants and young children met the study inclusion criteria with mean age at diagnosis of 3.61±3.56 months. Respiratory virus real-time polymerase chain reaction was performed on 769 (92.0%) of the participants. Respiratory syncytial virus (RSV) was positive in 352 (45.7%) children admitted with clinical bronchiolitis. In addition, no viruses were identified in 142 (18.4%) of those admitted, and respiratory viruses other RSV were found in 275 (35.7%) of the children. Our investigations and observations show that there has been a steady and periodic seasonal variation in the RSV rate over the study period. A seasonal trend for the RSV (detected by respiratory virus real-time polymerase chain reaction) rate was evident, showing annual peaks in the months of October, November, December, and January, with a significant test for seasonality (test statistics [T]=3.15, P=0.009). CONCLUSION: In countries with desert hot weather, bronchiolitis might affect children throughout the year. Our results suggest that the combination of date regarding uninterrupted RSV seasonality can provide guidance for health care planning and application of RSV prevention scheme, such as extending the palivizumab immunoglobulin series.

negative: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012 In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner’s network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI.

negative: Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

negative: Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination. This study compared the complete genome sequences of 16 NL63 strain human coronaviruses (hCoVs) from respiratory specimens of paediatric patients with respiratory disease in Colorado, USA, and characterized the epidemiology and clinical characteristics associated with circulating NL63 viruses over a 3-year period. From 1 January 2009 to 31 December 2011, 92 of 9380 respiratory specimens were found to be positive for NL63 RNA by PCR, an overall prevalence of 1 %. NL63 viruses were circulating during all 3 years, but there was considerable yearly variation in prevalence and the month of peak incidence. Phylogenetic analysis comparing the genome sequences of the 16 Colorado NL63 viruses with those of the prototypical hCoV-NL63 and three other NL63 viruses from the Netherlands demonstrated that there were three genotypes (A, B and C) circulating in Colorado from 2005 to 2010, and evidence of recombination between virus strains was found. Genotypes B and C co-circulated in Colorado in 2005, 2009 and 2010, but genotype A circulated only in 2005 when it was the predominant NL63 strain. Genotype C represents a new lineage that has not been described previously. The greatest variability in the NL63 virus genomes was found in the N-terminal domain (NTD) of the spike gene (nt 1-600, aa 1-200). Ten different amino acid sequences were found in the NTD of the spike protein among these NL63 strains and the 75 partial published sequences of NTDs from strains found at different times throughout the world.

negative: Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic BACKGROUND: Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010. METHODS: Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. RESULTS: Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. CONCLUSIONS: Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.

negative: Rethinking Urban Epidemiology: Natures, Networks and Materialities How should we understand the relationship between urban environments and infectious diseases? This article addresses this question from three particular perspectives: that of the materialities of health, that of nature and that of networks. The first perspective analytically blends biological dynamics, environmental influence and social practice. The second perspective, mainly influenced by multispecies ethnographies, foregrounds the liveliness and unboundedness of cities. Finally, the third perspective analyses how health is drawn into the domain of security. The article argues that while globalization and urbanization are often discussed as having triggered the emergence and spread of pathogens, urban epidemics are not self‐evident and ‘natural' consequences of these pro‐cesses. They do not fall neatly into universal categories of space, modernity or risk; rather, they are produced and shaped by a range of social, political, biological and economic sites and scales. Accordingly, the emergence of pathogens depends on its articulation through specific analytical frameworks. This article suggests that a critical focus on how infectious diseases manifest themselves differently in different local contexts may not only provide insights into the manifold forms of urban life, but also into the multiple, complex and highly political constitution of health.

negative: Reading for Pandemic: Viral Modernism by Elizabeth Outka, New York: Columbia University Press, 2020

negative: Occupational health responses to COVID‐19: What lessons can we learn from SARS? On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent responsible was subsequently identified as a coronavirus—SARS‐CoV‐2. The WHO declared this disease as a Public Health Emergency of International Concern at the end of January 2020. This event evoked a sense of déjà vu, as it has many similarities to the outbreak of severe acute respiratory syndrome (SARS) of 2002‐2003. Both illnesses were caused by a zoonotic novel coronavirus, both originated during winter in China and both spread rapidly all over the world. However, the case‐fatality rate of SARS (9.6%) is higher than that of COVID‐19 (<4%). Another zoonotic novel coronavirus, MERS‐CoV, was responsible for the Middle East respiratory syndrome, which had a case‐fatality rate of 34%. Our experiences in coping with the previous coronavirus outbreaks have better equipped us to face the challenges posed by COVID‐19, especially in the health care setting. Among the insights gained from the past outbreaks were: outbreaks caused by viruses are hazardous to healthcare workers; the impact of the disease extends beyond the infection; general principles of prevention and control are effective in containing the disease; the disease poses both a public health as well as an occupational health threat; and emerging infectious diseases pose a continuing threat to the world. Given the perspectives gained and lessons learnt from these past events, we should be better prepared to face the current COVID‐19 outbreak.

negative: G6PD and chloroquine: Selecting the treatment against SARS‐CoV‐2? In light of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) pandemic and the possible widespread use of chloroquine (a member of the drug class 4-aminoquinoline primarily used to prevent and treat malaria and amebiasis) and its derivatives (e.g. hydroxychloroquine, a metabolite of chloroquine),1 a safety issue is addressed, concerning the selection of patients suitable to receive it. HCov-229E is one of the four flu-causing coronaviruses which share great sequence similitude, while many symptoms of patients infected with COVID-19 resemble those of patients infected with these known flu-causing coronaviruses.2 A previous study reported that human lung epithelial A549 cells treated with glucose 6-phosphate dehydrogenase (G6PD) interfering RNA (RNAi) to lower G6PD activity displayed augmented (12-fold) viral production in comparison to normal counterparts when infected with coronavirus HCov-229E. Moreover, viral replication in these G6PD-deficient cells was found to be 3-fold higher than normal cells, following a 10-h incubation, as estimated by quantitative polymerase chain reaction (qPCR).3 G6PD deficiency remains the most common human enzymatic disorder of red blood cells worldwide.

negative: Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children

negative: Emerging Infections and Children: Influenza and Acute Necrotizing Encephalopathy Children can play a variety of roles in emerging infectious diseases. They can be victims, as in the vertical transmission of human immunodeficiency virus infection. They can be affected in a minor way compared with adults, as in West Nile virus infection, legionellosis, and coronavirus infection leading to severe acute respiratory syndrome (SARS). Sometimes, however, they play predominant roles—sources for other age groups—as do toddlers in out-of-the-home child care for transmission of penicillinresistant pneumococci and cytomegalovirus to family members. Children have a uniquely central role in transmitting the influenza viruses that cause annual seasonal outbreaks and epidemic disease and could cause global epidemic (or pandemic) disease. Children themselves suffer excessive morbidity and mortality from influenza. Continuous minor changes in virus neuraminidase and haemagglutinin components (antigenic drift) or a major change in either (antigenic shift) render naïve children especially vulnerable. Anticipating that pandemic influenza could occur at any time because of a major change in a human strain of influenza virus or through acquisition of human transmissibility of reassortant avian influenza strain(s) (Nicholson et al., 2003), the international community of healthcare experts are collaborating increasingly, and countries are drafting influenza pandemic preparedness plans. A draft by the U.S. Department of Health and Human Services of “Pandemic Influenza Preparedness and Response Plan” was released for comment in August 2004 (http://www.hhs.gov/nvpo/pandemicplan). All plans highlight the critical importance of international surveillance, openness, and rapid response to investigate and contain emergent avian or human strains.

negative: Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses The severity and outcome of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to different viruses while controlling other experimental parameters. We compared changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to discover mechanisms of pathogenesis in the respiratory tract.

negative: A review of vaccine research and development: Human acute respiratory infections() Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.

negative: Coronavirus: Hotspot on coronavirus disease 2019 in India The novel coronavirus disease (COVID-19) or also known as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been recognized as the cause of respiratory infection in Wuhan, Hubei Province, China, in late December 2019. As of April 5, 2020, this epidemic had spread to worldwide with 12,03,485 confirmed cases, including 62,000 deaths. The World Health Organization has declared it a Global Public Health Crisis. Coronavirus causes respiratory illness coughing, sneezing, breathlessness, and fever including pneumonia. The disease is transmitted person to person through infected droplets. At present, the research on novel coronavirus is still in the primary stage. Based on the published study, we thoroughly summarize the history and origin, microbiology and taxonomy, mode of transmissions, target receptor, clinical features, diagnosis, prevention, and treatment about COVID-19. This short report writes in hope for providing platform to community and researcher dealings against with the novel coronavirus and providing a reference for further studies.

negative: Lopinavir/ritonavir is associated with pneumonia resolution in COVID-19 patients with influenza coinfection: a retrospective matched-pair cohort study BACKGROUND: During the early stages of the pandemic, some coronavirus disease (COVID-19)patients were misdiagnosed as having influenza, which aroused the concern that some deaths attributed to influenza were actually COVID-19-related. Howerver, little is known about whether coinfection with influenza contributes to severity of COVID-19 pneumonia, and the optimal therapeutic strategy for these patients. METHODS: We retrospectively studied 128 hospitalized patients with COVID-19 pneumonia. All patients were positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)positive by nucleic acid detection. 64 cases were co-infected with influenza A/B and the other 64 were influenza negative, matched by age, sex, and days from onset of symptoms. RESULTS: Among the 64 co-infected patients, 54 (84.4%) were co-infected with influenza A, and 10 (15.6%) with influenza B. The median duration of viral shedding time from admission was longer for patients with influenza coinfection (17.0 days) than for those without influenza coinfection (12.0 days) (P<0.001). The multivariable Cox proportional hazards model showed that the hazard ratio HR of resolution in lung involvement was 1.878 (P=0.020) for patients administered lopinavir/ritonavir, compared with those not administered lopinavir/ritonavir (95% confidence interval (CI) 1.103, 3.196). Among influenza co-infected patients, those treated with lopinavir/ritonavir exhibited faster pneumonia resolution within two weeks after symptom onset (37% vs 1%, P=0.001). CONCLUSIONS: There was no difference in lung involvement between influenza co-infected and non-infected groups. Lopinavir/ritonavir eliminated the difference of lung involvement between influenza co-infected and non-infected groups, indicating that lopinavir/ritonavir is associated with pneumonia resolution in COVID-19. This article is protected by copyright. All rights reserved.

negative: Acute respiratory infections, influenza-like illness and JIA: impact on disease activity and response to the influenza vaccine

negative: XXIV World Allergy Congress 2015: Seoul, Korea. 14-17 October 2015 A1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblasts Jae-Min Shin, Heung-Man Lee, Il-Ho Park A2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistamines Hyun-Sun Yoon, Gyeong Yul Park A3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndrome Margit Zeher A4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cells Katsuhiko Matsui, Saki Tamai, Reiko Ikeda A5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintest Drsushil Suri, Dranu Suri A6 Evaluation ferqency of ADHD in childhood asthma Marzieh Heidarzadeh Arani A7 Steven johnson syndrome caused by typhoid fever in a child Azwin Lubis, Anang Endaryanto A8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 Asthma Shinichiro Koga A9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012) Lee Ju Suk A10 Management of allergic disease exacerbations in pregnancy Yasunobu Tsuzuki A11 Subcutaneous immunotherapy mouse model for atopic dermatitis Seo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee A12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs? Fatma Merve Tepetam A13 Food hypersensitivity in patients with atopic dermatitis in Korea Chun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin Cho A14 Anaphylaxis caused by an ant (Brachyponera chinensis) in Japan Yoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi Aoyagi, Yuki Tsukamoto, Kazushi Konma, Motoo Matsuura, Jung-Won Park, Yoshinori Harada, Kyoung Yong Jeong, Akiko Yura, Maiko Yoshimura A15 Anti-allergic effect of anti-IL-33 by suppression of immunoglobulin light chain and inducible nitric oxide synthase Tae-Suk Kyung, Young Hyo Kim, Chang-Shin Park, Tae Young Jang, Min-Jeong Heo, Ah-Yeoun Jung, Seung-Chan Yang A16 Food hypersensitivity in patients with chronic urticaria in Korea Hye One Kim, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Jee Hee Son, Chun Wook Park, Hee Jin Cho A17 Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT) Angelika Sager, Oliver Pfaar A18 Correlation of cutaneous sensitivity and cytokine response in children with asthma Amit Agarwal, Meenu Singh, Bishnupda Chatterjee, Anil Chauhan A19 Colabomycin E, a Streptomycete-Derived Secondary Metabolite, Inhibits Proinflammatory Cytokines in Human Monocytes/Macrophages Ilja Striz, Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Alena Sekerkova, Veronika Svachova, Miroslav Petricek A20 Intravenous immunoglobluin treatment in a child with resistant atopic dermatitis: A brief review on this therapeutic regimen Hyuck Hoon Kwon, Kyu Han Kim A21 Wheat allergy is difficult to diagnose then other food allergens Suman Kumar A22 The effects of spirulina (Arthrospira platensis) dietary supplement as an adjunct therapy for children aged 7 to 14 years old with asthma: A randomized - double blind placebo controlled clinical trial Lou Ver Leigh Arciaga Manzon, Pilar Agnes Gonzalez Andaya A23 The study about cause and clinicopathological findings of injection induced dermatitis Bark-Lynn Lew, Youngjun Oh, Dongwoo Suh, Woo-Young Sim A24 IgE reactivity of recombinant allergen pac c 3 of the Asian needle ant pachycondyla chinensis Kyoung Yong Jeong, Myung-Hee Yi, Mina Son, Dongpyo Lyu, Jae-Hyun Lee, Tai-Soon Yong, Chein-Soo Hong, Jung-Won Park A25 Characterization of specific IgE antibody related to antigen 5 of echinococcus granulosus Mohammadreza Siavashi A26 Development of binary forecast model of asthma exacerbation: Asthma index Hey Suk Yun, Ha-Na Kang, Jae-Won Oh, Young Jin Choi A27 Different levels in rantes, IL-5 and TNF-á between the nasal polyps of adolescents with allergic, local allergic and non-allergic rhinitis Ha-Na Kang, Jae-Won Oh, Young Jin Choi A28 Tgfβ1 level is associated with VDR gene polymorphism in children with allergy diseases Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva, Andrey Donnikov A29 Dynamics of immunological biomarkers in children with food allergy fed goat milk formula Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva A30 Association between obesity, abdominal obesity and adiposity and the prevalence of atopic dermatitis in young Korean adults: The korea national health and nutrition examination survey, 2008–2010 Ji Hyun Lee, Young Min Park, Sang Soo Choi, Kyung Do Han, Han Mi Jung, Young Hoon Youn, Jun Young Lee, Yong Gyu Park, Seung-Hwan Lee A31 Associations of natural history and environmental factors with asthma among children in rural and urban areas of guangdong, China Zhaowei Yang, Jing Li, Mulin Feng, Marjut Roponen, Bianca Schaub, Gary WK Wong A32 The effect of CO2-enriched atmospheres to producing of allergenic pollen by ragweed Young Jin Choi, Ha-Na Kang, Jae-Won Oh A33 Application evaluation of house dust mite and components specific-IgE and IgG4 in specific immunotherapy with allergic diseases Baoqing Sun, Peiyan Zheng A34 Effect of Asian dust events on asthma according to the socioeconomic status using claim data in KOREA Yoon-Sung Park A35 TSLP downregulates human â-defensin 2 through STAT3-dependent pathway in keratinocytes Sang Wook Son A36 Effects of anti-IgE on IL-4, IL-5, IL-17, and CD19,20,200 in a case of netherton syndrome (SPINK5 mutation) Arzu Didem Yalcin, Sukran Kose, Kemal Kiraz A37 Augmentation of arginase 1 expression exacerbates airway inflammation in murine asthma models Jin-Young Lee, Sehyo Yune, Jae-Won Paeng, Mi-Jung Oh, Byung-Jae Lee, Dong-Chull Choi, Young Hee Lim, Kyoung Won Ha A38 Caregivers of children with no food allergy – their experiences and perception of the condition Kiwako Yamamoto-Hanada, Masami Narita, Masaki Futamura, Yukihiro Ohya A39 Evaluation of Drug Provocation Tests in Korean Children: A Single Center Experience Jihyun Kim, Jinwha Choi, Kwanghoon Kim, Jaehee Choi, Kangmo Ahn A40 Danyoung classification 2015 update by digital HD endoscopic evaluation SUN-HO/Brian Chang A41 Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy in polysensitized patients Lisha Li A42 Ambient desert dust and allergic symptoms: A time series analysis from a national birth cohort (JECS) Kumiko Tsuji Kanatani, Yu-Ichi Adachi A43 Individuals Allergic to Cow’s Milk Should be Vigilant When Consuming Beef Because It May be Injected Beef Shigeyuki Narabayashi, Ikuo Okafuji, Yuya Tanaka, Satoru Tsuruta, Nobue Takamatsu A44 Quality of life of chronic rhinosinusitis patients with or without nasal polyps in Korea Soo Whan Kim, Do Hyun Kim A45 House dust mite sensitization and exacerbation of asthma in the fall in children Jong-Seo Yoon, Jin Tack Kim, Hwan Soo Kim, Yoon Hong Chun, Hyun Hee Kim, Sul Mui Won A46 Evidence-based health advice for childhood eczema and household pets Kam Lun E. Hon, Chung Mo Chow, Ting Fan Leung A47 Relationship between allergic rhinitis and mental health in korea Do Hyun Kim, Soo Whan Kim A48 Oscillometric bronchodilator response in 3 to 5 years old healthy and asthmatic Filipino children Gemmalyn Esguerra, Emily Resurreccion, Kristine Elisa Kionisala, Jenni Rose Dela Cruz A49 The use of aeroallergen immunotherapy to treat eosinophilic esophagitis Muhammad Imran A50 A study of the eczema herpeticum in Korean Yun Seon Choe, Kyu Han Kim, Mira Choi A51 Specific sublingual immunotherapy in Korean patients with atopic dermatitis Byung Soo Kim, Hyun-Joo Lee, Jeong-Min Kim, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Hyun-Chang Ko, Moon-Bum Kim A52 Association between polymorphisms in bitter taste receptors genes and clinical features in Korean asthmatics Sun-Young Yoon A53 Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats Amit Kandhare A54 A kampo formula, ogi-kenchu-to, decreases side-effects of steroid ointment for infantile atopic dermatitis: Three cases report Noriko Yahiro A55 To test use of jet nebulizers NE-C802 as a drug delivery system in the children with asthma Amit Agarwal, Meenu Singh, Jasleen Kaur, Ruby Pawankar, Pankaj Pant, Sukhmanjeet Singh A56 Immunoglobulin e to allergen components of house dust mite in Korean children with allergic disease Hwan Soo Kim, Jong-Seo Yoon, Sul Mui Won, Yoon Hong Chun, Jin Tack Kim, Hyun Hee Kim A57 Effectiveness of premedication and rapid desensitization in hypersensitivity to l-asparaginase Hwan Soo Kim, Sul Mui Won, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Jin Tack Kim A58 Angioedema with Eosinophilia: The First Report from Thailand Thatchai Kampitak A59 Evaluation of anti-pruritic and anti-inflammatory effects of Korean red ginseng extract on atopic dermatitis murine model So Min Kim, Hyun Joo Lee, Hei Sung Kim, Jeong Deuk Lee, Sang Hyun Cho A60 Subcutaneous autologous serum therapy in chronic urticaria Kiran Godse A61 Allergic bronchopulmonary aspergillosis in asthma and lung tuberculosis Juwita Soekarno, Sarie Ratnasari, E. Alwi Datau, Eko Surachmanto, JC Matheos A62 Infantile eczema is associated with campylobacter and roseburia subpopulations but not microbial diversity in stool samples of Chinese newborns Ting Fan Leung, Jamie Sui-Lam Kwok, Christine Kit-Ching Tung, Man Fung Tang, Stephen Kwok-Wing Tsui, Gary WK Wong, Kam Lun Ellis Hon, Wing Hung Tam, Hing Yee Sy A63 Association between serum chitinase level and toll-like receptor polymorphisms in bakery workers Sohee Lee A64 IFN-gamma contributes to nasal polypogenesis by inducing epithelial-to-mesenchymal transition via non-smad pathway Hyun-Woo Shin, Mingyu Lee, Dae Woo Kim, Roza Khalmuratova A65 Management and education status of anaphylaxis patients who visit our emergency room (ER) Mi Yeoung Kim, Jaewon Jeong, Chansun Park A66 Hypoallergen-Encoding DNA Plasmids As Immunoprophylactic Vaccines of Shrimp Tropomyosin Hypersensitivity Christine Yee Yan Wai, Patrick S.C. Leung, Nicki Y.H. Leung, Ka Hou Chu A67 The relationship between sputum pentraxin 3 levels and childhood asthma Hee Seon Lee, Kyung Eun Lee, Jung Yeon Hong, Mi Na Kim, Min Jung Kim, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A68 The role of local antibody responses in the nasal inflammation of allergic rhinitis (AR) patients Ji Hye Kim, Hae-Sim Park, Yoo Seob Shin, Young Min Ye, Daehong Seo, Moon Gyeong Yoon, Young Mok Lee A69 A case of ofloxacin-induced anaphylaxis by non-IgE, but specific IgG4-mediated responses Daehong Seo, Ji Hye Kim, Young-Mok Lee, Young Min Ye, Hae-Sim Park A70 Serum LTE4 metabolite as a biomarker for aspirin exacerbated respiratory disease Ga Young Ban, Kumsun Cho, Seung-Hyun Kim, Yong Eun Kwon, Moon Gyeong Yoon, Ji Hye Kim, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm, Hae-Sim Park A71 Local and systemic reactions of dust mite subcutaneous immunotherapy (SCIT) among children in a tertiary care hospital Pilar Agnes Gonzalez Andaya A72 Effects of carboxymethyl glucan (CM-glucan) in children with allergic rhinitis and asthma: A randomized controlled trial Pilar Agnes Gonzalez Andaya A73 Autophagy mechanisms in patients with severe asthma: A new therapeutic target Ga Young Ban, Chang Gyu Jung, Seung-Ihm Lee, Duy Le Pham, Dong-Hyeon Suh, Eun-Mi Yang, Young Min Ye, Yoo Seob Shin, Hae-Sim Park A74 Aggravation of airway inflammation and hypperresponsiveness following nasal challenge with dermatophagoides pteronyssinus in perennial allergic rhinitis patients without symptoms of asthma Wan Jun Wang, MO Xian, Yan Qing Xie, Jing Ping Zheng, Jing Li A75 Serum 25-hydroxyvitamin d in early childhood is non-linearly associated with allergy Emma Merike Savilahti, Outi Mäkitie, Anna Kaarina Kukkonen, Sture Andersson, Heli Viljakainen, Erkki Savilahti, Mikael Kuitunen A76 Fric test in dermographism Kiran Godse A77 Neutrophil autophagy and extracellular trap could contribute to asthma severity Duy Le Pham, Ga Young Ban, Seung-Hyun Kim, Eun-Mi Yang, Hae-Sim Park, Ji-Ho Lee, Yong-Joon Chwae A78 Redox Modulation for the Treatment of Toluene Diisocyanates-Induced Lung Inflammation Li-Ming Chin, Chi-Chang Shieh A79 A case of occupational asthma and rhinitis with anaphylaxis to Korean ginseng and sanyak Ji Hye Kim, Hye-Soo Yoo, Moon Gyeong Yoon, Ga Young Ban, Ga Young Ban, Yoo Seob Shin, Young Min Ye, Hae-Sim Park A80 Factors of influencing epidermal permeability barrier defects in atopic dermatitis children Myong Soon Sung, Jin Uck Choi, Sung Won Kim, Yong Jin Hwang A81 Innate type 2 response to aspergillusfumigatus in a murine model of atopic dermatitis-like skin inflammation Arum Park, Eun Lee, Song-I Yang, Hyun-Ju Cho, Jinho Yu A82 Activin a receptor 1C may implicate in the development of sensitive skin Dong Hun Lee, Eun Ju Kim, Yeon Kyung Kim, Eun Jin Doh, Hee Chul Eun, Jin Ho Chung, Young Mee Lee, Seon Pil Jin A83 Genetic association and eQTL analyses of genes associated with allergy in atopic/non-atopic asthma Xingnan Li, Naftali Kaminski, Sally Wenzel, Eugene Bleecker, Deborah Meyers A84 Gastroscope feature and clinical characteristics in 172 cases of children with henoch-schonlein purpura Zeng Huasong A85 The role of TRPV1 in CD4+ t cell mediated inflammatory response of allergic rhinitis Ji-Hun Mo, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Jun-Sang Bae, Young-Jun Chung, Dae Woo Kim A86 A Phenotype of Rhinitis from School Children Is Associated with the Development of Bronchial Hyperresponsiveness Eun Lee, Si Hyeon Lee, Young-Ho Kim, Hyun-Ju Cho, Ho-Sung Yu, Mi-Jin Kang, Song-I Yang, Young-Ho Jung, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Ho-Jang Kwon, Soo-Jong Hong A87 Increased basal activation status was noted in adult anaphylaxis patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ji Hye Kim, Eun-Mi Yang A88 Clinical values of interferon-gamma enzyme-linked immunospot assays for management of antibiotic hypersensitivity in hospitalized patients Suda Sibunruang, Jettanong Klaewsongkram A89 VDR gene polymorphism and 25-hydroxy vitamin d levels in children with food allergy Tatiana Sentsova, Ilya Vorozhko, Anna Timopheeva, Olga Chernyak, Vera Revyakina, Andrey Sokolnikov A90 An analysis of 145 oral almond challenge tests Makoto Nisihino, Yu Okada, Noriyuki Yanagida, Motohiro Ebisawa, Sakura Sato, Kiyotake Ogura, Tomoyuki Asaumi, Kenichi Nagakura, Tetsuharu Manabe, Hirotoshi Unno A91 Effect of creatine supplementation in fish allergenic potential; A proteomics study Pedro M Rodrigues, Denise Schrama, Gadija Mohamed, Lizex Hüsselmann, Lizex Hüsselmann, Bongani Ndimba A92 Flagellin modulates the function of invariant NKT cells via dendritic cells in asthma patients Jae-Uoong Shim, Young Il Koh, Joon Haeng Rhee, Ji-Ung Jeong A93 Clinical and subclinical manifestations of allopurinol – induced severe cutaneous adverse reactions in Vietnam Dinh Van Nguyen, Hieu Chi Chu, Mui Thi Tran, Christopher Vidal, Suran Fernando, Sheryl Van Nunen, Sy Van Than A94 Time course of serum inhibitory activity for facilitated allergen-IgE binding during house dust mite immunotherapy Mulin Feng, Jing Li A95 Periostin is a novel biomarker in eosinophilic nasal polyps of chronic rhinosinusitis Dong-Kyu Kim, Seung-No Hong, Kyoung Mi Eun, Hong Ryul Jin, Dae Woo Kim A96 Dominance of Th1-response in children with refractory mycoplasma pneumoniae pneumonia Jun Bao, Yi-Xiao Bao A97 Studies on the role of CD14 polymorphism among pollen and mold induced asthmatics of kolkata, India Sanjoy Podder, Goutam Kumar, Shampa Dutta, Amlan Ghosh A98 House dust mite allergy – Indian perspective Goutam Kumar Saha, Sanjoy Podder, Salil Kumar Gupta A99 Increased expression of purinergic (P2Y12) receptor and cysteinyl leukotriene receptors in the lung tissue of a mouse model of allergic asthma Tu/Hoang Kim Trinh, Yoo Seob Shin, Hae-Sim Park, Jing-Nan Liu, Duy Le Pham A100 Autologous serum skin test in chronic idiopathic urticaria - relationship with autoimmune markers and disease severity Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim A101 Anxiety and depression levels in severe asthma patients treated with omalizumab Ömer Özbudak, Fatih Üzer A102 Economic burden of refractory chronic spontaneous urticaria on Kuwait health system Mona Al-Ahmad, Maryam Alowayesh, Norman Carroll A103 IgE-mediated maize allergy in India: A 28 kd protein responsible for food-induced allergic reaction Anand Bahadur Singh A104 Liposomal encapsulation of house dust mite allergens and dexamethasone modulates allergic response in a murine model of asthma Yordanis Pérez-Llano, María Del Carmen Luzardo Lorenzo, Wendy Ramírez González, Carlos Calcines Cruz, Rady Laborde Quintana, Alain Morejón, Virgilio Bourg, Marilé Hechavarría Stoker A105 Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells for Eosinophilic Rhinosinusitis with Nasal Polyps in a Mouse Model Jun-Sang Bae, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo A106 Second line treatments of dermographic urticaria refractory to antihistamines Keiko Hanaoka, Michihiro Hide, Akio Tanaka, Makiko Hiragun, Mikio Kawai A107 Diagnostic Value of Specific IgE to Peanut and Ara h 2 in Korean Children with Peanut Allergy Kwanghoon Kim, Kwanghoon Kim, Hye-Young Kim, Jihyun Kim, Kangmo Ahn, Youngshin Han A108 Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema Gun-Wook Kim, Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim, Margaret Song A109 Identification of an IgG1-mediated anaphylaxis marker and its application in evaluating the antigenicity of infant formulas Takeshi Matsubara, Hiroshi Iwamoto, Yuki Nakazato, Kazuyoshi Namba, Yasuhiro Takeda A110 Nitric oxide as a screening tool for evaluation of postoperative state of chronic rhinosinusitis Jae Hoon Lee, Woo Yong Bae A111 Comparison of different medical treatment options for crswnp: Doxycycline, methylprednisolone, mepolizumab, omalizumab Els De Schryver, Lien Calus, Philippe Gevaert, Thibaut Van Zele, Claus Bachert A112 Successful treatment of steroid resistant asthma model by blocking CD28 signal Akio Mori, Satoshi Kouyama, Miyako Yamaguchi, Yo Iijima, Akemi Abe-Ohtomo, Hiroaki Hayashi, Kentaroh Watai, Chihiro Mitsui, Chiyako Oshikata, Kiyoshi Sekiya, Takahiro Tsuburai, Mamoru Ohtomo, Yuma Fukutomi, Masami Taniguchi A113 Serum periostin levels was not associated with allergic rhinitis and allergic sensitization in Korean children Ju Wan Kang, Jeong Hong Kim, Jeong Hong Kim, Keun-Hwa Lee, Hye-Sook Lee, Seong-Chul Hong, Jaechun Lee A114 Roles of ADAM10 and ADAM17 in allergic rhinitis Ji Won Seo, Jae Hoon Lee, Woo Yong Bae A115 Mechanism of oral and topical polyprenol action in atopic dermatitis Ivans Sergejs Kuznecovs, Galina Kuznecova A116 Technical and clinical validation of a mobile chamber for allergen exposure tests Karl-Christian Bergmann, Torsten Zuberbier, Joseph Salame, Torsten Sehlinger, Georg Bölke A117 The association between serum lead level and total immunoglobulin e according to allergic sensitization Yoo Suk Kim, Jung Hyun Chang, Jeong Hong Kim, Ju Wan Kang A118 Clinical and laboratory characteristics of nasal obstruction dominant allergic sensitization Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A119 Nasal provocation test is useful for the diagnoses of allergic, non- allergic, and local allergic rhinitis Young-Joo Ko, Young Hyo Kim, Dae-Young Kim, Tae Young Jang A120 Aspirin facilitates the intestinal absorption and oral sensitization of food allergens in rats Tomoharu Yokooji, Taiki Hirano, Hiroaki Matsuo A121 Gestational Secondhand Smoke Exposure Could Affect Maternal n-Glycosylation and Cause Filaggrin Loss in Children with Atopic Dermatitis Galina Kuznecova, Ivans Sergejs Kuznecovs A122 Allergen specific immunotherapy in the treatment of allergic rhinitis and asthma--a randomized prospective study from kashmir valley-north of India Roohi Rasool Wani, Shafia Alam Syed, Ghulam Hassan, Ayaz Gul, Saniya Nissar, Zaffar Amin Shah A123 Sleep disorders in latin-American children with asthma and/or allergic rhinitis and normal controls Marilyn Urrutia Pereira, Carmen Fernandez, Dirceu Sole, Herberto Jose Chong Neto, Veronica Acosta, Alfonso Mario Cepeda, Mirta Alvarez Castello, Claudia Almendarez, Jose Santos Lozano Saenz, Juan C. Sisul, Nelson Rosario Filho, Antonio Castillo, Marylin Valentin Rostan, Jennifer Avila, Hector Badellino, Maria Carolina Manotas, Raúl Lázaro Castro Almarales, Mayda González León A124 Association between respiratory symptoms and exhaled nitric oxide in Afghanistan Woo Kyung Kim, Hae-Sun Yoon A125 ATP, a danger signal, activates human eosinophils via P2 purinergic receptors Takehito Kobayashi, Tooru Noguchi, Tomoyuki Soma, Kazuyuki Nakagome, Hidetomo Nakamoto, Hirohito Kita, Makoto Nagata A126 Atopic dermatitis and sleep disorders in latin American children Marilyn Urrutia Pereira, Dirceu Sole, Herberto Jose Chong Neto, Alfonso Mario Cepeda, Raúl Lázaro Castro Almarales, Juan C. Sisul, Marylin Valentin Rostan, Hector Badellino, Miguel Alejandro Medina Avalos, Antonio Castillo, Claudia Almendarez, Nelson Rosario Filho, Caridad Sanchez Silot, Jennifer Avila, Felicia Berroa Rodriguez, Jose Santos Lozano Saenz, Mirta Alvarez Castello, Carmen Fernandez A127 Der p 23: A Major House Dust Mite Allergen in Spite of Limited Release from Fecal Pellets and Prominent Protease Sensitivity Wai Tuck Soh, Alain Jacquet, Kiat Ruxrungtham, Emmanuel Nony, Maxime Le Mignon A128 Anaphylactic Reaction After Inhalation of Budesonide Mary Lee-Wong, Suzanne McClelland, Suzanne McClelland, Nanette B. Silverberg, Christian E. Song A129 Lipidomic analysis of mattress dust from urban and rural schoolchildren in China Zhaowei Yang, Jiukai Zhang, Wentao Zheng, Nanshan Zhong, Jing Li A130 Improvements in quality of life in children with allergic rhinitis after adenotonsillectomy Jung Ho Bae, Young Joo Cho, Joo Yeon Kim A131 The seasonal variation of asthma exacerbations in patients allergic to pollens in Greece Konstantinos Petalas, Dimitrios Vourdas, Christos Grigoreas A132 Whole-genome sequencing study in allergic rhinitis nuclear families Yuan Zhang A133 Effect of the production of extracellular matrix from nasal fibroblasts by eosinophils activated with airborne fungi Seung-Heon Shin, Mi-Kyung Ye, Jeong-Kyu Kim A134 The study of clinical characteristics, lung function and bronchodilator responsiveness in infants with RSV bronchiolitis Yong Feng, Yunxiao Shang A135 GIS-based association between PM10 and allergic diseases in seoul: Implication for health and environmental policy Sungchul Seo, Ji Tae Choung, Dohyeong Kim, Young Yoo, Hyunwook Lim A136 The relationship between rhinovirus and recurrent wheezing Wenjing Zhu, Chuanhe Liu, Li Sha, Li Chang, Min Zhao, Linqing Zhao, Yuan Qian, Yuzhi Chen A137 Dominancy of Staphylcoccus Aureus in the Skin of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis Min-Hye Kim, Young Joo Cho, Mina Rho, Jung-Won Kim, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Bok-Yang Pyun, Yoon-Keun Kim A138 Micronized Cellulose Powder Reduces the Dose of Locally Applied Glucocorticoids in Patients with Allergic Rhinitis Xueyan Wang A139 New strategy for atopic dermatitis therapy with modulation of calcium ion channels Woo Kyung Kim, Yu Ran Nam, Joo Hyun Nam A140 Difference in the Systemic Bacterial Composition of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis of Urine Jung-Won Kim, Min-Hye Kim, Mina Rho, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Young Joo Cho, Bok-Yang Pyun, Yoon-Keun Kim A141 Occurrence and physiological function of immune complexes of food proteins and IgA in human saliva Hiroshi Narita, Junko Hirose, Kumiko Kizu, Ayu Matsunaga A142 Association between DNA hypomethylation at IL13 gene and allergic rhinitis in house dust mite-sensitized subjects Jingyun Li, Yuan Zhang, Luo Zhang A143 Effect of dietary methyl donors on asthma and atopy is modified by MTHFR polymorphism Yean Jung Choi, Hye Lim Shin, Song-I Yang, So-Yeon Lee, Sung-Ok Kwon, Young-Ho Jung, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, Se-Young Oh, Ho-Jang Kwon, Eun Lee, Mi-Jin Kang, Soo-Jong Hong, Yun-Jeong Lee, Joonil Kim A144 The effect of TSLP in a murine model of allergic asthma Joon Young Choi, Ji Young Kang, Seok Chan Kim, Sei Won Kim, Seung Joon Kim, Young Kyoon Kim, Chin Kook Rhee, Hea Yon Lee, Hwa Young Lee, Sook Young Lee A145 Evaluation of Aspirin Hypersensitivity in Chronic Rhinosinusitis Patients Tae Kyung Koh, Sung Wan Kim, Kun Hee Lee, Chul Kwon, Joong-Saeng Jo, Sung-Hwa Dong, Young Seok Byun A146 Chronic cough without wheezing in young children as a manifestation of chronic sinusitis Charles Song A147 Expression of muscarinic receptors and effect of tiotropium bromide on chronic asthma according to age in a murine model Ji Young Kang, Hwa Young Lee, In Kyoung Kim, Sei Won Kim, Chin Kook Rhee, Seung Joon Kim, Seok Chan Kim, Sook Young Lee, Young Kyoon Kim, Soon Seog Kwon, Joon Young Choi A148 Discrimination between non-eosinophilic and eosinophilic chronic rhinosinusitis with nasal polyps Pona Park, Hong Ryul Jin, Dong-Kyu Kim, Dae Woo Kim A149 Significant reduction in allergic features in the offspring of mice supplemented with specific non-digestible oligosaccharides during lactation Astrid Hogenkamp A150 Allergenicity assessment of hydrolysed infant formula; A multicenter comparison of a mouse model and a Guinea pig model for cow’s milk allergy Leon Knippels, Betty C.a.m. Van Esch, Jolanda Van Bilsen, Prescilla V. Jeurink; Marjan Gros, Johan Garssen, Joost J Smit, Raymond H.H. Pieters A151 Clinical significance between the allergic test and serum eosinophil cationic protein Boo-Young Kim, Soo Whan Kim A152 Hydroclorothiazide-induced acute non-cardiogenic pulmonary edema Ramon Lleonart A153 A Synbiotic Mixture of Scgos/Lcfos and Bifidobacterium Breve M-16V Is Able to Restore the Delayed Colonization of Bifidobacterium Observed in C-Section Delivered Infants Christophe Lay, Kaouther Benamor, Chua Mei Chen, Jan Knol, Charmaine Chew, Voranush Chongsrisawat, Anne Goh, Wen Chin Chiang, Rajeshwar Rao, Surasith Chaithongwongwatthana, Nipon Khemapech A154 Atopic characteristics of patients with asthma-COPD overlap syndrome Ji Young Yhi, Sang-Heon Kim, Dong Won Park, Ji-Yong Moon, Tae Hyung Kim, Jang Won Sohn, Dong Ho Shin, Ho Joo Yoon, Seok Hyun Cho A155 Perceptions and practices of severe asthma and asthma-COPD overlap syndrome among specialists: A questionnaire survey Sang-Heon Kim, Ji-Yong Moon, Jae-Hyun Lee, Ga Young Ban, Sujeong Kim, Mi-Ae Kim, Joo-Hee Kim, Min-Hye Kim, Chan-Sun Park, Hyouk-Soo Kwon, Jae-Woo Kwon, Jae Woo Jung, Hye-Ryun Kang, Jong-Sook Park, Tae-Bum Kim, Heung Woo Park, You Sook Cho, Kwang-Ha Yoo, Yeon-Mok Oh A156 A case of surgical diagnosed eosinophilic enteritis with intussusception in adult patient Sang-Rok Lee A157 Reference values of total IgE in estonian children Kaja Julge, Maire Vasar, Tiia Voor, Tiina Rebane A158 A case of eosinophilic granulomatosis with polyangiitis accompanied by rapidly progressive glomerulonephritis Yu Jin Kim, Sang Min Lee, Shin Myung Kang, Sojeong Kim, Sun Young Kyung, Sung Hwan Jeong, Jeong-Woong Park, Hyunjung Hwang, Yong Han Seon, Sanghui Park, Sang Pyo Lee A159 Associations Between Infectious Diseases and Urticaria Marius Iordache A160 Sleep in infants in korea – finding of bisq survey Yeongsang Jeong, Sohee Eun, Byung Min Choi, Ji Tae Choung, Wonhee Seo A161 Increased Expression of Filaggrin, TSLP, Periostin, IL13 and IL-33 in Nasal Polyps Liang Zhang, Ruby Pawankar, Manabu Nonaka, Miyuki Hayashi, Shingo Yamanishi, Harumi Suzaki, Yasuhiko Itoh, So Watanabe, Hitome Kobayashi A162 Asymptomatic bacteruria increases the risk of edematous attacks in patients with hereditary angioedema due to C1 inhibitor deficency (C1-INH-HAE) Zsuzsanna Zotter, Henriette Farkas, Lilian Varga, Nora Veszeli, Eva Imreh, Gabor Kovacs, Marsel Nallbani A163 Gastric Erosions Cause Spontaneous Urticaria Independent of Helicobacter Pylori Semen Zheleznov, Galina Urzhumtseva, Natalia Petrova, Zhanna Sarsaniia, Nikolai Didkovskii, Torsten Zuberbier A164 The Effect of G2 Vaccine on the Gene Expression NKG2D and Receptor Presenting on the Surface of NK Cells in Peripheral Blood Nader Dashti Gerdabi, Ali Khodadadi, Zahra Abdoli, Mehri Ghafourian, Mohammad Ali Assarehzadegan, Khodayar Ghorban A165 Ethnic differences in lifetime prevalence and indoor environmental factors for childhood eczema Hyo-Bin Kim, Hui Zhou, Jeong Hee Kim, Rima Habre, Theresa Bastain, Frank Gilliland A166 A case of methazolamide-induced toxic epidermal necrolysis Jong-Wook Bae, Kyu-Hyung Han, Young-Koo Jee, Misoo Choi, Seung-Phil Hong, Seung-Hyun Kim A167 Inflammatory responses of human adipose-tissue derived stem cells to LPS and nanoparticles Hee-Kyoo Kim, Gil-Soon Choi, Jeonghoon Heo, Young-Ho Kim, Eun-Kee Park A168 Analysis of 71 Cashew Nut Oral Challenge Tests Takashi Inoue, Kiyotake Ogura, Noriyuki Yanagida, Hirotoshi Unno, Kenichi Nagakura, Tetsuharu Manabe, Tomoyuki Asaumi, Sakura Sato, Yu Okada, Motohiro Ebisawa A169 Fungal sensitization is associated with asthma exacerbation Min-Gu Kim, You Sook Cho, Tae-Bum Kim, Hee-Bom Moon, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo, Hyouk-Soo Kwon, Jaemoon Lee, Taehoon Lee A170 Individual therapeutic patient education and consultation in children with atopic dermatitis Hye-Soo Yoo, Jieun Kim, Inok Kim, Haejin Kim, Younhee Chang, Hae-Sim Park, Sooyoung Lee A171 Utility of Alpha-Lactalbumin Specific IgE Levels Using Immulite 2000 3gAllergy in Predicting Clinical Severity of Milk Allergy Kazuyo Kuzume, Munemitsu Koizumi, Koji Nishimura, Michiko Okamoto A172 Isoniazid/rifampicin-specific t-cell responses in patients with anti-tuberculosis –induced dress syndrome Seung-Hyun Kim, Young Min Ye, Gyu Young Hur, Hae-Sim Park, Sang-Heon Kim, Young-Koo Jee A173 Genetic biomarkers associated with aspirin-exacerbated respiratory disease (AERD) phenotype based on genome-wide association study Seung-Hyun Kim, Hyunna Choi, Young Min Ye, Hae-Sim Park A174 Assessment of ORAL drug provocation test in the diagnosis of NON-steroidal ANTI-inflammatory drugs hypersensitivity Bui VAN Khanh, Hieu Chi Chu, Nguyen Nhu Nguyet, Nguyen Hoang Phuong A175 Korean treatment guideline of atopic dermatitis Joo Young Roh, Hyun Jeong Kim, Jung Eun Kim, Bark-Lynn Lew, Kyung Ho Lee, Seung-Phil Hong, Yong Hyun Jang, Kui Young Park, Seong Jun Seo, Jung Min Bae, Eung Ho Choi, Ki Beom Suhr, Seung Chul Lee, Hyun-Chang Ko, Young Lip Park, Sang Wook Son, Young Jun Seo, Yang Won Lee, Sang Hyun Cho, Chun Wook Park A176 Systemic side reaction of subcutaneous immunotherapy(SCIT) for perennial allergic rhinitis Kun Hee Lee, Sung Wan Kim A177 Clinical baseline characteristics of Asian patients suffering from refractory chronic spontaneous urticaria (CSU) in three phase 3 omalizumab clinical trials Chia-Yu CHU, Derrick Aw, Young-Min Ye, Giovanni Bader, Fabrizio Dolfi, Nathalie Oliveira A178 A metagenomic approach through t-RFLP to the microbiome of asthma Jae Chol Choi, Jae Woo Jung, Hye-Ryun Kang, Kijeong Kim, Byoung Whui Choi A179 Clinical characteristics and ten-year trend of peripheral blood eosinophilia among health screening program recipients at a tertiary hospital of South Korea Jong Wook Shin, Jae Woo Jung, Jae Chol Choi, In Won Park, Byoung Whui Choi, Jae Yeol Kim A180 The prevalence of toxocariasis and diagnostic value of serologic tests in asymptomatic Korean adults Jin-Young Lee, Kyoung Won Ha, Yun-Jin Jeung, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jung Oh, Young Hee Lim A181 Cutaneous Drug Hypersensitivity Reaction in Korean Children: An Analysis of KAERS Database on 2012-2013 Eui Jun Lee, Dongin Suh, Sung-Il Woo, Hwa Jin Cho, Eun Hee Chung, Soo Youn Chung A182 Comparison of clinical characteristics, quality of life and sleep in patients with allergic rhinitis when categorised as “sneezers and runners” and “blockers” Kamal Gera, Ashok Shah A183 Role of s-nitrosoglutathione reductase (GSNOR) in the murine strain differences of airway hyperresponsiveness Jin-Young Lee, Kyoung Won Ha, Mi-Jung Oh, Young Hee Lim, Sehyo Yune, Jae-Won Paeng, Mi-Jin Jang, Byung-Jae Lee, Dong-Chull Choi A184 Protection from airway bronchoconstriction by gsno Jin-Young Lee, Mi-Jin Jang, Jae-Won Paeng, Yun-Jin Jeung, Young Hee Lim, Mi-Jung Oh, Kyoung Won Ha, Byung-Jae Lee, Dong-Chull Choi, Sehyo Yune A185 Does EIA-targeted asthma treatment improve daily physical activity of children? Takahiro Ito A186 Wheezing as a clue to the diagnosis of cough variant asthma and nonasthmatic eosinophilic bronchitis Jihye Kim, Jin-Young Lee, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jin Jang, Jae-Won Paeng, Young Eun Kim, Young Nam Kim, Yongseok Lee A187 Antagonism of microRNA-21 suppressed the airway inflammation in a mouse model of bronchial asthma Hwa Young Lee, Sook Young Lee, Soon Seog Kwon, Young Kyoon Kim, Chin Kook Rhee, Sei Won Kim, Hea Yon Lee, Joon Young Choi, In Kyoung Kim A188 Chlorhexidine anaphylaxis: A report of two cases Jose Antonio Navarro, Maria Ascension Aranzabal, Alejandro Joral, Susana Lizarza, Miguel Echenagusia, EVA Maria Lasa A189 Effects of Particulate Matter on Respiratory Allergic Diseases Considering Meteorological Factors in Busan, Korea Eun-Jung Jo, Sun-Mi Jang, Seung-Eon Song, Hae-Jung Na, Chang-Hoon Kim, Woo-Seop Lee, Hye-Kyung Park A190 Clinical characteristics of neutrophilic asthma Sachiko Miyauchi, Yoshitaka Uchida, Tomoyuki Soma, Susumu Yamazaki, Toru Noguchi, Takehito Kobayashi, Kazuyuki Nakagome, Makoto Nagata A191 Current Practice of Infants and Children with Acute Urticaria at a Single Wide Regional Emergency Medical Center Hea Lin Oh, Do Kyun Kim, Dongin Suh, Young Yull Koh A192 Discordance between sputum eosinophilia and exhaled nitric oxide Sehyo Yune, Jin-Young Lee, Byung-Jae Lee, Dong-Chull Choi, Jae-Won Paeng, Mi-Jin Jang, Jihye Kim, Young Nam Kim A193 Association between genetic polymorphisms of costimulatory molecules and antituberculosis drugs induced hepatitis Sang-Heon Kim, Sang-Hoon Kim, Jang Won Sohn, Ho Joo Yoon, Dong Ho Shin, Jae Hyung Lee, Byoung Hoon Lee, Youn-Seup Kim, Jae-Seuk Park, Young-Koo Jee A194 The prevalence of gastroesophageal reflux disease in chronic unexplained cough Sehyo Yune, Jin-Young Lee, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee, Young Eun Kim A195 Risk Factors of Allergic Rhinitis in Preschool Children and Clinical Utility of Feno Jisun Yoon A196 Relationship between serum 25-hydroxyvitamin d and asthma exacerbation severity in children Yong Feng, Li Zhang, Xuxu Cai A197 Usefulness of Specific IgE Antibody Levels to Wheat, Gluten and Ï-5 Gliadin for Wheat Allergy in Korean Children Jong-Seo Yoon, Kyunguk Jeong, Hye-Soo Yoo, Sooyoung Lee, Sooyoung Lee A198 Neutralization of stratum corneum accelerates the progress from atopic dermatitis to asthma-like lesion in flaky tail mice treated by house dust mite allergen Hae-Jin Lee, Noo Ri Lee, Bo-Kyung Kim, Minyoung Jung, Dong Hye Kim, Catharina S. Moniaga, Kenji Kabashima, Eung Ho Choi A199 Trends in oral food challenges in Japan: A six-year prospective study Noriyuki Yanagida, Sakura Sato, Chizuko Sugizaki, Motohiro Ebisawa A200 The Gut Microbiome in the Food Allergic Host Jamie Kiehm, Punita Ponda, Sherry Farzan, Jared Weiss, Claudia Elera, Catherine Destio, Cristina Sison, Annette Lee A201 Cord blood cytokines and maternal environmental exposure during pregnancy Soo Hyun Ri, Chang Hoon Lim A202 Rupatadine pharmacokinetics in Japanese healthy volunteers after single and repeated oral doses of 10, 20 and 40 mg Iñaki Izquierdo Pulido, Jorg Taubel, Georg Ferber, Eva Santamaria Masdeu A203 A safe and effective method to desensitize patients with wheat allergy Alireza Khayatzadeh, Masoud Movahedi, Motohiro Ebisawa, Mohammad Gharagozlou A204 RNA Binding Protein Hur Regulates CD4+ T Cell Differentiation and Is Required for Allergic Airway Inflammation and Normal IL-2 Homeostasis Ulus Atasoy, Patsharaporn Techasintana, Matt Gubin, Jacqueline Glascock, Suzanne Ridenhour, Joseph Magee A205 Time Trends in the Epidemiology of Recurrent Wheezing in Infants from South America Nelson Rosario Filho; Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Caroline Dela Bianca, Carolina Aranda, Dirceu Sole, Javier Mallol, Luis Garcia-Marcos, Luis Garcia-Marcos A206 Successful Cyclophosphamide Desensitization in a Pediatric Patient with Systemic Lupus Erythematosus Jennifer Toh, Yoomie Lee, Joyce Huang, Elina Jerschow, Jenny Shliozberg A207 The Fatty Acid Binding Protein Der p 13 Is a Minor House Dust Mite Allergen Able to Activate Innate Immunity Pattraporn Satitsuksanoa, Narissara Suratannon, Jongkonnee Wongpiyabovorn, Pantipa Chatchatee, Kiat Ruxrungtham, Alain Jacquet A208 Epidemiology of Stevens-Johnson Syndrome and Toxic Epidemal Necrolysis: An Administrative Database Study Min Suk Yang; Jin Yong Lee, Ja Yeun Kim, Han-Ki Park, Ju-Young Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Kyung-up Min, Chang-Han Park, Suk-Il Chang, Sook-Hee Song A209 Regional Differences of Vitamin D and Food-Induced Anaphylaxis in Korea Si-Heon Kim, Gil-Soon Choi, Su-Chin Kim, Ji Hye Kim, Ga Young Ban, Yoo Seob Shin, Hae-Sim Park, Young Min Ye A210 Triggering Factors of Atopic Dermatitis By Severity Yoon Ha Hwang A211 Clinical Features of Adverse Drug Reactions of Monoclonal Antibodies in Korea Da Woon Sim, Kyung Hee Park, Kyung Hee Park, Hye Jung Park, Hye Jung Park, Jung-Won Park, Jung-Won Park, Jae-Hyun Lee, Jae-Hyun Lee A212 Food Allergy with Eczema Is Associated with Reduced Growth in the First Four Years of Life Katrina Allen, Cara Beck, Jennifer Koplin, Melanie Matheson, Mimi Tang, Anne-Louise Ponsonby, Lyle Gurrin, Shyamali Dharmage, Melissa Wake, Vicki Mcwilliam A213 The Preliminary Study on Clinical Efficacy and Impact Factors of One Year’s Dust Mite Specific Immunotherapy in Allergic Asthma and Rhinitis Children Sensitized to Dust Mite Xiaoying Liu, Jing Wang, Li Xiang, Qun Wang A214 Lipopolysaccharide Signaling through Toll- like Receptor 4 Could be Augmented By Dermatophagoides Farinae in the Human Middle Ear Epithelial Cell Ji-Eun Lee, Dong-Young Kim, Chae-Seo Rhee, Chae-Seo Rhee A215 Drug Allergy in Pregnant Adolescents: Relation with Familial and Personal Atopy, and Substances Use Francisco Vazquez-Nava A216 Patients and Physicians Concept of Well-Controlled Asthma: Findings from Realise Asia Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, David Price, Glenn Neira, Jiangtao Lin A217 The Role of Vasoactive Intestinal Peptide in the Pathophysiology of Acute Asthma Olga Semernik A218 Comparison of Serum Cytokine Levels According to the Severity in Atopic Dermatitis Ha-Su Kim, Jin-a Jung, Ji-in Jung A219 The Different Influence on the Regulatory T Cell Response Between Subcutanous Immnuotherapy(SCIT) and Sublingual Immunotherapy(SLIT) in Children with Asthma Qing Miao, Li Xiang A220 Asthma State of Affairs in Asia: Seeing through Physicians’ and Patients’ Lenses Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, Jiangtao Lin, David Price A221 Identification of Aspirin Exacerbated Respiratory Disease (AERD) Phenotypes Using Two Step Cluster Analysis Hyun Young Lee, Hae-Sim Park, Young Min Ye, Su Chin Kim A222 Dusty Air Pollution Are Associated with an Increase Risk of Allergic Diseases in General Population Shokrollah Farrokhi, Mohammadkazem Gheiby A223 A Genome-Wide Association Study of Antituberculosis Drugs-Induced Hepatitis Sang-Heon Kim; Heung Woo Park, Sang-Hoon Kim, Young-Koo Jee A224 The Role of peroxiredoxin6 of Bronchial Epithelial Cells in Regulating Mitochondrial Function Under Oxidative Stress By Translocation to Outside Mitochondrial Membrane Sunjoo Park, Keun Ai Moon, Hyouk-Soo Kwon, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Kyoung Young Lee, Gyong Hwa Hong, Eun Hee Ha A225 Toxic and Adjuvant Effects of 3 Types of Silica Nanoparticles on Airway System Heejae Han, Hye Jung Park, Yoon Hee Park, Yoon-Jo Kim, Kangtaek Lee, Jung-Won Park, Jae-Hyun Lee A226 Procedure for Diagnostic and Selection of Immunotherapy Method for Children with Different Immunopathogenetic Phenotypes of Atopic Dermatitis Tatiana Slavyanskaya, Vladislava Derkach A227 Prediction of the Success of Our Desensitization Protocol with Symptoms and Results of a Skin Prick Test in Patients with Hypersensitivity to Platinum-Based Chemotherapy Hye Jung Park, Chein-Soo Hong, Jae-Hyun Lee, Jae-Hyun Lee, Sungryeol KIM, Sungryeol KIM, Kyung Hee Park, Kyung Hee Park, Choong-Kun Lee, Beodeul Kang, Seung-Hoon Beom, Sang Joon Shin, Minku Jung, Jung-Won Park, Jung-Won Park A228 Anti-Allergic Effect of Intralymphatic Injection of OVA-Flagelin Mixture in Mouse Model of Allergic Rhinitis Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo, Young-Jun Chung A229 Serum Periostin Level Is Higher in Respiratory Type of NSAID Hypersensitivity Than Cutaneous Type Mi-Ae Kim, Hae-Sim Park, Moon Gyeong Yoon, Young-Soo Lee, Ji Hye Kim, Ga Young Ban, Hye-Soo Yoo, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm A230 A Retrospective Analysis of Allergy Blood Testing in Beijing Children’s Hospital in the Year of 2013: A Single-Center Research Qing Miao, Li Xiang A231 Role of Nrf2 in the Allergic Airway Inflammation Differ Between BALB/c and C57BL/6 Mice Ying-Ji Li, Takako Shimizu, Hirofumi Inagaki, Yukiyo Hirata, Hajime Takizawa, Arata Azuma, Masayuki Yamamoto, Tomoyuki Kawada A232 Effect of Human Mesenchymal Stem Cell on Neutrophilic Asthma Model Min-Gu Kim, Gyong Hwa Hong, Kyoung Young Lee, Eun Hee Ha, Keun Ai Moon, Sunjoo Park, Hyouk-Soo Kwon, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo A233 Immunomodulatory Effect of Tonsil Derived Mesenchymal Stem Cells in a Mouse Model of Allergic Rhinitis Ji-Hye Kim, Ramachandran Samivel, Eun-Hee Kim, Young-Jun Chung, Ji-Hun Mo A234 Alternative Therapy Such As Yoga May be a Low Cost Tool for Improving the Quality of Life of Patient’s with Allergic Rhinitis and Asthma Soumya M. S., G. Inbaraj, R. Chellaa, Ruby Pawankar A235 Substantial Impairment of the Quality of Life in Adult Patients with Chronic Urticaria Wonsun Choi, Hae-Sim Park, Young Min Ye, Ji Hye Kim, Ga Young Ban, Yoo-Seob Shin A236 Dietary Galacto-Oligosaccharides Reduce Airway Eosinophilia and Enhance the Th2 Suppressive Effect of Budesonide in House Dust Mite-Induced Asthma in Mice Saskia Braber, Kim Verheijden, Aletta Kraneveld, Johan Garssen, Linette Willemsen, Gert Folkerts A237 Production and Characterization of Recombinant Periplaneta americana Allergens for Component Resolved Diagnosis Stephanie Eichhorn, Fatima Ferreira, Isabel Pablos, Bianca Kastner, Bettina Schweidler, Sabrina Wildner, Peter Briza, Jung-Won Park, Naveen Arora, Stefan Vieths, Gabriele Gadermaier A238 Assessment of Characteristics of Itch in Patients with Hand Eczema Sung-Min Park, Won-Ku Lee, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Byung Soo Kim A239 The Hidden Culprit: A Case of Repeated Anaphylaxis from Cremophor Hypersensitivity. Young Nam Kim, Sehyo Yune, Jin-Young Lee, Jihye Kim, Young Eun Kim, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee A240 Spectrum of Anaphylaxis in Children and Adults at Emergency Departments in Singapore Si Hui Goh, Bee Wah Lee, Jian Yi Soh A241 Improved Quality of Life through an Integrated Health Care Service for Children with Atopic Dermatitis Hyungoo Kang; Hyunhee Kim; Hye-Yung Yum A242 Criteria Combining Autologous Serum Skin Test and Clusterin for Predicting Antihistamine-Refractoriness in Patients with Chronic Spontaneous Urticaria Young Min Ye; Hae-Sim Park; Ga-Young Ban; Ji Hye Kim; Yoo Seob Shin A243 Urinary Leukotriene E4 Levels in Wheezing Infants Takumi Takizawa, Masahiko Tabata, Akira Aizawa, Hisako Yagi, Yutaka Nishida, Hirokazu Arakawa, Akihiro Morikawa, Solongo Orosoo A244 Allergic Sensitization to Whey in Mice Is Facilitated By the Mycotoxin Deoxynivalenol (DON) Saskia Braber, Marianne Bol-Schoenmakers, Peyman Akbari, Prescilla V. Jeurink, Prescilla V. Jeurink, Priscilla De Graaff, Joost J. Smit, Betty C. A. M. Van Esch, Johan Garssen, Johan Garssen, Johanna Fink-Gremmels, Raymond H. H. Pieters A245 How to Define Chronic Cough: Based on a Systematic Review of the Epidemiological Literature Gun-Woo Kim, Eun-Jung Jo, Sujeong Kim, Woo-Jung Song, Yoon-Seok Chang, Shoaib Faruqi, Ju-Young Kim, Mingyu Kang, Min-Hye Kim, Jana Plevkova, Heung Woo Park, Sang-Heon Cho, Alyn Morice, So-Hee Lee, Sun-Sin Kim, Seoung-Eun Lee A246 Asko Study: Comparison of Behavior and Habits in Diagnosis and Treatment of Adult Asthma and COPD Patients Bilun Gemicioglu, Zeynep Misirligil, Arif Hikmet Cimrin, Hakan Gunen, Tevfik Ozlu, Aykut Cilli, Levent Akyildiz, Hasan Bayram, Esra Uzaslan, Oznur Abadoglu, Mecit Suerdem A247 Changes in Pulmonary Function in the Treatment of Obesity in Children Keigo Kainuma A248 Changes of Feno and Nasal Feno Levels after Treatment in Pediatric Allergic Rhinitis Hyun-a Kim, Ha-Su Kim, Woo Yong Bae, Jin-a Jung A249 Prevalence of Vitamin D Deficiency in Exclusively Breastfed Infants in Kenya Rose Kamenwa, William Macharia, Nusrat Said A250 In-Vitro Screening of Atopy in the Indian Population: Are Current Methods Adequate, Keeping Local IgE Seroprevalence for Common Food & Inhalant Allergens in Mind? Vidya Nerurkar, Meenal Patel, Simi Bhatia A251 Usefulness of House Dust Mites Nasal Provocation Test in Asthma Inseon S Choi, Soo-Jeong Kim, Joo-Min Won, Myeong-Soo Park A252 Biomarker-Based Treatment Option for Preschool Children with Recurrent Wheeze Mizuho Nagao A253 Anti-Tuberculosis Drugs-Induced Liver Injury in Patients with Connective Tissue Diseases Dong Won Park, Jang Won Sohn, Ji Young Yhi, Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Dong Ho Shin, Ho Joo Yoon A254 Ocular Symptoms of Cedar Pollinosis in Otolaryngology Patients Yukiyoshi Hyo A255 The Clinical Characteristics of Adverse Drug Reactions Reported in a Regional University Hospital for 6 Years and the Suggestions for the Reporting System Jaechun Lee, Su Hee Kim, Eunkyoung Lee A256 Changes in Skin Prick Test Results over 3 Years in School-Aged Children Hahn Jin Jung, Jaehyun Lim, Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A257 The Analysis of Risk Factors and Features of Food Allergy in Korean Children: Nationwide Cross-Sectional Survey Kun Song Lee A258 A Sequential Indirect-Direct Bronchial Provocation Test for Diagnosis of Asthma: A Pilot Study Jaechun Lee, Sun Young Yang, Mi Young Ahn, Jong Hoo Lee, Jasmina Golez A259 Association of VDR and CYP2R1 Polymorphisms with Persistent Allergic Rhinitis in a Han Chinese Population Hui-Qin Tian, Lei Cheng, Xin-Yuan Chen A260 Associations of Metabolic Syndrome with Asthma and Atopy in Korean Adults Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Ji Young Yhi, Ho Joo Yoon, Jang Won Sohn, Dong Ho Shin, Dong Won Park A261 Clinical Manifestation and Treatment Outcome of Eosinophilic Gastroenteritis in Korean Children Won Im Cho, Jong Sub Choi, Dongin Suh, Gyeong Hoon Kang, Jin Soo Moon, Jae Sung Ko, Kyung Jae Lee, Shin Jie Choi A262 The Sensitization Model and Correlation of Bermuda and Timothy Grass Pollen Allergen in Allergic Patients in Southern China Wenting Luo, Baoqing Sun A263 A Pilot Study on the Outcomes of Respiratory Allergic Diseases at Pre-School Age in Chinese Infants with Atopic Dermatitis Qi Gao, Li Xiang, Kunling Shen A264 Activation of Toll like Receptor 1 and 6 By House Dust Mite Enhances the Expression of Tight Junction Protein in Epidermal Keratinocytes Yong Hyun Jang A265 Pollen Exposure in a Mobile Exposure Chamber: Comparing Real-Life Symptoms with Exposure Symptoms Karl-Christian Bergmann, Torsten Sehlinger, Georg Bölke, Uwe Berger, Torsten Zuberbier A266 Retrospective Analysis of the Incidence of Allergy in Patients with Contact Eczema Joanna Kolodziejczyk, Milena Wojciechowska, Anna Hnatyszyn-Dzikowska, Micha Chojnacki, Zbigniew Bartuzi A267 Effect of Fungal Sensitization in Patients with Severe Asthma Katsunori Masaki, Koichi Fukunaga, Takashi Kamatani, Kengo Ohtsuka, Takae Tanosaki, Masako Matsusaka, Takao Mochimaru, Hiroki Kabata, Soichiro Ueda, Yusuke Suzuki, Katsuhiko Kamei, Koichiro Asano, Tomoko Betsuyaku A268 SCIg Patient Preference Pump Versus Push Karlee Trafford A269 Fixed Drug Eruption Induced By Ornidazole and Diclofenac Ismet Bulut, Zeynep Ferhan Ozseker A270 Transepidermal Water Loss Measurement during Infancy Can Predict the Subsequent Development of Atopic Dermatitis Kenta Horimukai, Hideaki Morita, Masami Narita, Hironori Niizeki, Kenji Matsumoto, Yukihiro Ohya, Hirohisa Saito, Shigenori Kabashima, Mai Kondo, Eisuke Inoue A271 Inhalant Allergens on Soft Toys: A Literature Review Robert Siebers, Francis FS Wu A272 Fractional Exhaled Nitric Oxide in Elderly Asthmatics Robert Siebers, Francis FS Wu, Ming-Hui Ting, Hung-En Laio, Tsung-Huai Kuo, Pei-Yuan Lee A273 Dye and Preservative Challenge in Meal-Associated Urticaria and Angioedema: A Low-Yield Diagnostic Maneuver Daniel Eugene Maddox A274 The Changes of Allergic Sensitization with Age in Children with Allergic Rhinitis Gwanghui RyuHyo Yeol Kim, Hun-Jong Dhong, Sang Duk Hong, Seung-Kyu Chung A275 Component-Specific IgE and IgG4 Levels in Milk Allergy Children Tolerated Baked Milk Products Osamu Higuchi, Yu-Ichi Adachi, Toshiko Itazawa, Yoko Adachi, Miki Hamamichi, Motokazu Nakabayashi, Yasunori Ito, Takuya Wada, Gyoukei Murakami, Miki Takao, Junko Yamamoto A276 Serum Surfactant Protein(SP)-D Level: A Potential Biomarker for Aspirin-Exacerbated Respiratory Disease Hyun Jung Jin, Moon Gyeong Yoon, Young Min Ye, Yoo-Seob Shin, Seung-Hyun Kim, Hae-Sim Park A277 Clinical Characteristics of Anaphylaxis in Korean Children Taek-Ki Min, Bok-Yang Pyun, So-Yeon Lee, Hyun Hee Kim, Gwang-Cheon Jang, Jinho Yu, Dongin Suh, Sooyoung Lee, Yong Mean Park, Jeong Hee Kim, Hye-Yung Yum, Kyung Won Kim, Hyeon-Jong Yang, Kangmo Ahn, Ji-Won Kwon, Myung Hyun Sohn, Hae Ran Lee, Jung Hyun Kwon, Kyu-Earn Kim, Soo-Jong Hong A278 Immunological Changes Induced By Intramuscular Injections of Autolologous Immunoglobulin in Patients with Severe Atopic Dermatitis Su-Mi Cho A279 Identification of Subtypes in Subjects with Mild to Moderate Airflow Limitation and Their Clinical and Socioeconomic Implications Jin Hwa Lee, Chin Kook Rhee, Hye Yun Park, Woo Jin Kim, Yong Bum Park, Kwang-Ha Yoo A280 Cephalosporin-Induced Dress (Drug Rash with Eosinophilia and Systemic Symptoms) Syndrome in a 7-Year-Old Boy Heejeong Kang, Hyeon-Jong Yang, Taek-Ki Min, Bok-Yang Pyun A281 Maternal Depression Is Associated with Children’s Asthma : An Analysis of the Fifth Korea National Health and Nutrition Examination Survey (2010-2012) Lee Ju Suk, Cheol Hong Kim A282 Increased Length of Hospitalization Associated with Infiltration on Chest Radiography in Pediatric Asthma Patients Jung Hyun Kwon, Sang Hyun Lee, Wonhee Seo A283 A Case of 16-Year-Old Boy with Smoking-Induced Acute Eosinophilic Pneumonia Kang-in Kim, Young Cheon Park, Hyeon-Jong Yang, Taek-Ki Min; Bok-Yang Pyun A284 A Case of Pranlukast Induced Anaphylactic Shock Sujeong Kim, Sun Jin, Jong-Myung Lee, Hye-Jin Jung, Jung-Wha Park A285 Comparison of Asthma-Related Outcomes Between Metabolically Healthy Obese and Metabolically Unhealthy Obese Asthma Patients Hyo-Jung Kim, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Hyouk-Soo Kwon, So Young Park, So-Young Park, Jung-Hyun Kim, Bomi Seo, Min-Gu Kim, Youn Yee Kim A286 Rick Factors Associated with Longer Length of Stay in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis Yena Lee, Taek-Ki Min, Hyeon-Jong Yang, Bok-Yang Pyun, Suk Hee Han, Suyeon Park, Jeongho Lee, Won-Ho Hahn A287 Urinary Excretion of 9Î±, 11Î(2)-Prostaglandin F(2) and Leukotriene E(4) in Patients with Exercise-Induced Bronchoconstriction Youhoon Jeon, Joo-Hee Kim, Tae-Rim Shin, Cheol-Hong Kim, In-Gyu Hyun, Jeong-Hee Choi A288 The Aeroallergen Sensitization Pattern and Effect on Airway Hyperresponsiveness in Busan, Korea Sun-Mi Jang, Hae-Jung Na, Seung-Eon Song, Hye-Kyung Park, Eun-Jung Jo A289 Multicenter Questionnaires on Current Management of Atopic Dermatitis Among Korean Patients and Caregivers Dong Hun Lee, Jin-Young Lee, Yang Park, Jae-Won Oh, Mi Hee Lee, Soo-Jong Hong, Soo-Jong Hong, So-Yeon Lee, Joon Soo Park, Dong-Ho Nahm, Hye-Yung Yum, Hye-Yung Yum A290 Der p 1, Der p 2 and Der p 10 IgE Reactivities in Allergic Rhinitis Patients in Korea Kyu Young, Dong-Young Kim A291 De-Labeling Beta-Lactam Hypersensitivity: An Experience from a Tertiary Care Hospital in Thailand Sirinoot Palapinyo; Jettanong Klaewsongkram A292 Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury Mouse Model Xing Chen, Yuting Jin, Xiaoming Hou, Fengqin Liu, Chunyan Guo, Yulin Wang A293 Analyses of the Factors behind the Negative Attitudes Toward the Administration of Adrenaline Auto-Injectors in School Settings Ikuo Okafuji, Yuya Tanaka, Shegeyuki Narabayashi, Satoru Tsuruta A294 Low Vitamin D Levels Are Related to High House Dust Mite Sensitization in Patients with Severe Atopic Dermatitis Yong Hyun Jang A295 Appendicular Skeletal Muscle Mass Index: A Potential Predictor of Skeletal Muscle Abnormality According to the Severity Airflow Limitation of COPD Jun-Hong Ahn, Dong-Won Lee, Jin Hong Chung, Hyun Jung Jin, Min-Su Sohn A296 Etiology and Clinical Feature of Oral Allergy Syndrome in Children Young a Park, Kyunguk Jeong, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Sooyoung Lee A297 Traffic-Related Pollution Levels and Poorly Controlled Asthma in Adults Ho Kim, Ja Yeun Kim A298 Anaphylaxis in Korean Children, 2009-2013 : Triggers of Anaphylaxis By Age Groups So-Yeon Lee, Taek-Ki Min, Tae-Won Song, Kangmo Ahn, Jihyun Kim, Gwang-Cheon Jang, Hyeon-Jong Yang, Bok-Yang Pyun, Ji-Won Kwon, Myung Hyun Sohn, Kyu-Earn Kim, Jinho Yu, Soo-Jong Hong, Jung-Hyun Kwon, Sung-Won Kim, Sooyoung Lee, Woo Kyung Kim, Hyung Young Kim, Hye-Young Kim, Youhoon Jeon A299 Maternal Allergy Is Associated with Acute Bronchiolitis Severity in Infant Chang Hoon Lim, Yeongsang Jeong, Su Jung Kim A300 Evaluation of Inflammatory Mediator Profiles in Sputum of Asthmatics As an Endotype for Refractory Asthma Hun Soo Chang, Jeong-Seok Heo, Da-Jeong Bae, Jong-Uk Lee, Ji-Na Kim, Chang-Gi Min, Hyun Ji Song, Jong-Sook Park, Soo Hyun Kim, Choon-Sik Park A301 Autophagy Is Associated with the Severity of Asthma in an Ovalbumin-Specific Mouse Model of Allergic Asthma Jing-Nan Liu, Youngwoo Choi, Yoo Seob Shin, Hae-Sim Park A302 Interleukin-9 and Interleukin-33 Levels in Children with Asthma Nima Rezaei, Sedigheh Bahrami Mahneh, Arezou Rezaei, Maryam Sadr, Masoud Movahedi A303 Pediatric Anaphylaxis at a University Hospital in Cheonan, Korea, 2013~2014 Jun Seak Gang, Joon Soo Park, Seung Soo Kim, Hyun Ho Bang, Kyeong Bae Park, Hye Sun Kim, Tae Ho Kim, Young Hwangbo, Hyun Jung Lee, Gyeong Hee Yoo, Young Chang Kim A304 Initial Antigen-Specific IgE Levels Predict Clinical Outcome of Rush Oral Immunotherapy for Food Anaphylaxis Sakura Sato, Noriyuki Yanagida, Motohiro Ebisawa A305 ABCC4 gene Polymorphism Is Associated with High Periostin Levels in Asthmatic Patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ri-Yeon Kim, Eun-Mi Yang A306 The Role of Clinical Phenotype and Allergen Sensitization at 2 Years As Predictors of Atopic Disorders at 5 Years Li Yuan Gabriella Nadine Lee, Marion Aw, Marion Aw, Bee Wah Lee, Bee Wah Lee, Evelyn Xiu Ling Loo, Yiong Huak Chan, Lynette Shek, Lynette Shek, I-Chun Kuo, I-Chun Kuo, Phaik Ling Quah, Phaik Ling Quah, Genevieve Llanora, Gerez Irvin A307 The Effect of Korean Red Ginseng (KRG) on Rhinovirus Infection in Human Nasal Epithelial Cells Joo Hyun Jung, Il Gyu Kang, Seon Tae Kim, Hyoungmin Park A308 The Effect of Korean Red Ginseng on the Symptoms and Allergic Inflammation in Patients with Allergic Rhinitis Seon Tae Kim, Joo Hyun Jung, Il Gyu Kang, Hyoungmin Park, Kwang-Pil Ko A309 Validation of the Newly Developed Multiple Allergen Simultaneous Test in Korea Jungsoo Lee, Howard Chu, Hemin Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee, Hong Kyu Kang A310 Assessment of Symptoms Severities of Allergic Rhinitis Patients Sensitive to Multiple Allergens in Skin Prick Test Dong Chang Lee, Geun Jeon Kim, Jae Hyung Hwang, Jin Bu Ha, Su Hee Jeong A311 Diurnal Temperature Range and Emergency Department Visits for Asthma in Korea 6 Cities Ho Kim, Shinha Hwang, Whahee Lee A312 Mannan-Binding Lectin Serum Levels in Atopic Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A313 Prevalence of Doctor Diagnosed Atopic Eczema, during 2003-2014 in KOREA ; Using Big Data of 48.1 Million South Korean Health-Care Records Gwang-Cheon Jang, Hyun-Hee Lee, Chang-Jong Lee, Huynsun Lim A314 Association of Recurrent Wheeze with Lung Function and Airway Inflammation in Preschool Children Ji-Eun Soh, Dae-Jin Song, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Gwang-Cheon Jang, Woo Kyung Kim, Young-Ho Jung, Soo-Jong Hong, Jung Yeon Shim A315 Mannan-Binding Lectin Serum Levels in Healthy Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A316 Rotanebuliser Prabhakarrao Pv, Ranjitha Nadendla A317 The Level of Serum Interleukin 13 and Interleukin 17A and Its Effect Factors in Children with Asthma Juan Fang, Jing Zhao A318 Is Vitamin D Insufficiency Also Involved in Childhood Asthma in South Korea? Dae-Jin Song, Sungchul Seo, Young Yoo, Yu-Ri Kim, Ji Tae Choung, Jee Hoo Lee A319 Collection of Nasal Secretions for Measurement of Local IgE: A Quest for the Best Method Margot Berings, Natalie De Ruyck, Claus Bachert, Philippe Gevaert, Gabriële Holtappels A320 The Role of Claudin 5 in a Murine Model of Asthma Pureun-Haneul Lee, Byeong-Gon Kim, Choon-Sik Park, George D Leikauf, An-Soo Jang A321 Claudin-4 in a Murine Model of Asthma: Modulation By Acrolein, a Highly Reactive Unsaturated Aldehyde Byeong-Gon Kim, Pureun-Haneul Lee, Choon-Sik Park, An-Soo Jang A322 Efficacy and Safety of Sublingual Immunotherapy in House Dust Mite Sensitized Children with Allergic Rhinitis Yang Park A323 The Association of Vitamine D Deficiency and Skeletal Muscle Dysfunction in Chronic Airway Disease Min-Su Sohn, Hyun Jung Jin, Dong-Won Lee, Jun-Hong Ahn, Jin Hong Chung A324 Bacteria Derived Extracellular Vesicles in Indoor Dust Is Closely Associated with Airway Disease and Lung Cancer: Analysis of Indoor Dustâ€™s Microbiome and IgG Sensitization of Indoor Bacteria Derived Extracellular Vesicles Sae-in Kim, Han-Ki Park, Do-Yeon Kim, Mina Rho, Jun-Pyo Choi, Yoon-Keun Kim A325 Clinical Care Program for Childhood Asthma (CCP-Childhood Asthma); A Multidisciplinary Team Care at Samitivej International Children’s Hospital Wasu Kamchaisatian, Thitikul Hiranras, Surinda Wongpun, Phornthip Chiraphorn, Anupan Tantachun, Wannipa Wongrassamee, Planee Vatanasurkitt, Naratip Somboonkul, Nattipat Juthacharoenwong, Surangkana Techapaitoon, Montri Tuchinda A326 Continuous B Cell Stimulation with CD40 Ligand Induce IgE Isotype Switching Jae Ho Lee, Sejin An A327 Effects of Interleukin-9 on Allergen-Specific Immunotherapy in a Mouse Model of Allergic Rhinitis Ji-Hyeon Shin, Soo Whan Kim, Si Won Kim, Jun Myung Kang, Boo-Young Kim, Byung-Guk Kim A328 Usefulness of Exhaled Nitric Oxide for Evaluating Wheeze and Airway Hyperresponsiveness in Preschool Children Jung-Won Lee, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Jung Yeon Shim A329 Systemic Cyclosporine Treatment in Hand Eczema Patients Kyung Ho Kim A330 Lipid Profiles and Adipokines in Korean Children with Atopic Dermatitis Young Yoo, Won Suck Yoon, Sungchul Seo, In Soon Kang, Jae Won Choi, Hye-Young Lim, Ji Tae Choung A331 Validation of Montelukast and Levocetirizine Combination Tablet Versus Individual Tablets in the Treatment of Moderate to Severe Persistent Allergic Rhinitis Among Adult Filipinos Seen at the Philippine General Hospital-Outpatient Department Michelle Buela A332 Efficacy of Makyokansekito on Treatment of Wheezing Lower Respiratory Tract Infection in Children: A Retrospective Study of 68 Patients Koji Nishimura A333 Serum Eosinophilia and Total IgE Are Associated with the Risk of Allergic Sensitization and Allergic Symptoms in Two Years Follow-up, Respectively Sang Chul Park, Hyo Jin Chung, Chang-Hoon Kim, Ju Wan Kang, Seong-Chul Hong, Keun-Hwa Lee, Jaechun Lee, Hye-Sook Lee, Jeong Hong Kim A334 The Sensitization to Russian Thistle on Mongolian Patients Narantsetseg Logii A335 The Association Between Air Pollution, Allergic Sensitization to Inhalant Allergens and Airway Hyperresponsiveness in Ulaanbaatar, Mongolia Munkhbayarlakh Sonomjamts, Enkhbayar Bazarsad A336 Pre-Coseasonal Treatment with a 5-Grass Pollen Sublingual Tablet in Adults Demonstrated a Reduction on Asthma Symptoms in Réunion Island Bashir Omarjee A337 Peak Expiratory Flow Rate Reference Values for Children Aged 5-14 Years Old in Beijing Urban Area Shuo LI A338 Soybean Storage Proteins As the Main Allergen in a Patient with Food-Dependent Exercise-Induced Anaphylaxis Due to Tofu Miyuki Hayashi, Ruby Pawankar, Shingo Yamanishi, Toru Igarashi, Yasuhiko Itoh A339 A Study of Allergy Skin Prick Test with Weed Pollen Oyuntsatsral Batsaikhan, B. Gantulga, B. Enkhbayar, S. Munkhbayarlakh, L.Narantsetseg A340 The Role of Neurotrophin in a Murine Model of House Dust Mite Induced Allergic Rhinitis Pei-Chi Chen, Jiu-Yao Wang A341 Mimotopes of the Major Shellfish Allergen Tropomyosin Suppress Splenocyte Proliferation and Local Cytokine Expression in a Mouse Model of Shellfish Allergy Nicki Y. H. Leung, Christine Yee Yan Wai, Patrick S.C. Leung, Ka Hou Chu A342 A Questionnaire Survey on Understanding of Atopic Dermatitis Among Korean Patients and Caregivers Eun Jin Doh, Dong Hun Lee, Mira Choi, Hyun-Sun Yoon, Kyu Han Kim, Ji Soo Lim A343 Comparison of the Dosage of Bronchodilators in the Bronchodilator Response Test in Children Ji Hyeon Baek, Man Yong Han, Seung Jin Lee, Youhoon Jeon, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin A344 The Expression and Effect of Natural Killer T Lymphocytes in Chidren with Asthma Yi Jiang, Miao Liu A345 Oral Provocation Test in Non-Steroidal Anti-Inflammatory Drug Hypersensitive Patients Referred to Singapore General Hospital Chaw Su Naing, Tze Chin Tan, Yong Yeow Chong A346 Different Phenotypes of Bhr (bronchial hyperresponsiveness) By Natural Course in Children and It’s Characteristics Young-Ho Kim, Eun Lee, Song-I Yang, Hyun-Ju Cho, Hyung Young Kim, Ji-Won Kwon, Young-Ho Jung, Byoung-Ju Kim, Ju-Hee Seo, Ho-Jang Kwon, Hyo-Bin Kim, So-Yeon Lee, Soo-Jong Hong, Soo Hyun Kim A347 Spectrum of Allergens Causing Allergic Rhinitis and Asthma in Urban Bangalore, India − a Study of 120 Patients Jacqueline Elizabeth Joseph, Soumya M. S, Ruby Pawankar, Harshitha Kumar A348 High Prevalence of Wheezing Illness and Risk Factor of Atopic Asthma Progression in Korean Preschool Children Sohyoung Yang, Sung-Il Woo A349 Clinical and Laboratory Screening of Primary Immunodeficiency Diseases: International Effects Nima Rezaei A350 The Effect of Helicobacter Pylori Infection in Atopic Individuals Sukran Kose, Basak Gol Serin, Arzu Didem Yalcin, Süheyla Serin Senger, Mehmet Erden, Ertan Serin A351 Clinical Spectrum and Natural History of Chronic Urticaria in Hong Kong Children Agnes Sze-Yin Leung, Ting Fan Leung A352 Skin Prick Test Reactivity to Common Pollen Aeroallergens in Patients with Allergic Rhinitis − in Urban Bangalore, India Harshitha Kumar, Soumya M.S., Jacqueline Elizabeth Joseph, Ruby Pawankar A353 Seasonal Patterns of Asthma-Related ED Visits and Admissions in Children and Adolescents Who Visited Emergency Rooms of Korea in 2007-2012 Eun Hee Chung A354 Prevalence of Atopic Dermatitis and Its Associated Risk Factors in Elementary School Children: A Cross-Sectional Study in Gyeonggi-Do, South Korea Eunji Kim, Young Yoo, Ji Tae Choung, Sungchul Seo, In Soon Kang, Jue Seong Lee, Ji Hyen Hwang A355 Intralymphatic Immunotherapy for Dermatophagoides Farinae, Dermatophagoides Pteronyssinus, Cat, and/or Dog Allergy in Patients with Allergic Rhinitis: 1 Year Follow-up Sang Min Lee, Joo Hyun Jung, Seung Joon Choi, Eugene Joe, Hyunjung Hwang, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A356 Respiratory Syncytial Virus Regulates IL-33 Expression in Bronchoalveolar Cells and Lung Tissue in Vivo Alina Gaisina, Igor Shilovskiy, Aleksandra Nikonova, Oleg Kamyshnikov, Musa Khaitov, Alexander Mitin, Komogorova Viktoriya, Marina Litvina, Nina Sharova A357 The Prevalence of Parent-Perceived Food Hypersensitivity in Pre-School Children Attending a Tertiary Care Hospital in Malaysia Faizah Mohamed Jamli A358 Th2 Dominant Airway Inflammation Induced By House Dust Mite Chitin Is Dependent on TNF-a and NKT Cell Da-Il Yoon, Jun-Pyo Choi, Han-Byul Choi, Yoon-Keun Kim, Hyeon-Il Choi A359 Geographic Variations in the Patterns of Sensitization to Aeroallergens in Korean Adults: A Multi-Center Study Mingyu Kang, Mi Yeoung Kim, Sujeong Kim, Eun-Jung Jo, Seoung-Eun Lee, Woo-Jung Song, Sang Min Lee, Chansun Park, Yoon-Seok Chang, Jaechun Lee, Young-Koo Jee, Inseon S Choi, Kyung-up Min, Sang-Heon Cho A360 Experimental Mouse Model of Asthma Induced By Dust Mite Dermatophagoides Pteronyssinus allergenic Extract Anton Laskin, Oleg Kamyshnikov, Alexander Babakhin, Valentina Berzhets, Musa Khaitov A361 Severe Refractory Pulmonary Complications in Children with Mycoplasma Pneumoniae Pneumonia Sejin An, Jae Ho Lee A362 Usefulness of Interactive e-Learning Education Program for Asthma Guideline Sung-Yoon Kang, Yoon-Seok Chang, Kyung-up Min, Sang-Heon Cho, Sae-Hoon Kim, Yong Eun Kwon, Young-Koo Jee, Tae-Bum Kim, Hee-Bom Moon, Hye-Kyung Park A363 Airway Inflammation Induced By House Dust Mite Derived Vesicles Is Mainly Induced By LPS Derived from Gram Negative Bacteria in Dust Mite. Sang-Yoon Kim, Jun-Pyo Choi, Han-Ki Park, Ji-Hyun Lee, Yoon-Keun Kim A364 Changes in the Recognition of Causal Allergen, Its Avoidance, and Allergen Specific Immunotherapy after Skin Prick Test / Intradermal Test, Nasal Provocation Test, and Intralymphatic Immunotherapy in Patients with Allergic Rhinitis: 1 Year Follow-up Hyunjung Hwang, Eugene Joe, Sang Min Lee, Seung Joon Choi, Joo Hyun Jung, Yong Han Seon, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A365 Laboratory Diagnostic of Staphylococcal Sensitization Natalya Khramykhoverchenko A366 Th-17 Regulatory Cytokines Enhance Neutrophil Production of IL-17 during Asthma Saleh Al Muhsen, Asma Sultana, Rabih Halwani, Ahmed Bahammam A367 Diagnostic Value of Serum Total IgE and Prediction of Cut-Off Value to Recommend Mast in Allergic Rhinitis Hyung Chae Yang, Sun Kyung Kim, Kwang Il Nam A368 Diagnostic Value of an Increase in FEV1 and/or FVC >12% and >200 mL from Baseline after Bronchodilators for Diagnosis of Asthma Jeong-Eun Kim, Ju Suk Lee, Ji Hyun Lee, Kyung Woo Kang A369 Combined Use of Fractional Exhaled Nitric Oxide and Bronchodilator Response in Predicting Future Loss of Asthma Control Among Children with Atopic Asthma Je-Kyung Kim, Youn-Soo Hahn, Jae-Yub Jung A370 Antigen-Specific IgA Plays an Important Role in Mucosal Immune Response in Allergic Children : Measurement of Secretory IgA and Antigen-Specific IgA Yosuke Baba, Sususmu Yamazaki, Eisuke Inage, Mari Mori, Yoshikazu Ohtsuka, Masato Kantake, Toshiaki Shimizu, Asuka Honjoh, Tomoaki Yokokura A371 Why Teaching Pediatrics Trainees about Anaphylaxis and Its Acute Management Is Essential: Cross Sectional Survey. Mehdi Adeli, Shaza Ali Mohammed Elhassan, Caroline Beck A372 Prevalence and Clinical Characteristics of Local Allergic Rhinitis in Children Min Sun Na, Heysung Baek, Seung Jin Lee, Ji Hyeon Baek, Jungwon Yoon, Sun Hee Choi, Young-Ho Jung, Youn Ho Shin, Man Yong Han A373 House Dust Mites Sublingual Immunotherapy Can Influence the Long-Term Evolution of Severe Atopic Dermatitis and the Progression to Respiratory Allergy. Enrico Compalati, Maurizio Marogna A374 The Positive Distribution Characteristics of 90 Food Specific IgG in Patients with Allergic Diseases Huimin Huang, Baoqing Sun, Mingyu BAI, Yiting Huo, Peiyan Zheng, Nili Wei, Wenting Luo A375 Evaluation of Serum Levels of Osteopontin As a Potential Biomarker of Immune Activation in Patients with Allergic Diseases Elisa Villa, Anand Andiappan, Rosalba Minisini, Olaf Rötzschke, Elena Boggio, Luca Gigliotti, Nausicaa Clemente, Annalisa Chiocchetti, Umberto Dianzani, Mario Pirisi A376 Prevalence of Allergic Rhinitis in 3-6-Year-Old (preschool) Children in Chiba City (urban area), Japan Fumiya Yamaide, Syuji Yonekura, Naoki Shimojo, Yuzaburo Inoue, Yoshitaka Okamoto A377 Comparative Efficacy of Combination Nebulized Salbutamol and Fluticasone Propionate and Nebulized Salbutamol in Children with Mild Moderate Asthma Attack Retno Asih Setyoningrum, Landia Setiawati, Sri Sumei, Deddy Iskandar A378 Characteristics of Children Hospitalized with Asthma in West Nusa Tenggara General Hospital Mataram Indonesia Indriyani Sang Ayu Kompiyang A379 Identification of Phenotypes in Allergic Bronchopulmonary Aspergillosis Using Cluster Analysis Tsuyoshi Oguma, Jun Tanaka, Katsuyoshi Tomomatsu, Koichiro Asano A380 The Roles of Type 2 Innate Lymphoid Cells (ILC2) in Chronic Rhinosinusitis (CRS) Keisuke Uno, Yoshinori Matsuwaki, Kazuhiro Omura, Eika Hayashi, Norifumi Tatsumi, Hirohito Kita, Nobuyoshi Otori, Hiromi Kojima A381 Respiratory Symptoms, Signs and Spirometry Indexes Comparision in 7-12 Years Old Girls in Esfahan Metropolis and Its Far Suburb Mohammadreza Fatemi Khorasgani A382 Induction of Kruppel-like Transcription Factor (KLF4&5) By Baker’s Yeast Mannan in Human Bronchial Epithelial and Smooth Muscle Cells Dukhee/Betty Lew, Kim/S. Lemessurier, Joseph/a Moore, Jeoung-Eun Park, Ae-Kyung Yi, Chi/Young Song, Kafait/U Malik A383 Korean Profile in Childhood Asthma Severity Classification Dongin Suh, Ja Kyoung Kim, Hyeon-Jong Yang, Bong-Seong Kim, Youn Ho Shin, So-Yeon Lee, Geunhwa Park, Woo Kyung Kim, Hyo-Bin Kim, Heysung Baek, Dae Hyun Lim, Dae Hyun Lim, Jin Tack Kim A384 Prevalence of Food Sensitization, IgE-Mediated and Non-IgE-Mediated Food Allergy Among Pediatric Patients Diagnosed with Autism Spectrum Disorders Aimee Lou Manalo Nano A385 Component-Resolved Diagnostic Study of Dermatophagoides Pteronyssinus Major Allergen Molecules in a Southern China Wenting Luo, Baoqing Sun A386 Risk Factors for Systemic and Local Reactions to Subcutaneous Allergen Immunotherapy Hikmet Tekin Nacaroglu, Semiha Bahceci Erdem, Ozlem Sumer, Sait Karaman, Canan Sule Unsal Karkiner, Suna Asilsoy, Ilker Gunay, Demet Can A387 Literature Review and Current Treatment Options for Cyclical Anaphylaxis Danielle Kiers A388 The Effect of Surfactant Protein D in Acute Lung Injury and Pulmonary Fibrosis Induced By Bleomycin Hsu Han Yin, Jiu-Yao Wang A389 Activation of Endothelial Cells to Release Hsp90, an Activator of the Prekallikrein-High Molecular Weight Kininogen (HK) Complex Allen Kaplan, Kusumam Joseph, Baby G. Tholanikunnel A390 The Effect of Climatic Treatment in 51 Asthmatic Children from Areas Severely Polluted Environment of Northern Moravia, Czech Republic Radim Dudek A391 Comparison of Some Vitamin Groups in Asthmatic Patients Gulden Bilgin, Hatice Surer, Aytun Sadan Kilinc, Dogan Yucel A392 Sensitization in Children with Atopic Dermatitis: A Single Center Study Ji Young Lee, Jihyun Kim, Hea-Kyoung Yang, Minji Kim, Sang-Il Lee, Kangmo Ahn A393 Staphylococcal Enterotoxin IgE Sensitization: A Risk Factor for COPD Overlap in the Elderly Asthma? Sung Do Moon, Byung-Keun Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Heung Woo Park, Hye-Ryun Kang, Woo-Jung Song, Min-Koo Kang, Ju-Young Kim, Kyonghee Sohn, Ha Kyung Won, Seoung-Eun Lee, Kyung-Mook Kim, Claus Bachert A394 The Effects of Probiotics and PparÎ(3) on the Murine Model of Allergic Asthma Miao-Hsi Hsieh, Jiu-Yao Wang A395 Adult Patients’ Views on the Design of Adrenaline Autoinjectors Helen Smith, Clare Brown, Christina Jones, Mark Davies A396 CCL22 miRNA modulated Th1 responses and induced therapeutic effects on OVA-induced mouse model of asthma Won Suck Yoon A397 Clinical, Histological, and Skin Microbiome Characteristics of Head and Neck Dermatitis in Atopic Dermatitis Hemin Lee, Howard Chu, Jungsoo Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Seo Hyeong Kim, Ji Yeon Noh, Ji Hye Kim A398 MicroRNA-432 modulates Th1 responses and induced therapeutic effects in atopic like murine model. Won Suck Yoon A399 Case Report of Near-Fatal Asthma Due to Snail Allergy in a House Dust Mite-Allergic Adult Jean-Pierre L’huillier, Jean-Eric Autegarden, Catherine Bertrand, Dominique Tardy A400 Relationship Between Gut Microbiota in the First 3 Months of Life and Infant Immune Function at Age 12 Months Intan Hakimah Ismail, Mimi Tang, Paul Licciardi, Frances Oppedisano, Robert Boyle, Roy Robins-Browne A401 A Pediatric Case of Food-Dependent Exercise-Induced Anaphylaxis Due to Spice Allergy Hisako Yagi, Harumi Koyama, Yutaka Nishida, Takumi Takizawa, Hirokazu Arakawa A402 Correlations Between Objective Severity Score and Each of the Subjective Severity Intensity in Atopic Dermatitis Hong Kyu Kang, Hemin Lee, Jungsoo Lee, Jung U Shin, Kwang Hoon Lee, Kwang Hoon Lee, Howard Chu, Chang Ook Park A403 Barrier Related Gene Mutations in Atopic Dermatitis Na Young Yoon, Hyeyoung Lee, Seong Jun Seo, Eunhee Choi, Hye-Young Wang, Minyoung Jung, Eung Ho Choi, Dong Hye Kim A404 Clinical Utility of Basophil Activation Test (BAT) in the Diagnosis of Drug Induced Anaphylaxis Joo-Hee KimYoung-Sook Jang, Jeong-Hee Choi, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A405 Feeding Shapes the Colonization of Gut Microbiota and Associated with Total IgE in Infant Mi-Jin KangDongin Suh, Eun Lee, Kil Yong Choi, Young-Ho Jung, Song-I Yang, Bong-Soo Kim, Ha-Jung Kim, Juneyoung Koh, Hyun-Jin Kim, Kangmo Ahn, Youn Ho Shin, Hyun-Ju Cho, Byoung-Ju Kim, Young-Ho Kim, Yean Jung A406 CD8(+)T Cell-Intrinsic Smad4 Suppresses Th2 Responses in the Pathogenesis of Contact Hypersensitivity Mizuko Mamura, Jeong-Hwan Yoon, Susumu Nakae, Inkyu Lee, Isao Matsumoto, Takayuki Sumida, Jin Soo Han, Katsuko Sudo, Ji Hyeon Ju A407 Immune-Modulatory Genomic Properties Differentiate Gut Microbiotas of Infants with and without Eczema Gaik Chin Yap, Wen Tso Liu, Seungdae Oh, Pei Ying Hong, Chiung Hui Huang, Marion Aw, Lynette Shek, Bee Wah Lee A408 The Effect of Medication in OSA Patients with Allergic Rhinitis Young Seok Byun, Sung Wan Kim, Tae Kyung Koh, Joong-Saeng Jo, Kun Hee Lee, Chul Kwon, Sung-Hwa Dong A409 A Case of Generalized Pustular Psoriasis Mimicking Acute Generalized Exanthematous Pustulosis Myung Shin Kim, Chansun Park A410 Anaphylaxis Caused By Gummy Jelly Ingestion: A Case Report Han Seok Cho, Min-Ju Kim, Min Ji Kim, Young Ok Park, Hye Yeong Lee, Hee Seong Kim, Eun Lee, Hyun-Ju Cho, Jinho Yu, Soo-Jong Hong, Keum Hee Hwang A411 Serum Folliculin As a Novel Biomarker for Asthma Jung-Hyun Kim, You Sook Cho, Sae-Hoon Kim, Hyouk-Soo Kwon, Mira Yoo, Hyo-Jung Kim, So-Young Park, Bomi Shin, So Young Park, Bomi Seo, Min-Gu Kim, Hee-Bom Moon, Jin-Ah Park, Tae-Bum Kim, Jaemoon Lee A412 Corticosteroid Nasal Irrigations after Endoscopic Sinus Surgery in the Management of Chronic Rhinosinusitis with Asthma Jin Hyeok Jeong, Tae Wook Kang, Han Seok Yoo, Yong Hee Cho, Seok Hyun Cho, Kyung Rae Kim A413 Capsaicin Injection in Neonatal Period Potentiates Intensity and Duration of Atopic Dermatitis of Rats. Jue Seong Lee, Sun-Ho Kee, Sewon Kim, Young Yoo, Heung Sik Na, Seung Keun Back A414 Comparison Between the Impulse Oscillometry System, Spirometry, Feno, Lung Clearance Index and Asthma Control and Exacerbation Status. Seung Jin Lee, Bo Seon Seo, Ji Hyeon Baek, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin, Man Yong Han, Mi-Ae Kim A415 The Association of Exhaled Nitric Oxide and Airway Hyperresponsiveness in Patients with and without Asthma Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A416 Effects of Air Pollution on Allergic Rhinitis in Korea Jisun Park A417 Exhaled Nitric Oxide in Korean Children with Allergic Rhinitis Seung Hyun Moon A418 A Questionnaire of Children with Asthma or Asthma and Allergic Rhinitis Rong Jun Lin, Ren Zheng Guan A419 A Case of Trimebutine-Induced Morbilliform Skin Eruption Gyeong Yul Park, Hyun-Sun Yoon A420 Comparison of Methacholine and Mannitol to Predict Exercise-Induced Bronchoconstriction in Children with Asthma Woo-Hyeok Choi, Heysung Baek A421 Different Inflammatory Mechanisms of Human Metapneumovirus and Respiratory Syncytial Virus Jin-Sung Park, Eunmi Kwon, Zac Callaway, Chang-Keun Kim, Takao Fujisawa A422 Sputum Microbiota in Chinese Adults with Eosinophilic Versus Non-Eosinophilic Asthma Qingling Zhang, Rihuang Qiu, Naijian Li, Zhaowei Yang, Jing Li, Kian Fan Chung, Nanshan Zhong A423 Which Clinical Features Are Useful in Predicting Presence of Staphylococcus Aureus colonization/Infection in Childhood Atopic Dermatitis? Kam Lun E. Hon, Yin Ching K. Tsang, Ting Fan Leung A424 Clinical Significance of Increased VEGF, TGF-Î(2)(1,) and YKL-40, a Chitinase like Protein, in Serum of the Children with Asthma Yoon Young Jang, Hai Lee Chung, Seung Gook Lee, Ji Hyun Na, Jong Hoon Lee A425 Analysis of Follow-up Results of Mannitol Challenge Test in Asthma Patients Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A426 Analysis of 68 Oral Walnut Challenge Tests Mikita Yamamoto, Sakura Sato, Noriyuki Yanagida, Ayako Ogawa, Kanako Ogura, Kyohei Takahashi, Kenichi Nagakura, Shigehito Emura, Tomoyuki Asaumi, Katsuhito Iikura, Motohiro Ebisawa, Yu Okada A427 Effectiveness of Air Filters Intervention in Allergic Rhinitis Jiaying Luo, Xiao Lan, Baoqing Sun, Zhao Chen, Guiyuan Sun, Shimin Li, Jiaqing Hu A428 The Relationship Between Airway Hyperresponsiveness to Mannitol and Atopy in Asthmatic Children Woo-Hyeok Choi, Heysung Baek A429 Anaphylactoid Reactions to N-Acetylcysteine in the Treatment of Aacetaminophen Overdose Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A430 Effect of Prenatal Maternal Distress and GSDMB Polymorphism on the Development of Recurrent Wheezing in Early Childhood: COCOA Study Yean Jung Choi, Si Hyeon Lee, Young-Ho Kim, Mi-Jin Kang, Hyun-Ju Cho, Eun Lee, Song-I Yang, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, So-Yeon Lee, Hyoung Yoon Chang, In Ae Choi, Kyung-Sook Lee, Yee-Jin Shin A431 Vitamin D Level in Allergic Rhinitis: A Systemic Review and Meta-Analysis Yoon Hee Kim, Min Jung Kim, In Suk Sol, Seo Hee Yoon, Young a Park, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Yong Ju Lee A432 Implication of Inspiratory and Expiratory Resistance and Reactance in Children with Asthma In Suk Sol, Kyu-Earn Kim, Yoon Hee Kim, Min Jung Kim, Seo Hee Yoon, Yong Ju Lee, Kyung Won Kim, Young a Park, Myung Hyun Sohn A433 The Association of Asthma Predictive Index with Asthma in Preschool Children with Recurrent Wheeze Sung Joo Park, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Yun Seok Yang, Jung Yeon Shim A434 Clinical Significance of Serum Total IgE Levels in Children with RSV-Associated Lower Respiratory Illness Yoon Young Jang, Hai Lee Chung, Ji Hye Kim, Hyun Seok Lee, Chang Ho Lee A435 Development of a Oak Pollen Emission and Transport Modeling Framework in South Korea Changbum Cho, Yun-Kyu Lim, Kyu Rang Kim, Mijin Kim, Baek-Jo Kim A436 Temperature, Humidity, and Air Pollution Affect Atopic Dermatitis Symptoms in Infants and Young Children Young-Min Kim, Youngshin Han, Jihyun Kim, Hae-Kwan Cheong, Byoung-Hak Jeon, Kangmo Ahn A437 Effects of Compound V on Pulmonary Fibrosis Model Chuang/Yao Ming, Jiu-Yao Wang, Ye/Yi Ling A438 Vitamin D Level and the Correlation with IgE in Children with Allergic Respiratory Diseases in Guangzhou China Huimin Huang, Baoqing Sun, Yun Chen, Peiyan Zheng, Nili Wei, Wenting Luo A439 Two Case Reports of Eosinophilic Gastroenteritis Associated with Allergic Disease Do Hyeong Lee, Gil-Soon Choi, Hee-Kyoo Kim, Han Su Park A440 Genome-Wide Association Study (GWAS) May Identify Common Genetic Variations Both in Immediate and Delayed Drug So-Young Park, Hyo-Jung Kim, Bomi Seo, Jung-Hyun Kim, Min-Gu Kim, Hyouk-Soo Kwon, You Sook Cho, Hee-Bom Moon, Tae-Bum Kim, Yoon Su Lee A441 Development of a Questionnaire for Secular Change of Atopic Dermatitis from Birth to 19-Year-Old. Akio Tanaka, Satoshi Morioke, Yukihiro Ohya, Naoki Shimojo, Akira Akasawa, Michihiro Hide, Hiroko Shizukawa A442 Evaluation of the Adherence Starts with Knowledge-20 (ASK-20) to Inhaled Drug in Patients with Bronchial Asthma Naoto Watanabe A443 The Epidemiology and Clinical Manifestation of Hmpv Infection in Children during Recent 4 Years: 2011-2014 Meeyong Shin, Myeong Sun Jang A444 Neutropenia Induced By Intravenous Immunoglobulin Young-Hee Nam, Yeo Myeong Noh, Dong Sub Jeon, Hee-Joo Nam, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A445 A First Case of Lymphocytic Interstitial Pneumonitis in Healthy Child Ji-in Jung, Ha-Su Kim, Hyun-a Kim, Jin-a Jung A446 Cytokine Production upon House Dust Mite Stimulation of Cord Blood Mononuclear Cells from Caesarean Section-Delivered Singaporean Infants Anne Goh, Rajeshwar Rao, Bindu Nandanan, Ruurd Van Elburg, Chua Mei Chien, Juandy Jo, Johan Garssen, Johan Garssen, Leon Knippels, Elena Sandalova, Wen Chin Chiang A447 Dress Syndrome with Acute Interstitial Nephritis Caused By Quinolone and Nonsteroidal Anti-Inflammatory Drugs Young-Hee Nam, Ji Young Juong, Soo Jin Kim, Eun Young Kim, Su Mi Lee, Young Ki Son, Hee-Joo Nam, Ki-Ho Kim, Soo-Keol Lee A448 IL-23 Roles in the Development of House Dust Mite Allergic Sensitization and Asthma Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Hyun Seung Lee, Yoon-Seok Chang, Jung-Won Park, Sang-Heon Cho, Kyung-up Min, Woo-Jung Song A449 Exposure Profile of Indoor Risk Factors in Dwellings of Children with Atopic Dermatitis Hyunwook Lim, Sungchul Seo, Ji Tae Choung, Young Yoo, Jun-Sik Park, Byung Kwan Kim A450 Epidemiological Characterization of Blood Eosinophils in the Elderly Population Ha Kyeong Won, Hye-Ryun Kang, Byung-Keun Kim, Sung Do Moon, Ju-Young Kim, So-Hee Lee, Woo-Jung Song, Heung Woo Park, Min-Koo Kang, Sun-Sin Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Kyoung Hee Sohn, Kyung-Mook Kim, Ki-Woong Kim, Hak Chul Jang A451 Stevens-Johnson Syndrome Caused By Methotrexate in the Treatment of Psoriasis Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A452 Genetic Determinants for Lung Function Growth in Asthmatic Children Ting Fan Leung, Man Fung Tang, Hing Yee Sy, Wa Cheong Chan, Wilson Wai San Tam A453 The Power of Allergen Specific Ig E in the Classification of Rhinitis, Korean National Hanes 2010 Seung Kyu Chung, Sujin Kim, Sang Duk Hong, Hyo Yeol Kim Hyo Yeol Kim, Hun-Jong Dhong, Jong in Jeong A454 Analysis of Allergen Immunotherapy Practice and PatientsÃ¢â‚¬â„¢ Knowledge and Attitude about Allergen Immunotherapy in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A455 Roles of Staphylococcal Enterotoxin B in House Dust Mite-Induced Acute Asthma Models Ji Won Lee, Mingyu Kang, Soon-Hee Kim A456 A Clinical Comparison of Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A457 The Beneficial Effect of Lactobacillus Gasseri PM-A0005 and Its Immunoregulatory Protein PMA5P40 on Milk-Induced Allergic Enteritis Yung-I Hou, Jiu-Yao Wang A458 Relationship Between Serum Folate Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Seol Jae Hee, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A459 Effects of Vitamin D in Patients with Chronic Rhinosinusitis Yuta Soma, So Watanabe, Ruby Pawankar, Ruby Pawankar, Harumi Suzaki, Harumi Suzaki, Hitome Kobayashi A460 Clinical Features of Systemic Contact Dermatitis from Ingestion of Rhus Young-Hee Nam, Chansun Park, Soo-Keol Lee A461 Sublingual Immunotherapy Efficacy in Patients with Atopic Dermatitis in Korea Jongrok Lee, Jooyoung Roh, Haryeong Ryu A462 Characteristics of Serious Adverse Drug Reactions in a Tertiary University Hospital Cheol-Woo Kim, Jae Hwa Cho, Mi Ra Eom, Ji Young Kang, Hye Gyeung Lee A463 Eyelid Dermatitis: Patch Test Results during a 15-Year Period in Korea and Evaluation of Metal Contents in Eye Shadows Hae Young Choi, Hye Jin Lee, Ju Yun Woo, Ji Yeon Byun, You Won Choi A464 Relationship Between Lipid Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A465 IL-32 in the Induced Sputum of Patients with Asthma Jae-Woo Kwon, Hun Soo Chang, Jeong-Seok Heo, Jong-Uk Lee, Jong-Sook Park, Eusom Kim, Soo Hyun Kim, Choon-Sik Park A466 Clinical Characteristics of Patients with Chromium Allergy in a Single University Hospital in Korea Hae Young Choi, Ji Yeon Byun, Ju Yun Woo, You Won Choi A467 Efficacy and Safety of Oral Acitretin in Chronic Hand Eczema Hyun-Ju Jin, Jin-Hwa Son, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Hoon-Soo Kim, Byung Soo Kim A468 Atypical Antipsychotics and Anticholinergic Agents Mimicking Anaphylaxis Sheryl Van Nunen, Dinh Van Nguyen, Anthony Elias, Susannah Olivia Lauer A469 Introducing Reach (Reliable Estimation of Atopic dermatitis in ChildHood): Novel, Questionnaire-Based Diagnostic Criteria for Childhood Atopic Dermatitis Seung-Chul Lee, Ho-June Lee, Jung Min Bae A470 Comprehensive Assessment to Identify the Causative Factors in Oral Allergy Syndrome Emi Ono A471 Comparison of Interpretation Methods in Allergic Skin Test Sung-Hwa Dong, Tae Kyung Koh, Young Seok Byun, Sung Wan Kim, Joong-Saeng Jo, Chul Kwon, Kun Hee Lee A472 Refraining Aminophylline Use Increases Hospitalization Among Children with Acute Asthma: A 10-Years Retrospective Cohort Study Li-Fan Liu A473 The Prevalence and Risk Factors of Atopic Dermatitis from Nationwide Study for Korean School Students Sunghee Lee A474 Probiotic Recombination Protein Effect on Atopic Dermatitis Wei-Leng Chen, Jiu-Yao Wang A475 Allergic Sensitization Status in Various Inflammatory Skin Diseases Youin Bae, Gyeong-Hun Park A476 Two Cases of Good’s Syndrome: A Rare Acquired Immunodeficiency Associated with Thymoma Suk Yeon Kim A477 IL-23 Has a Role to Play in the Development of Asthma in Short-Term Cigarette Smoke Exposure-Induced House-Dust Mite Allergic Model Hyun Seung Lee, Woo-Jung Song, Mingyu Kang, Han-Ki Park, Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Hye-Young Kim, Kyung-up Min, Sang-Heon Cho, Ji-Won Lee, Boram Bae, Jung-Won Park A478 The Relationship Between the Relevance of Allergic Disease and the Value of Non-Specific IgE Yasuhiro Suzuki A479 Two Caces of Prawn Allergy in Adult Patients Ismet Bulut, Zeynep Ferhan Ozseker A480 Early Gut Bifidobacterium Breve and B. Catenulatum Colonisation Differentially Modulate Eczema Risk in Children at High-Risk of Developing Allergic Disease Intan Hakimah Ismail, Robert Boyle, Paul Licciardi, Frances Oppedisano, Roy Robins-Browne, Mimi Tang A481 Effects of Chronic Repeated Exposure of Staphylococcal Enterotoxin B on Allergic Asthma Model in Mice Ji Won Lee, Hyun Seung Lee, Mingyu Kang, Da-Eun Park, Han-Ki Park, Soon-Hee Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Chang-Han Park, Suk-Il Chang, Sook-Hee Song, Kyung-up Min, Sang-Heon Cho, Boram Bae A482 Skin Prick Test Result and Allergen Immunotherapy in Children with Allergic Rhinitis Grace Shieh A483 Role of Brp-39 in RSV-Induced Airway Inflammation in Mice Min Jung Kim, Jung Yeon Hong, Seo Hee Yoon, Doo Hee Shim, In Suk Sol, Yoon Hee Kim, Mi Na Kim, Kyung Eun Lee, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Jae Myun Lee A484 Long-Term Outcomes of Twenty-Four Adults with Primary Immunodeficiency from a Single Centre in Singapore Hiok Hee Chng A485 Breast Feeding Increases the Risk of Food Sensitization but Does Not Affect Food Allergy in Young Children with Atopic Dermatitis Dong Chan Kim, Song-I Yang, Hae Ran Lee, An Deok Seo, So Yeon Lee A486 IgE Immunoadsorption Knocks Down Anaphylaxis. Alessandro Fiocchi, Maria Cristina Artesani, Paola Francalanci, Lamia Dahdah, Thomas Schreiner A487 Burden and Correlates of Cigarette Smoking and Respiratory Airway Obstruction: An Observation in Urban Adult Population of West Bengal (India) Kaushik Chakraborty A488 Blood Eosinophils Could Predict Sputum Eosinophilia? : A Comparison Between Asthma and Non-Asthmatic Chronic Cough in the Elderly Ha Kyeong Won, Ju-Young Kim, Eun-Jung Jo, Kyoung Hee Sohn, Kyung-Mook Kim, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Woo-Jung Song, Byung-Keun Kim A489 Complementary and Alternative Medicine for Allergic Rhinitis in Japan Syuji Yonekura, Yoshitaka Okamoto A490 Impact of Cognitive Impairment on Asthma Control Status in Elderly Asthmatics Gyu Young Hur, Young Min Ye, Joo-Hee Kim, Ki-Suck Jung, Junga Kim, Jae Jeong Shim, Hae-Sim Park A491 The Association Between Respiratory Tract Infection and Reactive Oxygen Stress Kazuhiro Sekimoto, Kazuko Sugai, Keiji Tsuchimoto, Hiromi Uehara, Masanori Ikeda A492 The Risk Factors and Lung Function of Current Allergic Rhinitis Due to Dust Mite Sensitization Euncho Chung, Kang Seo Park, Yean Jung Choi, Jeewon Park, Soo-Jong Hong, So Yeon Lee A493 Cloning and Expression of Recombinant Blomia Tropicalis Dust Mite Allergen Blo t 7 Alain Jacquet, Arun Buaklin, Nat Malainual A494 Seasonal Variations of Airborne Pollen in Bangalore, India Roopashree S A495 Pollen Observation and Use of Data Kyu Rang Kim, Mijin Kim, Changbum Cho, Baek-Jo Kim, Jae-Won Oh, Mae Ja Han A496 The Effect of Cord Serum 25-Hydroxyvitamin D (25(OH)D) on the Development of Atopic Dermatitis in First 3 Years of Life : Cocoa Study Hyun-Ju Cho, Youn Ho Shin, Eun Lee, Young-Ho Kim, Darae Lee, Mi-Jin Kang, Song-I Yang, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, Hye-Sung Won, Soo Hyun Kim, Suk-Joo Choi, Young Han Kim, Jong Kwan Jun, Eun-Jin Kim, Jeom Gyu Lee, So-Yeon Lee, Soo-Jong Hong, Dongin Suh A497 Contribution of Stem Cell Factor Autocrine/Paracrine Mechanism to Aberrant Proliferation of Mast Cells Yosuke Amagai, Akane Tanaka, Hiroshi Matsuda A498 A Randomized Dbpc Dose-Finding Multicenter Trial of Sublingual Immunotherapy (SLIT) Allergoid Tablets in House Dust Mites (HDM) Allergic Patients Ralph Mösges, Pauline Dieterich, Anatoli Astvatsatourov, Christoph Hüser, Jaswinder Singh, Kija Shah-Hosseini, Silke Allekotte, Enrico Compalati A499 Depression and Allergy in the Elderly: A Community Population Analysis Kyoung Hee Sohn, Woo-Jung Song, Byung-Keun Kim, Ju-Young Kim, Min Suk Yang, So-Hee Lee, Sae-Hoon Kim, Hye-Ryun Kang, Heung Woo Park, Sun-Sin Kim, Kyung-up Min, Sang-Heon Cho, Yoon-Seok Chang A500 The Integrated Analysis of Correlation Between Total IgE and Other Immunological Factors in Allergic Diseases Woo-Sung Chang, Ji-Hye Do, Yeon-Seop Kim, Dankyu Yoon, Hye-Sun Lim, Jeom-Kyu Lee, Eun-Jin Kim A501 Pattern of Allergic Diseases Among Military Servicemen Referred to a Clinical Immunology/Allergy Service in Singapore Bernard Thong, Yew Kuang Cheng, Jinfeng Hou, Khai Pang Leong, Justina Tan, Faith Chia, Grace Chan, Sze-Chin Tan, Teck Choon Tan, Chwee Ying Tang, Hiok Hee Chng A502 A Case of Rifampicin-Induced Hypersensitivity Diagnosed By the Lymphocyte Activation Test with Successful Desensitization Chan-Sun Park, Mi Yeoung Kim, Eun-Young Kim, Jae-Gook Shin, Jae-Hyeog Choi, Saegwang Park, Yeonye Kim A503 Analysis of Individual Case Safety Reports of Drug-Induced Anaphylaxis Based on Korea Adverse Event Reporting System Database Kyung-Hwan Lim, Jae Woo Jung, Mingyu Kang, Ju-Young Kim, Ju-Young Kim, Hyun Jeong Kim, Yeon-Ju Woo, Soo-Youn Jung, Hye-Ryun Kang, Hye-Ryun Kang A504 Impact of Processes Certification on the Liability of Anti-Dust Mites Bed Covers Thierry Porée, Nabile Boukhettala, Emeline Furon A505 Localisation Kinetics of Aluminium after Subcutaneous Injection in a Rat Model Alan David Bullimore, Matthew Heath, Simon Hewings, Murray Skinner A506 Periostin Levels in Exhaled Breath Condensate of Competitive Athletes, Asthmatics and Healthy Subjects - Associations with Outdoor Ambient Conditions Marcin Kurowski, Hubert Krysztofiak, Aleksandra Wardzynska, Marzanna Jarzebska, Janusz Jurczyk, Marek L. Kowalski A507 The Role of PKR Pathway in Acute Exacerbation of Severe Bronchial Asthma So Ri Kim, Yong Chul Lee, Dong Im Kim, Yang Keun Rhee, Heung Bum Lee, Seoung Ju Park, Yeong Hun Choe Choe, Seung Yong Park A508 Diversity of Clinical Manifestations and Treatment Responses for Idiopathic Hypereosinophilic Syndrome Joo-Hee Kim, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A509 Effect of Dexamethasone in Th17 Cell Mediating Neutrophilic Asthma Nong Guang-Min, Jiang Min A510 Allergen Profile for Asthma/Rhinitis and Eczema Among Patients in North India: An Immunocap Allergen Specific IgE Antibodies Assay Based Study Nalin Nag A511 Clinical Profile of Allergic Rhinitis in Children in Jakarta Wahyuni Indawati A512 Preclinical Study on the Use of Micro Crystalline Tyrosine (MCT) Adjuvants in Allergy Immunotherapy Alan David Bullimore, Matthew Heath, Murray Skinner A513 Genetic Diversity of Filaggrin Mutation and Its Clinical Implication in East Asian Atopic Dermatitis Patients Seong Jun Seo, Won Jong Oh A514 Protein and MPL Adsorption Capacities for MCT in Candidate Therapeutic Formulations for Use in Immunotherapy, Compared Against Existing Adjuvants Alan David Bullimore, Murray Skinner, Matthew Heath, Andrew Bell A515 Interleukin-22 Gene Variation in Inflammatory Bowel Disease Alireza Zarebidoki, Hournaz Hasanzadeh, Salman Sadeghzade, Nima Rezaei A516 Immunomodulatory Effects of Adipose-Derived Stem Cell Secretome in a Mouse Model of Asthma Kyu-Sup Cho A517 Diffuse Alveolar Hemorrhage with Positive Anti-Neutrophil Cytoplasmic Antibody in a Child : A Case Report Sung-Woo Kim, Moo-Young Oh A518 Clinical Analys the Serum TARC Levels As the Condition Index of Atopic Dermatitis in the Early Infancy Munemitsu Koizumi, Kazuyo Kuzume A519 An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients Kui Young Park, Won Jong Oh A520 A New Protocol for Wheat Oral Immunotherapy in Patients with Anaphylaxis Delara Babaie, Mohammad Nabavi, Fariborz Zandieh, Mehrdad Amir Moini, Zahra Chavoshzadeh, Hamideh Seifi, Mitra Sahragard, Mehrnaz Mesdaghi, Mohammad Hassan Bemanian A521 Clinical Characteristics of Filaggrin-Related Atopic Dermatitis Patients in Korea Sun Young Choi, Yeon a No A522 Early Allergy Diagnosis in Children - Self- Administered Questionnaire Vs Medical Verification Andrzej M. Fal, Dorota Kiedik, Agnieszka Muszynska, Iwona Pirogowicz A523 Asthma Impact on Children with Food Induced Anaphylaxis Chikako Motomura, Masatoshi Wakatsuki, Yuko Akamine, Mihoko Iwata, Hiroshi Matsuzaki, Naohiko Taba, Yoko Murakami, Hiroshi Odajima A524 Case Reports of Stevens-Johnson Syndrome and Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis in Systemic Lupus Erythematosus Reni Ghrahani A525 The Effectiveness of Oral Tolerance Induction for Wheat Allergy Using Two Different Intake Levels Yuri Takaoka A526 Association of Plasma Interleukin-25 Levels with Development of Aspirin Induced Airway Spasm in Asthma Jong-Uk Lee, Jeong-Seok Heo, Da-Jeong Bae, Hyun Ji Song, Choon-Sik Park, Jong-Sook Park A527 Transition of Allergic and Nonallergic Rhinitis after 2 Years in Korean Children: Preliminary Study Jae Hoon Cho, Ji Ho Choi A528 Early Onset of Psoriasis Juvenile Idiopathic Arthritis Budi Setiabudiawan, Fiska Febriana, Reni Ghrahani, Gartika Sapartini A529 Clinical Features of Immediate Hypersensitivity to Histamine H2 Antagonists and Their Cross Reactivity Chan-Sun Park, Young-Hee Nam, Mi Yeoung Kim, Gil-Soon Choi A530 Detection of Galacto-Oligosaccharide Specific IgE in Vitro Chiung-Hui Huang, Chiung-Hui Huang, Jian Yi Soh, Lynette Shek, Lynette Shek, Dianne J. Delsing, Bee Wah Lee, Bee Wah Lee, Si Hui Goh, Wen Chin Chiang, Wenyin Loh A531 The Association Between Serum Vitamin D Levels and Allergic Diseases in Elementary Schoolchildren Hea-Kyoung Yang, Ji Young Lee, Minji Kim, Kangmo Ahn, Jihyun Kim, Young-Min Kim, Hye-Young Kim, Yong Mean Park, Woo Kyung KIM, So-Yeon Lee A532 Serum Levels Specific IgE to Toxic Shock Syndrome Toxin Type 1 in Eosinophilic Chronic Rhinosinusitis with Nasal Polyp in Korean Jongin Jeong, Sang Duk Hong, Seung Kyu Chung, Hun-Jong Dhong, Hyo Yeol Kim Hyo Yeol Kim, Sujin KIM A533 Impacts of Rhizosphere Cleaning Effects of Potted Indoor Plants on the Symptoms and Stress of Students with Allergic Rhinitis in Newly Built Schools Yong-Won Lee, Hana Bak, Hye-Rim Son, Si-Eun Lee, Kwang-Jin Kim, Young-Wook Lim, Ho-Hyun Kim A534 A Case of Multiple Food Allergies with Recurrent Anaphylaxis Successively Controlled By Omalizumab Mi-Ae Kim, Man Yong Han, Young-Ho Jung, Hye Mi Jee, Seung Jin Lee, Kyung Suk Lee A535 Bepotastine-Induced Urticaria, Cross-Reactive with Other Antihistamines Jasmina Golez, Jaechun Lee, Eunkyoung Lee A536 Role of SLC26a4 in Ozone - Induced Airway Reactivity and Inflammation Da-Jeong Bae, Chang-Gi Min, Jong-Uk Lee, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, An-Soo Jang A537 PAR2-Antagonist Suppresses Protease-Induced Allergic Inflammation Mediated By Degradation of Lung Epithelial Tight Junction and Generation of ROS Young-Joon Kim, Bok Kyoung Jung, Seung-Hwa Lee, Mi-Jin Kang, Sekyoo Jeong, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Song-I Yang, Seo Hee Kim, Soo-Jong Hong A538 Novel Anti-IL-4Ra Nanocarrier Approach for the Efficient Control of Lung Tissue Inflammation during Asthma Rabih Halwani, Saleh Al Muhsen, Asma Sultana, Achraf Al-Faraj, Rosan Kanana, Sibtain Afzal, Roaa Al Kufaidi A539 Clinical Factors for Improved Allergen Reactivities Induced By Subcutaneous Allergen Specific Immunotherapy with House Dust Mites during 1 Year Period Hee-Kyoo Kim, Chul-Ho Oak, Gil-Soon Choi, Ye-Jin Moon, Eun-Kee Park A540 Cytokine Gene Polymorphisms in Iranian Patients with Kidney Acute Rejection Alireza Zarebidoki, Mina Abrari, Ali Akbar Amirzargar A541 Phthalate Exposure and Obesity in Atopic Dermatitis of Korean Children and Adolescents Ju-Hee Seo, Mina Ha, Soo-Jong Hong A542 Which Drives Chronicity of Cough in Adults: Based on the Knhanes 2010-2012 Mingyu Kang, Byung-Ha Cho, Han-Ki Park, Han-Ki Park, Kyung-Mook Kim, Chang-Han Park, Heung Woo Park, Heung Woo Park, Yoon-Seok Chang, Yoon-Seok Chang, Yoon-Seok Chang, Sook-Hee Song, Mi-Kyeong Kim, Mi-Kyeong Kim, Sang-Heon Cho, Suk-Il Chang, Kyung-up Min, Kyung-up Min, Alyn Morice A543 Elevated Airway CD45RO Memory Cells in Wheezing Children with Lower Respiratory Infection Jungi Choi, Yusok Han, Jin-Sung Park, Eunmi Kwon, Chang-Keun Kim A544 Quality of Life in Obese Children with or without Atopic Disease Gartika Sapartini A545 Relation of Human microRNA in Sputum of Asthma with Influenza A Virus Infection-Induced Exacerbation Ji-Na Kim, Seungwoo Shin, Hun Soo Chang, Eun-Young Shim, Ji Ah Jun, Hyeonju Lee, Jong-Sook Park, Choon-Sik Park A546 Aeropolinologic Monitoring and Distribution of Allergoallergens in Western Georgia Revaz Sepiashvili, Darejan Khachapuridze, Sofio Gamkrelidze, Manana Chikhladze A547 Extracorporeal Membrane Oxygenation As Emergency Treatment for Patients with Near-Fatal Status Asthmaticus Seung-Eun Lee, Yun-Seong Kim, Doo-Soo Jeon, Woo-Hyun Cho, Hye-Ju Yeo, Seong-Hoon Yoon, Seung-Hyun Kim A548 Relationship of S100calcium Binding Protein A9 with Neutophilic Inflammation in Murine Asthma Model Taehyeong Lee, Hyun Ji Song, Choon-Sik Park, Ji Ah Jun, Jong-Sook Park A549 Whole-Exome Sequencing of Aatopic Dermatitis in Korean Childhood Dankyu Yoon, Yeon-Seop Kim, Woo-Sung Chang, Mi-Jin Kang, Soo-Jong Hong, Jeom-Kyu Lee, Eun-Jin Kim A550 A Case of Generalized Molluscum Contagiosum in an Adult Patient with Severe Atopic Dermatitis Minkee Park A551 Discovery of Putative Macadamia Nut Allergens By Patient IgE Binding and a Label-Free Shotgun Proteomics Approach Nanju Alice Lee, Johanna Rost, Sridevi Muralidharan, Dianne Campbell, Sam Mehr A552 Anti-FcÎμri Antibody Inhibits Allergic March in Mice By Suppressing Th17 Pathway Via Suppression of FcÎμri-Mediated Mast Cells Activation Seung-Hwa Lee, Seon-Joo Yoon, Ha-Jung Kim, Eun Lee, Song-I Yang, Young-Ho Jung, Ho-Sung Yu, Hee-Suk Kim, Yeon Hee Park, So-Yeon Lee, Jun-Sung Park A553 Clinical Characteristics and the Associated Factors of ATG Hypersensitivity Reaction Ha Kyeong Won, Min-Koo Kang, Sung Do Moon, Byung-Keun Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Ji-Su Shim, Soo Jie Chung A554 Reference Value and Utility of Total Serum Immunoglobulin E in Korean Schoolchildren Jaehee Choi, Kangmo Ahn, Kwanghoon Kim, Jihyun Kim, Jiyoung Lee A555 Two-Step Prescreening Skin Testing May be Useful for Reducing Immediate Hypersensitivity Reaction to Nonionic Contrast Media: Results of 7-Year Period in a Secondary Hospital Bo Bae Park, In Young Nho, Chang-Han Park, Jang Min Kim, Suk-Il Chang A556 Prevalence of Allergic Sensitization in Patients with Allergy Rhinitis; Gwangju, Jeonnam State Study Sun Kyung Kim, Hyung Chae Yang, Kwang Il Nam A557 Analysis of IgE Binding Components of Walnut in Korean Children Effect of Cooking Methods on the Allergenicity of Walnut Proteins Jeongmin Lee, Jeongmin Lee, Sooyoung Lee, Kyunguk Jeong, Se-Ah Jeon A558 Assessment of Autonomic Nervous Function in Subjects with Cholinergic Urticaria Associated with Acquired Idiopathic Generalized Anhidrosis Midori Fujiwara, Shoko Shindo, Hiroyuki Murota, Mayuko Tahara, Aya Takahashi, Ichiro Katayama A559 Interleukin 1 Beta in Sputum of Patients with Asthma: Relation with Airway Obstruction and Neutrophilc Inflammation Jae Woo Jung, Hyun Ji Song, Taehyeong Lee, An-Soo Jang, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, Byoung Whui Choi A560 Interleukin 8 in Sputum of Patients with Asthma: Relation with Neutrophilc Inflammation and Exacerbation Min-Hye Kim, Da-Jeong Bae, Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Jong-Sook Park, An-Soo Jang, Hun Soo Chang, Young Joo Cho, Choon-Sik Park A561 Prostaglandin E2 and Transforming Growth Factor-Î(2) Play a Critical Role in Suppression of Allergic Airway Inflammation By Adipose-Derived Stem Cells Sue Jean Mun A562 Inhalation of Fine Particles Kill Alveolar Macrophages to Release IL-1alpha That Promote Inducible Bronchus-Associated Lymphoid Tissue (iBALT) Formation Etsushi Kuroda, Koji Ozasa, Ken Ishii A563 Association Between Smoking and Allergic Diseases in the Korean Adult General Population Sunmi Kim, Gyeong-Hun Park A564 Relationship of S100 Calcium Binding Protein A9 with Inflammasome Activation in Murine Asthma Model Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Hun Soo Chang, Jong-Sook Park, Choon-Sik Park A565 Cluster Analysis of Asthma Phenotypes to Predict Exacerbation in Korean Population Mi-Ae Kim, Seungwoo Shin, Jong-Sook Park, Hun Soo Chang, You Sook Cho, Hae-Sim Park, Choon-Sik Park A566 Effect of AG490 on the Expression of TH17 CELLS and Tregs in the MOUSE MODEL of Neutrophilic Asthma Zhang Min A567 Association Between the Clinical Characteristics and Disease Severity in Hospitalized Bronchiolitis Patients Younger Than Two Years Old Seo Hee Yoon, In Suk Sol, Young a Park, Yoon Hee Kim, Min Jung Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A568 Comparison Between House Dust Mite and Aspergillosis Sensitization in Patients with High Level of Tige Wu Shiquan A569 The Prevalence of Metal Allergy in the Patients with Orthodontic Appliance Yongwon Lee, Hana Bak A570 Component Resolved Diagnosis and Single Nucleotide Polymorphism Analyses: Towards the Development of Specific Immunotherapy for Allergy Maricar Wisco Ching, John Donnie Ramos A571 Clinical Features of Anaphylaxis Caused By Peanut, Tree Nuts and Seeds in Children and Adolescents: Multi-Center Study with 126 Patients Kyunguk Jeong, Sooyoung Lee, Kangmo Ahn, Myung Hyun Sohn, Kyung Won Kim, So-Yeon Lee, Tae Won Song, Youhoon Jeon, Jihyun Kim, Taek Ki Min, Kyu-Earn Kim, Bok-Yang Pyun, Hyeon-Jong Yang, Hae Ran Lee, Youngmin Ahn, Ji-Won Kwon, Dae Hyun Lim, Jeong Hee Kim, Dongin Suh, Hyung Young Ki A572 A Report of Two Cases of Anaphylaxis Caused By Perilla Seed in Children Kyunguk Jeong, Byeong Sub Park, Sooyoung Lee, Se-Ah Jeon, Kyu Jung Park A573 Prenatal Fine Particulate Matter Affects Wheezing in Children with TLR4 Polymorphism: Cocoa Study Song-I Yang, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Mi-Jin Kang, Yean Jung Choi, Kil Yong Choi, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Byoung-Ju Kim, So-Yeon Lee, Eun-Jin K A574 Intensified B Lymphocyte Depletion (IBLD) without Immunosuppressive Maintenance Treatment As a Rescue Therapy in Refractory Lupus Nephritis (LN): a 4-Year Observation. Roccatello Dario A575 Relationship Between Th17 Cells and Neutrophilic Airway Inflammation in Childhood Neutrophilic Asthma Jing Liao A576 Clinical Applications of Impulse Oscillometry in Asthma Management after Exacerbation in Preschool Children Yong Feng, Yunxiao Shang A577 Contact Allergy to Sodium Sulfite and Its Relationship to Facial Cosmetic Contact Dermatitis Yongwon Lee, Hana Bak A578 Effect of Exposure to Air Pollution on Asthma and Lung Function Development Hyung Young Kim, Byoung-Ju Kim, Ji-Won Kwon, Ju-Hee Seo, Eun Lee, So-Yeon Lee, Song-I Yang, Young-Ho Jung, Hyo-Bin Kim, Ho-Jang Kwon, Hee Ju Park A579 Role and Relational Mechanism of AG490 in Airwayinflammation in the Mouse Model of Neutrophilic Asthma Zhang Min, Nong Guang-Min, Jiang Min A580 Incidence of Adverse Reaction to Radioconstrast Media in a Single Tertiary Hospital Gyu Young Hur, Eun Jung Sim, Sora Yoon, Juwhan Choi, Junga Kim, Jae Keom Sim, Jee Youn Oh A581 Cow’s Milk Oral Food Challenge: Clinical and Laboratory Features in Korean Children Kyunguk Jeong, Byeong Sub Park, Jeong-Min Lee, Sooyoung Lee, Eunjae Cheon, Youngjoo Na, Kyu Jung Park, Eunjoo Lee A582 Validation of the Red Maple Trials Allergen Challenge Theatre for Ragweed Pollen Challenge William Yang, Suzanne Kelly, Rob Perrins, Jimmy Yang A583 Preliminary Evaluation of the Red Maple Trials Allergen Challenge Theatre for Grass Pollen William Yang, Suzanne Kelly, Rob Perrins, Jacob Karsh, Jimmy Yang A584 The Association Between Tobacco and the Risk of Asthma in Urban and Rural Children in San Francisco, Argentina Hector Badellino, Alvaro Teijeiro, Mabel Cuello, Marilyn Urrutia Pereira, Gustavo Egues A585 The Prevalence of Allergic Rhinitis in University Students in Manisa Ayse Aktas A586 Allergen Sensitization in Zimbabwean Children with Atopic Dermatitis Jin-Kyong Chun, Hilda Angela Mujuru, Elopy N Sibanda A587 Vitamin D Insufficiency in Asthmatic Patients Andreea Ioana Popescu, Raluca Greblescu A588 The Prevalence of Hypersensitivity Reactions Against Drugs Among University Students. Suheyla Rahman, Ayse Aktas A589 Sublingual Immunotherapy Among Problematic Patients, Suffering from Allergic Rhinitis. Nataly Tataurshchikova A590 A Novel Biomarker for Wheezing and Atopy in Early Infancy Eishika Dissanayake, Yuzaburo Inoue, Naoki Shimojo, Taiji Nakano A591 Prognostic Factors for Atopic Dermatitis in Spontaneously Born Babies from Low Socioeconomic Background Conny Tanjung A592 Higher IgE Antibody Levels Mediate Anti-Cancer Immunity in Transgenic KN1 Hyper-IgE Mice Erika Jensen-Jarolim, Judit Fazekas, Josef Singer, Anna Lukschal, Reinhard Horvat, Gertrude Achatz-Straussberger, Gernot Achatz A593 Fructooligosaccharides Intake during Pregnancy and Lactation Increases Gut Bifidobacterium and IL-27 in Breast Milk Yuji Fujita, Shuji Ikegami, Yoshitaka Nakamura, Yuzaburo Inoue, Naoki Shimojo, Yoichi Kohno, Shuichi Suzuki, Naoko Ozawa, Takayuki Kubota, Ken Nonaka, Osamu Ohara, Kentaro Masuda A594 Effect of Nintedanib on Asthma in Mouse Model Chin Kook Rhee, Sook Young Lee, Hwa Young Lee, Hea Yon Lee, Ji Young Kang, Sei Won Kim, Soon Seog Kwon, Young Kyoon Kim A595 Delayed Contrast Media Hypersensitivity after Coronary Angiography Gun-Woo Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Hyo-Soo Kim, Jung Gyu Han, Jin Lee, Ji Young Lee, Ji Young Go, So Jung Park A596 Gene Expression Profiling in Patients with Chronic Idiopathic Urticaria Reveals Unique Gene Signature Distinct from Healthy Controls Julie Kim-Chang, Cassandra Love, Patricia Lugar A597 Failure to Recognize Lymphopenia in Newborn Leads to Undetectable Primary Immunodeficiency Endah Citraresmi A598 The Concordance Between Lung Function Test and Indonesian Version of Childhood Asthma Control Test (CACT) Nastiti Kaswandani, Cynthia Utami, Mardjanis Said A599 Synergistic Interaction Between Bronchiolitis and PM(10) Is Modified By IL-13 Polymorphism on Asthma Development: Replication from Cheer Study Young-Ho Jung, Song-I Yang, Byoung-Ju Kim, Ji-Won Kwon, Hwan-Cheol Kim, Jong-Han Leem, Ju-Hee Seo, Hyung Young Kim, So-Yeon Lee, Ho-Jang Kwon, Hyo-Bin Kim, Hyun-Ju Cho A600 The Transcription Factor Ehf Is Involved in TGF-b-Induced Suppression of Fceri and c-Kit Expression and Fceri-Mediated Activation in Mast Cells Susumu Yamazaki, Nobuhiro Nakano, Asuka Honjoh, Eisuke Inage, Yosuke Baba, Yoshikazu Ohtsuka, Toshiaki Shimizu A601 The Follow up of the Potential Immunosuppressant Effects of Marijuana (MJA) Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A602 Risk Factors of Allergen Sensitization at 3 Years: Results from the Gusto Study Evelyn Xiu Ling Loo, Anne Goh, Oon Hoe Teoh, Yiong Huak Chan, Seang Mei Saw, Kenneth Kwek, Peter D Gluckman, Keith M Godfrey, Hugo Van Bever, Yap Seng Chong, Bee Wah Lee, Lynette Shek, Alison Joanne Lee A603 IL-6 Blockade As a Steroid-Sparing Treatment for Rhupus Patients Daniela Rossi A604 Examination of Late Pulmonary Toxicity in Children Treated for Malignancies Agnes Nemeth A605 Technical Validation of the Repurposing of a Personal Particle Sampler to Determine House Dust Mite Exposure in the Ambient Air Torsten Sehlinger, Karl-Christian Bergmann, Frank Goergen A606 Zinc Deficiency in Children with Severe Atopic Dermatitis: More Common Than Generally Thought Mohammad S. Ehlayel, Abdul Bari Bener A607 Strong Association Between HLA-B*5801 Allele and Allopurinol – Induced Severe Cutaneous Adverse Reactions in Vietnamese Hieu Chi Chu, Nga Thi Quynh Do, Dinh Van Nguyen, Ha Thi Thu Nguyen, Huong Thi Minh Le, Sheryl Van Nunen, Christopher Vidal, Suran Fernando A608 Successful Rapid Desensitization to Glatiramer Acetate: Report of 2 Cases Fotis Psarros, Ekaterini Syrigou, Ekaterini Politi, Spyridon Chrysoulakis A609 Asthma Exacerbations Seasonal Variation in Two Perennial Phenotypes during Twenty Years (1995-2014): House Dust Mite Monosensitized and Non Atopic Patients Dimitrios Vourdas, Konstantinos Petalas A610 Occupational Allergy to Fungal Spores Among the Farmers of Paddy Fields in West Bengal, India: An Aeromycological and Immunological Approach Mouli SAHA, Kashinath Bhattacharya A611 Study of Efficacy of Sublingual Immunotherapy (SLIT) in Cases of Severe Persistent Allergic Rhinitis Subir Jain A612 Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Pathway Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Xiaolian Song, Haiyan Lin A613 Development of Allergen ELISA Kits for Dust Mites, Pollen, and Pet Dander Kyohei Nishikawa, Takashi Shimada, Hiroshi Yasueda, Tadao Enomoto, Daisuke Aizawa, Takayoshi Kobayashi A614 Yoga As a Lifestyle Modification to Improve the Quality of Life in Smokers with Allergic Rhinitis Chellaa R A615 Study of Incidence of Severe Persistent Allergic Rhinitis in Different Age Groups,Sex Prevalance and Type of Allergen” Aeroallergen or Food Allergen” Responsible for Severe Persistent Allergic Rhinitis in Central India Subir Jain A616 Causative Allergens in Cases of Severe Persistent Allergic Rhinitis in Central India Subir Jain A617 Atopic Dermatitis: A New Data on the Mechanisms of Chronic Pruritus Marina Yudina A618 The Efficacy and Safety of Peanut Oral Immunotherapy in High-Dose with Predicting Factors Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A619 Evaluation of Long-Term Prognosis and Topical Corticosteroid Usage after One Year of Proactive Treatment for Children with Moderate-to-Severe Atopic Dermatitis Mayako Saito A620 Allergy Symptoms in the First Two Months of Life Nurul Iman Nilam Sari A621 Factors Related to the Seasonal Variation of Allergic Rhinitis Jae Young Kim, Jaechul Song, Inah Kim, Kyeong Joon Lee, Soo Jin Park, Soo Yong Roh A622 Allergic Risk Survey in Lao Children at out-Patient Department, Children’s Hospital, Vientiane Capital, Lao PDR Somxay Billamay A623 Correlation Between Food Allergy, Aeroinhalant Allergy, Allergic Rhinitis, Atopic Dermatitis, and Acute Upper Respiratory Tract Infections and Levels of Severity of Asthma in Pediatric Medicine Department Saiful Anwar Hospital Indonesia Muchammad Fahrul Udin A624 Comparative Study of Pine, Oak, and Ginkgo Pollen Counts in Korea during Last Four Years Mae Ja Han, Jae-Won Oh, Kyu Rang Kim, Baek-Jo Kim A625 Effectiveness of Allergy-Test Directed Elimination Diets in Eosinophilic Esophagitis Jorge A Mazza, Jason Kangeun Ko, David JT Huang A626 Comparison of Cut-Off Values and Probability Curves for Egg Specific IgE in Diagnosis of Egg Allergy in Young Children Kanae Furuya, Keigo Kainuma, Takahiro Ito, Mizuho Nagao, Takao Fujisawa, Junya Hirayama, Yu Kuwahara A627 A Case of Persistent Atopic Dermatitis Associated with Parasitic Infection Rosanna Qualizza, Cristoforo Incorvaia, Anna Maraschini A628 Aeroallergenic Profile of Indoor Allergens and Their Clinical Relevance in Allergy and Asthma Patients in Saudi Arabia Syed Mohammed Hasnain, Abdulrahman Al-Frayh A629 Oral Exposure to the Amino Acid Glycine Inhibits the Onset of Allergic Disorders Anita Hartog, Jacqueline Bastiaans, Reinilde Loonstra, Lieke Rutten, Lucien Harthoorn, Jeroen Van Bergenhenegouwen, Johan Garssen, Johan Garssen A630 Cough As a Key Symptom in Asthma, Allergic Rhinitis, COPD and Rhinosinusitis and Its Impact in Korea Kwang-Ha Yoo, Sang-Heon Cho, AG Ghoshal, Abdul Razak Bin Abdul Muttalif, Horng- Chyuan Lin, Sanguansak Thanaviratananich, Shalini Bagga, Rab Faruqi, Santwona Baidya, Colman Taylor, De Yun Wang, Hae-Ryun Ahn, Soon-Kwan Hong, Jong-Woong Kim, Gui-Hyun Nam, Mee-Ja Kim, Jae-Kyoung Park A631 Cysteine Protease Allergen Def f 1 Induces Th2 Cytokines in Mouse Bone Marrow Derived Basophils Via ERK and JNK Dependent Pathways Myung-Hee Yi, Kyoung Yong Jeong, Ju-Yeong Kim, Tai-Soon Yong A632 Novel Multiple Allergy Testing Kit Using Parallel Lines Array (PLA) Technology Bum Joon Kim, Hs Joo, Kj Lim, Jae-Hyun Lee, Jung-Won Park, Kh Yoon, DS Choi A633 Quantitative Rapid Kit for Human Immunoglobulin Hanseung Joo, Bum Joon Kim, Kj Lim, MJ KIM, DS Choi, Kh Yoon A634 Total IgE Measurement By Protia Allergy-Q: Comparison Study with Immunocap Bum Joon Kim, Hanseung Joo, Woo Sang Jung, Kj Lim, DS Choi A635 Prevalence and Risk Factors of Asthma Among Korean Farmers Ji-Hoon Lee, Soon-Chan Kwon, Soo-Jin Lee, Soo Yong Roh, Hogil Kim, Kyeong Joon Lee A636 Dietary Intake and Perceived Immune Status in Young Dutch Women Aurora Van De Loo, Amanda Fernstrand, Johan Garssen, Joris Verster A637 The Effects of Antihistamine Drugs on on-Road Driving Performance Aurora Van De Loo, Johan Garssen, Joris Verster A638 Grass Is Guilty: A Case of Anaphylactic Shock and Asthmatic Status in the Same Time in an Individual Jasmina Golez A639 Cyclic Gamp-AMP(cGAMP) Induces Allergic Inflammation Koji Ozasa, Etsushi Kuroda, Ken Ishii, Ken Ishii A640 Role of Omalizumab in the Setting of Recalcitrate Dermatitis with Extremely Elevated IgE Levels Muhammad Imran, Selina Gierer, John Martinez A641 Follow-up Study on the Natural History of Prawn Allergy Lydia Wong, Bee Wah Lee, Gaik Chin Yap, Genevieve Llanora, Bernard Thong, Lynette Shek A642 Protein-Losing Dermopathy Impairing Growth in Children with Severe Atopic Dermatitis Mohammad S. Ehlayel, Ashraf Soliman A643 Airways Assessment of Aged Nursing Homes Residents Pedro Martins, João Marques, Joana Gomes-Belo, Teresa Palmeiro, Iolanda Caires, Joana Belo, Maria Amália Botelho, Paula Leiria-Pinto, Nuno Neuparth A644 Use of Skin Prick Test, Specific IgE to Shrimp and Rpen a1 to Determine Clinical Reaction to Shrimp in Area with High Prevalence of House Dust Mite Sensitization Narissara Suratannon, Jaichat Mekaroonkamol, Jarungchit Ngamphaiboon, Piyawadee Lertchanaruengrith, Pantipa Chatchatee A645 Identification of Specific IgE-Binding Proteins in Tree of Heaven (Ailanthus altissima) Pollen Gholamali Kardar, Ahmad Majd, Youcef Shahali, Farrokh Ghahremaninejad, Zahra Pourpak, Fateme Mousavi A646 Allergy Immunotherapy Well Tolerated in Children Mahnaz Sadeghi-Shabestari A647 Steinert (DM1) Patients Have IgG1 Deficiency and Should be Screened for Immune Deficiency K. Van Bilsen, O. Manusama, W.a. Dik, M. Van Der Burg, V. H. J. Van Der Velden, V.a.S. H. Dalm, P. M. Van Hagen A648 The Change of Serous Sige and Three Evaluation before and after Sublingual Immunotherapy with Dermatophagoides Farinae for Persistent Allergic Rhinitis Yongping Liu A649 Garlic Extracts Reduce Histamine-Induced Proliferation and Migration of Human Asthmatic Bronchial Smooth Muscle Cells Yi Yeong Jeong A650 A Case of Occupational Contact Dermatitis Caused By N-Acetylcysteine Ji Hye Kim, Moon Gyeong Yoon, Young Min Ye, Yoo Seob Shin, Ga Young Ban, Hae-Sim Park, Hye Min Jung A651 The Association Between Pollen Change and Asthma Attacks Soo Yong Roh, Jaechul Song, Ji-Hoon Lee, Hogil Kim, Jae Young Kim, Kyeong Joon Lee A652 Incidence of Emergency Department Visits and Hospitalizations for Asthma Exacerbations during the Lunar Month in Singapore Lydia Wong, Mohana Rajakulendran, Haripriya Santhanam, Lynette Shek, Tow Keang Lim A653 The Prevalence of Positive Reaction for Skin Prick Test in Korean Farmers and Its Occupational Risk Factors Hogil Kim, Soo-Jin Lee, Ji-Hoon Lee, Soo Yong Roh, Soon-Chan Kwon A654 Drug Allergy in Children: A Three-Years Experience at Dr. Kariadi Hospital Semarang Indonesia Wistiani, Galuh H, Ani Wistiani A655 The Identification of Morphology, Structure and Study of Seasonal Variation of Airborne Fraxinus Excelsior Pollen Grains in the Tehran Gholam Ali Kardar, Maryam Sharifshoushtari, Ahmad Majd, Taher Nejadsattari, Zahra Pourpak, Mostafa Moin A656 Sublingual Immunotherapy in Elderly Rhinitis Patients Sensitized to House Dust Mites Ji Hye Kim, Daehong Seo, Young Min Ye, Hae-Sim Park, Jung-Won Park, Jae-Hyun Lee, Yoo Seob Shin A657 Healthy Ageing Research Center (HARC) As a Platform for Multidisciplinary Approaches to Respiratory Research in the Elderly Marek L. Kowalski, Aleksandra Wardzynska, Marcin Kurowski, Malgorzata / Ewa Pawelczyk, Adam Wysokinski, Iwona Kloszewska, Janina Grzegorczyk, Wojciech Piotrowski, Joanna Makowska A658 Estimation of Cases of Work-Related Asthma Using Capture-Recapture Methods Soon-Chan Kwon, Jaechul Song, Yong-Kyu Kim A659 Primary School Students’ Parents Reported ISAAC Questionnaire in a Low Income Area of Ankara Ilknur Bostanci, Zeynep Sengul Emeksiz, Aysegul Ertugrul, Serap Ozmen, Soner Sahin A660 Usefulness of PC20 Adenosine Monophosphate in Diagnosis and Treatment in Bronchial Asthma Sang-Ha Kim, Myoung Kyu Lee, Won Yeon Lee, Suk Joong Yong, Seok Jeong Lee, Ye-Ryung Jung A661 S100 Calcium Binding Protein A9 in Sputum of Patients with Steroid Naive Asthma: Relation with Airway Obstruction and Nneutrophilc Inflammation Myung Shin Kim, Jong-Sook Park, An-Soo Jang, Choon-Sik Park A662 Risk Factor Asthma in Pediatric Pneumonia Patients Diah Asri Wulandari, Cissy Kartasasmita A663 Prevalence and Risk Factors of Childhood Asthma and Allergic Disease at Exposed Area By Emission of Cement Padang Factory Finny Fitry Yani, Rizanda Machmud, Dhina Lydia Lestari A664 Association Between Serum Level of 25-Hydroxyvitamin D with Atopic Dermatitis Occurrence and Severity in Children Rusdi Rusdi, Yurmalina Yurmalina, Eryati Darwin A665 Thiol-Disulfide Balance in Children with Atopic Dermatitis Ilknur Bostanci, Gulin Karacan, Nazli Ercan, Asuman Colak, Murat Alisik, Gulay Basarir, Ozcan Erel A666 Recurrent Mouth Ulsers Caused By Braces after Developing a Nickel Allergy in Children Ilknur Bostanci, Yasemin Keskin A667 Anaphylactic Reaction to Famotidine with Pheniramine Hypersensitivity Ilkay Koca Kalkan A668 Novel Transcriptomic and Immunoproteotomic Approaches in Identifying Cross-Reactive Allergens Between Crustacean and Molluscs Andreas/Ludwig Lopata, Kyall Zenger, Roni Nugraha, Sandip Kamath A669 Pollen Season and Climate Change in the Continental United States (CONUS) Leonard Bielory, Panos Georgopoulos, Yong Zhang, Wheat Mi, Ting Cai A670 Differences of Change in Der p IgG4 and CD4+CD25+FoxP3+ Treg Cells Between Sublingual and Subcutaneous Immunotherapy with House Dust Mite in Chinese Patients with Allergic Rhinitis MO Xian, Jing Li, Mulin Feng

negative: Naturally occurring mutations in PB1 affect influenza A virus replication fidelity, virulence, and adaptability BACKGROUND: Mutations in the PB1 subunit of RNA-dependent RNA polymerase (RdRp) of influenza A virus can affect replication fidelity. Before the influenza A/H1N1 pandemic in 2009, most human influenza A/H1N1 viruses contained the avian-associated residue, serine, at position 216 in PB1. However, near the onset of the 2009 pandemic, human viruses began to acquire the mammalian-associated residue, glycine, at PB1–216, and PB1–216G became predominant in human viruses thereafter. METHODS: Using entropy-based analysis algorithm, we have previously identified several host-specific amino-acid signatures that separated avian and swine viruses from human influenza viruses. The presence of these host-specific signatures in human influenza A/H1N1 viruses suggested that these mutations were the result of adaptive genetic evolution that enabled these influenza viruses to circumvent host barriers, which resulted in cross-species transmission. We investigated the biological impact of this natural avian-to-mammalian signature substitution at PB1–216 in human influenza A/H1N1 viruses. RESULTS: We found that PB1–216G viruses had greater mutation potential, and were more sensitive to ribavirin than PB1–216S viruses. In oseltamivir-treated HEK293 cells, PB1–216G viruses generated mutations in viral neuraminidase at a higher rate than PB1–216S viruses. By contrast, PB1–216S viruses were more virulent in mice than PB1–216G viruses. These results suggest that the PB1-S216G substitution enhances viral epidemiological fitness by increasing the frequency of adaptive mutations in human influenza A/H1N1 viruses. CONCLUSIONS: Our results thus suggest that the increased adaptability and epidemiological fitness of naturally arising human PB1–216G viruses, which have a canonical low-fidelity replicase, were the biological mechanisms underlying the replacement of PB1–216S viruses with a high-fidelity replicase following the emergence of pdmH1N1. We think that continued surveillance of such naturally occurring PB1–216 variants among others is warranted to assess the potential impact of changes in RdRp fidelity on the adaptability and epidemiological fitness of human A/H1N1 influenza viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-019-0547-4) contains supplementary material, which is available to authorized users.

negative: COVID-19: A Risk Assessment Perspective [Image: see text] COVID-19 is a newly emerging viral respiratory disease first identified in Wuhan, China, in December 2019. The disease is caused by the coronavirus SARS-CoV-2, which is related to the viruses that cause SARS and MERS. While the case fatality ratio for COVID-19 (5%) is far lower than that for SARS (11%) and MERS (34%), COVID-19 is spreading relatively uncontrolled at this time across the globe. In contrast, SARS appears to be contained, and MERS is controlled. This paper will explore why COVID-19 is able to progress to a global pandemic that affects our daily lives to an extent not known in recent history. The COVID-19 outbreak and spread will be examined based on the current literature, using a researcher’s perspective of risk assessment and risk mitigation; this approach will be related to public health.

negative: Preventive behaviors, beliefs, and anxieties in relation to the swine flu outbreak among college students aged 18–24 years AIM: The objective of this study was to assess beliefs, misconception, and anxiety in relation to swine flu outbreak and whether perception of the outbreak predicted changes in behavior. SUBJECT AND METHODS: In November 2009, we conducted an Internet-based cross-sectional survey of college students aged 18–24 years in a Midwestern State in the USA. We collected information on swine flu knowledge, perception on immunization safety, perceived efficacy of recommended behavior, changed behavior, and anxiety. RESULTS: Of the 236 respondents, 83.1% had some anxiety about swine flu, 64.8% believed avoiding crowded places was preventive, 33.5% believed the 2009 swine flu vaccine was safe, and 36.9% showed interest in receiving the vaccine. Misconceptions about swine flu contagion via eating cooked pork, water sources, and insect bites were common. Respondents were unaware of transmissions via contaminated objects and droplets. Only 42.6% were satisfied with governmental efforts. Women were more likely to wash hands frequently than men (odds ratio 2.80, p < 0.001). CONCLUSION: There is a gap in swine flu knowledge, minimal risk reduction, increased amount of anxiety, and skepticism about swine flu vaccine safety. These gaps warrant serious attention to inform the public about specific actions regarding swine flu.

negative: Avian influenza surveillance in domestic waterfowl and environment of live bird markets in Bangladesh, 2007–2012 Avian influenza viruses, including highly pathogenic strains, pose severe economic, animal and public health concerns. We implemented live bird market surveillance in Bangladesh to identify the subtypes of avian influenza A viruses in domestic waterfowl and market environments. We collected waterfowl samples monthly from 4 rural sites from 2007 to 2012 and environmental samples from 4 rural and 16 urban sites from 2009 to 2012. Samples were tested through real-time RT-PCR, virus culture, and sequencing to detect and characterize avian influenza A viruses. Among 4,308 waterfowl tested, 191 (4.4%) were positive for avian influenza A virus, including 74 (1.9%) avian influenza A/H5 subtype. The majority (99%, n = 73) of the influenza A/H5-positive samples were from healthy appearing waterfowl. Multiple subtypes, including H1N1, H1N3, H3N2, H3N6, H3N8, H4N1, H4N2, H4N6, H5N1 (clades 2.2.2, 2.3.2.1a, 2.3.4.2), H5N2, H6N1, H7N9, H9N2, H11N2 and H11N3, H11N6 were detected in waterfowl and environmental samples. Environmental samples tested positive for influenza A viruses throughout the year. Avian influenza viruses, including H5N1 and H9N2 subtypes were also identified in backyard and small-scale raised poultry. Live bird markets could be high-risk sites for harboring the viruses and have the potential to infect naive birds and humans exposed to them.

negative: Characteristics of Australian human enteric coronavirus-like particles: comparison with human respiratory coronavirus 229E and duodenal brush border vesicles The polypeptide profiles of highly purified coronavirus-like particles (CVLPs) proved to be very different from that of human respiratory coronavirus 229E and showed the particles not to be coronaviruses. Differences in polypeptide profiles and morphology between the CVLPs and duodenal brush border vesicles suggested that the CVLPs were also not such vesicles. Although they shared some basic overall similarity, the polypeptide profiles of three different but possibly antigenically identical CVLP preparations from Central Australian Aborigines were very dissimilar in detail. At least 38, 39 and 48 bands respectively were observed on the three profiles. At least 46 bands were visible on the polypeptide profile of CVLPs from a Vietnamese immigrant to Australia, and it also differed in detail from those of the Central Australian CVLPs. Indications of antigenic difference were obtained between Central Australian CVLPs and CVLPs from India, Kiribati, South Africa and Vietnamese immigrants to Australia. Antigenic difference was also suggested between the Central Australian CVLPs and those from one distant location within Australia, but antigenic similarity with those from another was indicated.

negative: Hospital-based surveillance of influenza A(H1N1)pdm09 virus in Saudi Arabia, 2010-2016 BACKGROUND: Influenza is a highly contagious acute viral respiratory tract infection. The emergence of influenza A(H1N1)pdm09 in 2009 caused a pandemic. Since then it has become a seasonal influenza virus. It causes symptoms ranging from mild to severe illness, which might be fatal, particularly in people with underlying chronic medical conditions, immunocompromised people, the elderly, and pregnant women. OBJECTIVE: Describe the data generated by the influenza A(H1N1) pdm09 surveillance in Saudi Arabia from 2010 to 2016. DESIGN: Retrospective, descriptive. SETTING: Hospitals reporting to the Ministry of Health. MATERIALS AND METHODS: We studied aggregate data on hospitalized cases of influenza A(H1N1)pdm09 in Saudi Arabia between 2010 and 2016. The surveillance system used the case definition proposed by the WHO. The cases were confirmed by performing the real-time PCR (polymerase chain reaction) on upper respiratory samples. MAIN OUTCOME MEASURES: Suspected and confirmed influenza A(H1N1)pdm09 cases. SAMPLE SIZE: 113 502 suspected H1N1 cases and 17 094 (15.1%) confirmed cases. RESULTS: Most of the reported cases were registered in the Riyadh region. During the period of the study, the highest number of confirmed cases, 9262 (54.2 %), was in 2015. The case fatality rate for confirmed cases was 3.6%. CONCLUSION: Influenza A(H1N1)pdm09 showed seasonal trends. The number of suspected influenza cases each year was proportionate to the number of confirmed cases for that year. Riyadh, Jeddah and the Eastern areas (regions with the highest population) reported most of the cases. LIMITATION: Only one strain of H1N1 was tested. CONFLICT OF INTEREST: None.

negative: An overview of coronaviruses including the SARS-2 coronavirus – Molecular biology, epidemiology and clinical implications Abstract Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.

negative: [Case report of the first world death due to a new strain of human influenza A H1N1 virus and behavior of human influenzae in pregnant women]. Influenza A H1N1 is an acute respiratory illness caused by a new strain of H1N1. Human influenza is a subtype of influenza Avirus, from the family of Orthomyxoviridae. This strain is the cause of new influenza pandemic declared by the World Health Organization in June, 2009. This paper reports the first case occurred in Mexico: a 39-year-old woman with a history of diabetes mellitus type 2 and obesity grade II, which suffered atypical and aggressive pneumonia positive to coronavirus. Patient died 98 hours after her admission to the hospital unit. Due to the clinical presentation of the case, the doctors sent samples to the Instituto Nacional de Diagnóstico y Referencia Epidemiológica that sent an aliquot of the National Center for Immunization and Respiratory Diseases of theAgency of Public Health in Canada, that reported positivity to influenza virus, and catalogued it as a new global strain called influenza A virus H1N1. The notice of 229E/NL63 coronavirus and its relationship to the recent outbreaks of avian influenza in humans and the clinical presentation of the case were the epidemiological circumstances that prevented the nation epidemiology system to establish global containment strategies to prevent the spread of this emerging infection. The consequence was the declaration of WHO pandemic alert level 6. Its behavior in pregnancy, reported by Assistant General Direction of Epidemiology in Mexico, has placed this infection as a risk factor for women.

negative: Glycoproteins and their relationship to human disease. Glycoproteins are proteins that carry N- and O-glycosidically-linked carbohydrate chains of complex structures and functions. N-glycan chains are assembled in the endoplasmic reticulum and the Golgi by a controlled sequence of glycosyltransferase and glycosidase processing reactions involving dolichol intermediates. The assembly of O-glycans occurs in the Golgi and does not involve dolichol. For most reactions, families of glycosyltransferases exist; the expression of the individual enzymes within a family is often subject to complex regulation. The biosynthesis of N- and O-glycan is controlled at the level of gene expression, mRNA, enzyme protein activity and localization, and through substrate and cofactor concentrations at the site of synthesis. This complex regulation results in many hundreds of structures, the range of which varies in different species, cell types, tissue types, states of development and differentiation. In diseased cells, the relative proportions of these structures are often characteristically different from normal, and may be useful for the assessment of the stage of the disease and for diagnosis. Knowledge of disease-specific glycoprotein structures and their functions may be used therapeutically, in immunotherapy, in blocking cell adhesion or interfering with other binding or biological processes. Recently, some of the mechanisms underlying glycoprotein alterations in disease have been elucidated. This opens the possibility of an active interference in the disease process. The functions of glycans in diseased cells will become more clear with the tools of molecular biology and transgenic animal models.

negative: Sambucus nigra (black elder) as alternative treatment for cold and flu Common cold and flu are caused by common respiratory viral pathogens, which results in hospitalization and death in the world. Among the viral infections, influenza viruses have worldwide spread with major effects on health of societies. Change in antigenic structures of influenza viruses is associated with the lack of effective treatments. Therefore, the use of herbal medicine as alternative choice can be used for management of flu and cold. The flowers of Sambucus nigra or black elders have been approved by commission E for cold, and flu. Although, elders are used in different herbal formulates, but there is no comprehensive study. The subject of this review article was to summarize the efficacy of black elder in treatment of cold and flu. For preparing this manuscript, the electronic resources, books, and thesis were searched by key words of Sambucus, elder, cold, flu, and viral infections. The results of investigations exhibited that there are four clinical trials for elder berries, which it reduced the cold duration and severity (fever, pain, congestion, cough), while there is no clinical trial for elder flower on common cold and flu in spite of its approval by commission E. So, evaluating the efficacy of elder flowers in comparison with its berries and standard treatment on patients with viral respiratory infections should be the subject of large clinical studies.

negative: H1N1 Influenza Pandemic in Italy Revisited: Has the Willingness to Get Vaccinated Suffered in the Long Run? BACKGROUND: The aim of the study is to assess the long-term secondary effects of personal experience with the H1N1 pandemic of 2009/2010 and the perception of the institutional reaction to it on Italians’ willingness to get vaccinated in case of a novel influenza pandemic. DESIGN AND METHODS: We conducted 140 face-to-face interviews in the Registry Office of the Municipality of Milan, Italy, from October to December 2012. RESULTS: Willingness to get vaccinated during a novel influenza pandemic was best predicted by having been vaccinated against the seasonal flu in the past (OR=5.18; 95%CI: 1.40 to 19.13) and fear of losing one’s life in case of an infection with H1N1 (OR=4.09; 95%CI: 1.68 to 9.97). It was unaffected by the assessment of institutional performance. CONCLUSIONS: The findings of this study do not point to long-term secondary effects of the institutional handling of the H1N1 pandemic. The results highlight the fact that behavioural intention is not the same as behaviour, and that the former cannot simply be taken as an indicator of the latter.

negative: Excess mortality from seasonal influenza is negligible below the age of 50 in Israel: implications for vaccine policy PURPOSE: Evaluation of the severity of pandemic influenza requires reliable estimates of mortality attributable to the seasonal influenza. METHODS: Excess age-specific mortality during periods of influenza activity was evaluated in Israel during the period 1999–2006 for three death categories. For each respiratory year, the lowest monthly moving average for the mortality rate was subtracted from each month in the period of influenza activity. Average mortality rates in years with minimal influenza activity were deducted from corresponding months to exclude winter mortality unrelated to influenza. The sums of these results were used as estimates of excess mortality rates. RESULTS: Overall excess mortality rates ranged from 7.7 to 36.1 per 100,000 for all causes, and from 4.4 to 24.4 per 100,000 for respiratory and circulatory causes. Influenza was associated with an average of 869 (range 280–1,516) deaths annually from respiratory and circulatory diseases during seasons with significant influenza activity. About 90% of the influenza-associated mortality from respiratory and circulatory diseases was in the age group 65+ years and about 1% in the age group <50 years. The age group <50 years accounted for an annual average of seven deaths from respiratory and circulatory diseases. CONCLUSION: Annual mortality associated with seasonal influenza is highly variable. Under the age of 50 years, there is minimal seasonal influenza associated mortality. This information provides an important baseline for evaluating the severity of the A(H1N1) 2009 influenza pandemic, where persons under 50 years of age were often disproportionately represented.

negative: A Longitudinal Study on the Mental Health of General Population during the COVID-19 Epidemic in China Abstract In addition to being a public physical health emergency, Coronavirus disease 2019 (COVID-19) affected global mental health, as evidenced by panic-buying worldwide as cases soared. Little is known about changes in levels of psychological impact, stress, anxiety and depression during this pandemic. This longitudinal study surveyed the general population twice - during the initial outbreak, and the epidemic's peak four weeks later, surveying demographics, symptoms, knowledge, concerns, and precautionary measures against COVID-19. There were 1738 respondents from 190 Chinese cities (1210 first-survey respondents, 861 second-survey respondents; 333 respondents participated in both). Psychological impact and mental health status were assessed by the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. This study found that there was a statistically significant longitudinal reduction in mean IES-R scores (from 32.98 to 30.76, p<0.01) after 4 weeks. Nevertheless, the mean IES-R score of the first- and second-survey respondents were above the cut-off scores (>24) for PTSD symptoms, suggesting that the reduction in scores was not clinically significant. During the initial evaluation, moderate-to-severe stress, anxiety and depression were noted in 8.1%, 28.8% and 16.5%, respectively and there were no significant longitudinal changes in stress, anxiety and depression levels (p>0.05). Protective factors included high level of confidence in doctors, perceived survival likelihood and low risk of contracting COVID-19, satisfaction with health information, personal precautionary measures. As countries around the world brace for an escalation in cases, Governments should focus on effective methods of disseminating unbiased COVID-19 knowledge, teaching correct containment methods, ensuring availability of essential services/commodities, and providing sufficient financial support.

negative: Performance Evaluation of the Maxwell 16 System for Extraction of Influenza Virus RNA from Diverse Samples This study evaluated the performance of the Maxwell 16 System (Promega) for extraction of influenza virus (flu-v) RNA from diverse samples compared to a classical manual method (QIAamp Kit, QIAGEN). Following extraction by the two methods, all samples were analyzed by Real-time RT-PCR. Results revealed that the use of the standard Maxwell 16 protocol (Maxwell 16-S) resulted in good linearity and precision across a wide concentration range and higher sensitivity of detection from flu-v stock suspensions than the manual method. Compared with the latter method, Maxwell 16-S extracted RNA more efficiently (higher RNA yield and/or fewer PCR inhibitors) from throat swabs and bronchoalveolar lavage fluids, while both methods performed comparably on fecal samples from human and poultry in terms of overall threshold cycle values and detection rates although the Maxwell 16-S co-purified more inhibitors from fecal samples. The capacity of this system to remove inhibitors from fecal matrix was improved by using a modified Maxwell 16 protocol with a reduced sample input, which eliminated all false-negatives produced by the Maxwell 16-S. These findings suggest that the Maxwell 16 System is suitable for RNA extraction from multiple-source samples for diagnosis of influenza and viral load determination and that a proper reduction in starting sample volume may improve the detection of flu-v from complex matrices such as feces. Additionally, this system allows flexible sample throughput and labor-saving sample processing with little or no risk of cross-contamination.

negative: Single- and multiple viral respiratory infections in children: disease and management cannot be related to a specific pathogen BACKGROUND: The number of viral pathogens associated with pediatric acute respiratory tract infection (ARI) has grown since the introduction of reverse transcription real-time polymerase chain reaction (RT-PCR) assays. Multiple viruses are detected during a single ARI episode in approximately a quarter of all cases. The clinical relevance of these multiple detections is unclear, as is the role of the individual virus. We therefore investigated the correlation between clinical data and RT-PCR results in children with single- and multiple viral ARI. METHODS: Data from children with ARI were prospectively collected during two winter seasons. RT-PCR testing for 15 viruses was performed in 560 ARI episodes. In the patients with a single-viral etiology, clinical data, laboratory findings, patient management- and outcome data were compared between the different viruses. With this information, we compared data from children of whom RT-PCR data were negative, with children with single- and multiple viral positive results. RESULTS: The viral detection rate was 457/560 (81.6%) of which 331/560 (59.1%) were single infections and 126/560 (22.5%) were multiple infections. In single viral infections, some statistically significant differences in demographics, clinical findings, disease severity and outcome were found between children with different viral etiologies. However, no clinically recognizable pattern was established to be virus-specific. In a multivariate analysis, the only variables that were correlated with longer hospital stay were the use of oxygen and nebulizer therapy, irrespective of the viral pathogen. Children with RT-PCR positive test results had a significant higher disease severity, fever, length of hospital stay, days of extra oxygen supply, and days of antibiotic treatment than children with a negative RT-PCR test result. For children with single- versus children with multiple positive RT-PCR test results, these differences were not significant. CONCLUSIONS: Disease (severity), management and outcome in pediatric ARI are not associated with a specific virus. Single- and multiple viral ARI do not significantly differ with regard to clinical outcome and patient management. For general pediatrics, RT-PCR assays should be restricted to pathogens for which therapy is available or otherwise may have clinical consequences. Further research with an extended panel of RT-PCR assays and a larger number of inclusions is necessary to further validate our findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2118-6) contains supplementary material, which is available to authorized users.

negative: The effectiveness of non-pharmaceutical interventions in containing epidemics: a rapid review of the literature and quantitative assessment The number of confirmed COVID-19 cases has rapidly increased since discovery of the disease in December 2019. In the absence of medical countermeasures to stop the spread of the disease (i.e. vaccines), countries have responded by implementing a suite of non-pharmaceutical interventions (NPIS) to contain and mitigate COVID-19. Individual NPIs range in intensity (e.g. from lockdown to public health campaigns on personal hygiene), as does their impact on reducing disease transmission. This study uses a rapid review approach and investigates evidence from previous epidemic outbreaks to provide a quantitative assessment of the effectiveness of key NPIs used by countries to combat the COVID-19 pandemic. Results from the study are designed to help countries enhance their policy response as well as inform transition strategies by identifying which policies should be relaxed and which should not.

negative: Bat-derived influenza-like viruses H17N10 and H18N11 Shorebirds and waterfowls are believed to be the reservoir hosts for influenza viruses, whereas swine putatively act as mixing vessels. The recent identification of two influenza-like virus genomes (designated H17N10 and H18N11) from bats has challenged this notion. A crucial question concerns the role bats might play in influenza virus ecology. Structural and functional studies of the two major surface envelope proteins, hemagglutinin (HA) and neuraminidase (NA), demonstrate that neither has canonical HA or NA functions found in influenza viruses. However, putative functional modules and domains in other encoded proteins are conserved, and the N-terminal domain of the H17N10 polymerase subunit PA has a classical structure and function. Therefore, potential genomic reassortments of such influenza-like viruses with canonical influenza viruses cannot be excluded at this point and should be assessed.

negative: Coronaviruses Coronaviruses of humans were first identified more than 60 years ago from individuals with respiratory infections, mainly mild. Two different viruses, 229E and OC43 were initially recognized. Because of difficulty in isolating them using standard techniques, many of the early studies of their occurrence were seroepidemiologic. They were confirmed to be worldwide in distribution, and, in the North Temperate Zone, mainly occurring in the winter season. With the development of the reverse transcriptase polymerase chain reaction (PCR) technique, two additional distinct viruses have been identified, HKU1 and NL63. The four viruses have now been recognized as important in the etiology of common respiratory infections, second only to the rhinoviruses. In 2002, a previously unrecognized betacoronavirus emerged from a zoonotic reservoir in Southern China and spread during the following year to several major cities of the world. The resulting illness was termed Severe Acute Respiratory Syndrome (SARS) because of its potential lethality. More than 8,000 probable cases were reported during 2003, mainly from Hong Kong and mainland China, producing social and economic disruption in those areas affected. A constant feature of the outbreak was the importance of nosocomial spread. In spite of an estimated basic reproductive number higher than influenza, the outbreak was ended, in large part because of control of in-hospital transmission. In 2012, another betacoronavirus has emerged in the Arabian peninsula which is producing a somewhat similar illness, termed Middle East Respiratory Syndrome (MERS), also marked by extensive nosocomial transmission. The outcome of this emergence is currently unknown.

negative: Pulmonary embolism in COVID-19. When nothing is what it seems

negative: Host immune responses to influenza infection and vaccines: Lessons learned for all viral pandemic challenges

negative: Viral detection using a multiplex polymerase chain reaction–based assay in outpatients with upper respiratory infection Abstract We evaluated a commercial multiplex polymerase chain reaction (PCR) assay in a cross-sectional study among 81 adult and pediatric outpatients—40 cases with upper respiratory infection symptoms and 41 asymptomatic controls—from February to April 2008. Two specimens (throat swab and nasal swab) from each participant were tested using the EraGen MultiCode-PLx Respiratory Virus Panel that detects 17 viral targets. Throat swabs were also tested for Group A Streptococcus (GAS) by PCR. Respiratory viruses were detected in 22/40 (55%) cases and in 3/41 (7%) controls (P < 0.001). GAS was detected in 10 (25%) cases; GAS and respiratory virus co-infection was found in 4 (10%). Agreement between nasal and throat swabs for viral detection was 69% in cases and 95% in controls. Of 22 cases with a detectable virus, 12 (54%) were picked up by only 1 (throat or nasal) specimen, and the detection rate was increased by combining results of nasal and throat swab testing.

negative: Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19 BACKGROUND: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS: In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses.

negative: The outbreak of COVID-19 coronavirus and its impact on global mental health BACKGROUND: The current outbreak of COVID-19 coronavirus infection among humans in Wuhan (China) and its spreading around the globe is heavily impacting on the global health and mental health. Despite all resources employed to counteract the spreading of the virus, additional global strategies are needed to handle the related mental health issues. METHODS: Published articles concerning mental health related to the COVID-19 outbreak and other previous global infections have been considered and reviewed. COMMENTS: This outbreak is leading to additional health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear globally. Collective concerns influence daily behaviors, economy, prevention strategies and decision-making from policy makers, health organizations and medical centers, which can weaken strategies of COVID-19 control and lead to more morbidity and mental health needs at global level.

negative: Coronavirus disease 2019: a bibliometric analysis and review. OBJECTIVE On December 8, 2019, many cases of pneumonia with unknown etiology were first reported in Wuhan, China, subsequently identified as a novel coronavirus infection aroused worldwide concern. As the outbreak is ongoing, more and more researchers focused interest on the COVID-19. Therefore, we retrospectively analyzed the publications about COVID-19 to summarize the research hotspots and make a review, to provide reference for researchers in the world. MATERIALS AND METHODS We conducted a search in PubMed using the keywords "COVID-19" from inception to March 1, 2020. Identified and analyzed the data included title, corresponding author, language, publication time, publication type, research focus. RESULTS 183 publications published from 2020 January 14 to 2020 February 29 were included in the study. The first corresponding authors of the publications were from 20 different countries. Among them, 78 (42.6%) from the hospital, 64 (35%) from the university and 39 (21.3%) from the research institution. All the publications were published in 80 different journals. Journal of Medical Virology published most of them (n=25). 60 (32.8%) were original research, 29 (15.8%) were review, 20 (10.9%) were short communications. 68 (37.2%) epidemiology, 49 (26.8%) virology and 26 (14.2%) clinical features. CONCLUSIONS According to our review, China has provided a large number of research data for various research fields, during the outbreak of COVID-19. Most of the findings play an important role in preventing and controlling the epidemic around the world. With research on the COVID-19 still booming, new vaccine and effective medicine for COVID-19 will be expected to come out in the near future with the joint efforts of researchers worldwide.

negative: Antibody Responses to Influenza A/H1N1pdm09 Virus After Pandemic and Seasonal Influenza Vaccination in Healthcare Workers: A 5-Year Follow-up Study BACKGROUND: The 2009 influenza pandemic was caused by the A/H1N1pdm09 virus, which was subsequently included in the seasonal vaccine, up to 2016/2017, as the A/H1N1 strain. This provided a unique opportunity to investigate the antibody response to H1N1pdm09 over time. METHODS: Healthcare workers (HCWs) were immunized with the AS03-adjuvanted H1N1pdm09 vaccine in 2009 (N = 250), and subsequently vaccinated with seasonal vaccines containing H1N1pdm09 for 4 seasons (repeated group), <4 seasons (occasional group), or no seasons (single group). Blood samples were collected pre and at 21 days and 3, 6, and 12 months after each vaccination, or annually (pre-season) from 2010 in the single group. The H1N1pdm09-specific antibodies were measured by the hemagglutination inhibition (HI) assay. RESULTS: Pandemic vaccination robustly induced HI antibodies that persisted above the 50% protective threshold (HI titers ≥ 40) over 12 months post-vaccination. Previous seasonal vaccination and the duration of adverse events after the pandemic vaccination influenced the decision to vaccinate in subsequent seasons. During 2010/2011–2013/2014, antibodies were boosted after each seasonal vaccination, although no significant difference was observed between the repeated and occasional groups. In the single group without seasonal vaccination, 32% of HCWs seroconverted (≥4-fold increase in HI titers) during the 4 subsequent years, most of whom had HI titers <40 prior to seroconversion. When excluding these seroconverted HCWs, HI titers gradually declined from 12 to 60 months post–pandemic vaccination. CONCLUSIONS: Pandemic vaccination elicited durable antibodies, supporting the incorporation of adjuvant. Our findings support the current recommendation of annual influenza vaccination in HCWs. CLINICAL TRIALS REGISTRATION: NCT01003288.

negative: A model to forecast regional demand for COVID-19 related hospital beds COVID-19 threatens to overwhelm hospital facilities throughout the United States. We created an interactive, quantitative model that forecasts demand for COVID-19 related hospitalization based on county-level population characteristics, data from the literature on COVID-19, and data from online repositories. Using this information as well as user inputs, the model estimates a time series of demand for intensive care beds and acute care beds as well as the availability of those beds. The online model is designed to be intuitive and interactive so that local leaders with limited technical or epidemiological expertise may make decisions based on a variety of scenarios. This complements high-level models designed for public consumption and technically sophisticated models designed for use by epidemiologists. The model is actively being used by several academic medical centers and policy makers, and we believe that broader access will continue to aid community and hospital leaders in their response to COVID-19. Link to online model: https://surf.stanford.edu/covid-19-tools/covid-19/

negative: Challenges and cares to promote rational use of chloroquine and hydroxychloroquine in the management of coronavirus disease 2019 (COVID-19) pandemic: a timely review As a result of the 2019 coronavirus disease pandemic (COVID-19), there has been an urgent worldwide demand for treatments. Due to factors such as history of prescription for other infectious diseases, availability, and relatively low cost, the use of chloroquine (CQ) and hydroxychloroquine (HCQ) has been tested in vivo and in vitro for the ability to inhibit the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, even though investigators noted the therapeutic potential of these drugs, it is important to consider the toxicological risks and necessary care for rational use of CQ and HCQ. This study provides information on the main toxicological and epidemiological aspects to be considered for prophylaxis or treatment of COVID-19 using CQ but mainly HCQ, which is a less toxic derivative than CQ, and was shown to produce better results in inhibiting proliferation of SARS-CoV-2 based upon preliminary tests.

negative: Coronavirus: Short‐term pain but strong rebound likely ▪ Attention has understandably focused on limiting the damage from the short‐term effects of the coronavirus outbreak. But it's likely that, once disruption and uncertainty fade, the rebound in activity will be strong. It's important for firms to position themselves for such a recovery. ▪ Historical evidence supports this view. In the past 200 years, short recessions have typically been followed by robust recovery. Long‐term impacts from natural disasters have generally only been evident for specific hazards. Except for AIDS, longer‐term pandemic effects also appear to have been contained. ▪ Surveys during the 2003 SARS and 2009 influenza outbreaks highlight one explanation for time‐limited impacts. Public fears increased alongside rising infection rates, but they dissipated promptly as outbreaks came under control. ▪ Our modelling is consistent with these stylised facts. In our coronavirus pandemic scenario, global growth grinds to a halt in Q2 2020 but then rebounds to a rapid pace within a year. With much of the initial output loss recovered in a relatively short period of time, long‐term impacts are limited. ▪ But there are risks to this view. The period of disruption could be longer than anticipated, depending on the potential spread and seasonality of COVID‐19 and policy actions to mitigate the fallout. Opinion polls also highlight the potential risk of larger, more persistent effects for some countries. ▪ Moreover, coronavirus‐related weakness and associated financial distress could expose other key vulnerabilities ‐ for example related to deteriorating corporate sector balance sheets and fragile trade relations. These would be expected to have persistent effects on global activity over the coming years.

negative: Respiratory viral pathogens among Singapore military servicemen 2009 – 2012: epidemiology and clinical characteristics BACKGROUND: Few studies have comprehensively described tropical respiratory disease surveillance in military populations. There is also a lack of studies comparing clinical characteristics of the non-influenza pathogens with influenza and amongst themselves. METHODS: From May 2009 through October 2012, 7733 consenting cases of febrile respiratory illness (FRI) (temperature [greater than or equal to]37.5degreesC with cough or sorethroat) and controls in the Singapore military had clinical data and nasal washes collected prospectively. Nasal washes underwent multiplex PCR, and the analysis was limited to viral mono-infections. RESULTS: 49% of cases tested positive for at least one virus, of whom 10% had multiple infections. 53% of the FRI cases fulfilled the definition of influenza-like illness (ILI), of whom 52% were positive for at least one virus. The most frequent etiologies for mono-infections among FRI cases were Influenza A(H1N1)pdm09 (13%), Influenza B (13%) and coxsackevirus (9%). The sensitivity, specificity, positive predictive value and negative predictive value of ILI for influenza among FRI cases were 72%, 48%, 40% and 69% respectively. On logistic regression, there were marked differences in the prevalence of different symptoms and signs between viruses with fever more prevalent amongst influenza and adenovirus infections than other viruses. CONCLUSION: There are multiple viral etiologies for FRI and ILI with differing clinical symptoms in the Singapore military. Influenza and coxsackevirus were the most common etiology for FRI, while influenza and adenoviruses displayed the most febrile symptoms. Further studies should explore these differences and possible interventions.

negative: The swine flu and its impacts on tourism in Brunei Abstract This paper demonstrates how to disentangle the impacts of the swine flu on tourism in Brunei, which overlaps with the continued effects of the 2008 global financial crisis that occurred earlier using the auto regressive integrated moving average and intervention time series analysis methods. Estimating the impacts of the swine flu for the first 12 months' post-swine flu period, we have predicted the number of tourists by fitting two auto regressive integrated moving average models: one for the swine flu and another for the global financial crisis which occurred and affected the number of tourist arrivals; and one intervention time series analysis model. It is shown that the number of tourists have been reduced significantly due to both the swine flu and the global financial crisis, which is reconfirmed by testing the coefficients of the fitted intervention time series analysis model. It is found that a small country like Brunei lost nearly 30, 000 (15%) tourists and B$15 million dollars due to the swine flu during the first twelve months’ post-swine flu period.

negative: Immunogenicity difference between the SARS coronavirus and the bat SARS-like coronavirus spike (S) proteins Abstract SARS-like coronavirus (SL-CoV) in bats have a similar genomic organization to the human SARS-CoV. Their cognate gene products are highly conserved with the exception of the N-terminal region of the S proteins, which have only 63–64% sequence identity. The N-terminal region of coronavirus S protein is responsible for virus–receptor interaction. In this study, the immunogenicity of the SL-CoV S protein (SSL) was studied and compared with that of SARS-CoV (SSARS). DNA immunization in mice with SSL elicited a high titer of antibodies against HIV-pseudotyped SSL. The sera had low cross-reactivity, but no neutralization activity, for the HIV-pseudotyped SSARS. Studies using wild bat sera revealed that it is highly likely that the immunodominant epitopes overlap with the major neutralizing sites of the SL-CoV S protein. These results demonstrated that SL-CoV and SARS-CoV shared only a limited number of immunogenic epitopes in their S proteins and the major neutralization epitopes are substantially different. This work provides useful information for future development of differential serologic diagnosis and vaccines for coronaviruses with different S protein sequences.

negative: Compare the differences of synonymous codon usage between the two species within cardiovirus BACKGROUND: Cardioviruses are positive-strand RNA viruses in the Picornaviridae family that can cause enteric infection in rodents and also been detected at lower frequencies in other mammals such as pigs and human beings. The Cardiovirus genus consists two distinct species: Encephalomyocarditis virus (EMCV) and Theilovirus (ThV). There are a lot differences between the two species. In this study, the differences of codon usage in EMCV and ThV were compared. RESULTS: The mean ENC values of EMCV and ThV are 54.86 and 51.08 respectively, higher than 40.And there are correlations between (C+G)(12)% and (C+G)(3)% for both EMCV and ThV (r = -0.736;r = 0.986, P < 0.01, repectively). For ThV the (C+G)(12)%, (C+G)(3)%, axis f'(1 )and axis f'(2 )had a significant correlations respectively but not for EMCV. According to the RSCU values, the EMCV species seemed to prefer U, G and C ending codon, while the ThV spice seemed to like using U and A ending codon. However, in both genus AGA for Arg, AUU for Ile, UCU for Ser, and GGA for Gly were chosen preferentially. Correspondence analysis detected one major trend in the first axis (f'(1)) which accounted for 22.89% of the total variation, and another major trend in the second axis (f'(2)) which accounted for 17.64% of the total variation. And the plots of the same serotype seemed at the same region at the coordinate. CONCLUSION: The overall extents of codon usage bias in both EMCV and ThV are low. The mutational pressure is the main factor that determines the codon usage bias, but the (C+G) content plays a more important role in codon usage bias for ThV than for EMCV. The synonymous codon usage pattern in both EMCV and ThV genes is gene function and geography specific, but not host specific. Maybe the serotype is one factor effected the codon bias for ThV, and location has no significant effect on the variations of synonymous codon usage in these virus genes.

negative: Has there been an increased interest in smoking cessation during the first months of the COVID-19 pandemic? A Google Trends study [Figure: see text]

negative: Fogarty International Center collaborative networks in infectious disease modeling: Lessons learnt in research and capacity building Abstract Due to a combination of ecological, political, and demographic factors, the emergence of novel pathogens has been increasingly observed in animals and humans in recent decades. Enhancing global capacity to study and interpret infectious disease surveillance data, and to develop data-driven computational models to guide policy, represents one of the most cost-effective, and yet overlooked, ways to prepare for the next pandemic. Epidemiological and behavioral data from recent pandemics and historic scourges have provided rich opportunities for validation of computational models, while new sequencing technologies and the ‘big data’ revolution present new tools for studying the epidemiology of outbreaks in real time. For the past two decades, the Division of International Epidemiology and Population Studies (DIEPS) of the NIH Fogarty International Center has spearheaded two synergistic programs to better understand and devise control strategies for global infectious disease threats. The Multinational Influenza Seasonal Mortality Study (MISMS) has strengthened global capacity to study the epidemiology and evolutionary dynamics of influenza viruses in 80 countries by organizing international research activities and training workshops. The Research and Policy in Infectious Disease Dynamics (RAPIDD) program and its precursor activities has established a network of global experts in infectious disease modeling operating at the research-policy interface, with collaborators in 78 countries. These activities have provided evidence-based recommendations for disease control, including during large-scale outbreaks of pandemic influenza, Ebola and Zika virus. Together, these programs have coordinated international collaborative networks to advance the study of emerging disease threats and the field of computational epidemic modeling. A global community of researchers and policy-makers have used the tools and trainings developed by these programs to interpret infectious disease patterns in their countries, understand modeling concepts, and inform control policies. Here we reflect on the scientific achievements and lessons learnt from these programs (h-index = 106 for RAPIDD and 79 for MISMS), including the identification of outstanding researchers and fellows; funding flexibility for timely research workshops and working groups (particularly relative to more traditional investigator-based grant programs); emphasis on group activities such as large-scale modeling reviews, model comparisons, forecasting challenges and special journal issues; strong quality control with a light touch on outputs; and prominence of training, data-sharing, and joint publications.

negative: Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade Here, we review the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, including acute kidney injury, and examine the potential effects of ARBs on the outcomes of patients with COVID-19. Lastly, we discuss the clinical management of COVID-19 patients with existing chronic renal disorders, particularly those in dialysis and with kidney transplants.

negative: Prioritizing and Analyzing the Role of Climate and Urban Parameters in the Confirmed Cases of COVID-19 Based on Artificial Intelligence Applications Nowadays, an infectious disease outbreak is considered one of the most destructive effects in the sustainable development process. The outbreak of new coronavirus (COVID-19) as an infectious disease showed that it has undesirable social, environmental, and economic impacts, and leads to serious challenges and threats. Additionally, investigating the prioritization parameters is of vital importance to reducing the negative impacts of this global crisis. Hence, the main aim of this study is to prioritize and analyze the role of certain environmental parameters. For this purpose, four cities in Italy were selected as a case study and some notable climate parameters—such as daily average temperature, relative humidity, wind speed—and an urban parameter, population density, were considered as input data set, with confirmed cases of COVID-19 being the output dataset. In this paper, two artificial intelligence techniques, including an artificial neural network (ANN) based on particle swarm optimization (PSO) algorithm and differential evolution (DE) algorithm, were used for prioritizing climate and urban parameters. The analysis is based on the feature selection process and then the obtained results from the proposed models compared to select the best one. Finally, the difference in cost function was about 0.0001 between the performances of the two models, hence, the two methods were not different in cost function, however, ANN-PSO was found to be better, because it reached to the desired precision level in lesser iterations than ANN-DE. In addition, the priority of two variables, urban parameter, and relative humidity, were the highest to predict the confirmed cases of COVID-19.

negative: Insight into 2019 novel coronavirus — an updated intrim review and lessons from SARS-CoV and MERS-CoV Abstract Background The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus entitled 2019 novel coronavirus (2019-nCoV), has become a global threat. Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions. Methods Based on recently published literatures, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV) infection. Results The genome of 2019-nCoV partially resembled SARS-CoV and MERS-CoV, and indicating a bat origin. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Clinical presentation and pathology of COVID-19 greatly resembled SARS and MERS, with less upper respiratory and gastrointestinal symptoms, and more exudative lesions in post-mortems. Potential treatments included remdesivir, chloroquine, tocilizumab, convalescent plasma and vaccine immunization (when possible). Conclusion The initial experience from the current pandemic and lessons from the previous two pandemics can help improve future preparedness plans and combat disease progression.

negative: Flu Vaccination Attitudes, Behaviours, and Knowledge among Health Workers The aim of this work is to evaluate the attitudes, behaviours, and knowledge of health workers employed at an Italian University Hospital on the topic of vaccinations and in regard to flu vaccination. To this end, the study provided for the articulation of a computerised questionnaire on the digital platform EUSurvey which was administered online via e-mail to a sample of 457 health workers, in the period between November 2018 and March 2019. The data were subjected to descriptive and inferential statistical analysis. In particular, a logistic regression analysis was carried out in order to evaluate the relationship between the variables collected and the dichotomous outcome (vaccinated/unvaccinated subjects in the 2018–2019 season). The results, in line with what has been reported by the literature, highlighted that vaccine hesitancy is prevalent also among health workers. Furthermore, according to our study, only 30.6% of the health care workers had the flu vaccination. The survey points out the need to plan educational and informative interventions aimed at changing the attitudes, behaviours, and knowledge of health workers in the field of flu vaccination, for the purpose of protecting the health of healthcare personnel and their patients.

negative: Perceptions Related to Bird-to-Human Avian Influenza, Influenza Vaccination, and Use of Face Mask BACKGROUND: H5N1 avian influenza may become pandemic in humans in the near future. According to the severe acute respiratory syndrome (SARS) experience, anticipation of the pandemic may have impact on behaviors related to influenza vaccination (IV) and relevant public health behaviors such as wearing a face mask when having influenza-like-illnesses (ILI), which would play an important role in the control of human avian influenza outbreaks. This paper investigated the prevalence and factors related to IV uptake and use of face mask in public venues when having ILI symptoms. METHODS: An anonymous cross-sectional population-based random telephone survey of 302 Hong Kong Chinese adults aged 18–60, using a structured questionnaire, was conducted in November 2005. RESULTS: In the last 3 months, 17.9% of the respondents received IV; 36.6% of those presenting ILI symptoms often used face mask in public venues. Anticipation of a bird-to-human H5N1 outbreak, perceptions that such an outbreak would be worse than SARS, that IV was efficacious in preventing bird-to-human avian influenza transmission were associated with the studied IV behavior (OR=2.64–3.97, p < 0.05). Exposure to live birds, perceived similar symptoms between influenza and bird-to-human H5N1 avian influenza, that bird-to-human avian influenza was more lethal than SARS were predictive use of face mask when having ILI symptoms (OR = 4.25–8.34, p < 0.05). CONCLUSION: The prevalence of IV and use of face mask in the study population may be increasing, which may be related to concerns of avian influenza. Perceptions related to human avian influenza were associated with IV and mask use behaviors. This can potentially be turned into opportunities of promoting desirable public health behaviors.

negative: Decline in PM2.5 Concentrations over Major Cities Around the World Associated with COVID-19 Abstract The COVID-19 started from Wuhan city in China, slowly spread across the globe after December 2019. Due to movement of people from one city to other cities, one country to other countries, infection spreads and COVID-19 became a pandemic. Efforts were made at local, regional and national levels to lockdown the movement of people and to keep infected one in quarantine or isolation to stop the spread of COVID-19. The traffic, market and small industries were closed, as a result pronounced decline in the concentrations of particulate matters (PM) were observed. Normally these sources contribute to the high concentrations of particulate matters (PM2.5) which represents air quality of a location. In this short communication, we present analysis of PM2.5 of major cities (New York, Los Angeles, Zaragoza, Rome, Dubai, Delhi, Mumbai, Beijing and Shanghai) around the world suffered severely with the COVID-19. Our analysis shows decline in PM2.5 concentration due to lockdown, mainly due to less movement of people to keep “social distancing” to control the spread of CORONA-19. The low concentrations of PM2.5 reflect the efforts made in the cities to curb the spread of infection, that improve air quality.

negative: Intimate Partner Violence Victimization and Perpetration among U.S. Adults during COVID-19: A Brief Report Importance: Anecdotal evidence such as increased calls to domestic violence (DV) hotlines across the globe suggest that there may be an increase of IPV prevalence in association with the COVID-19 outbreak; however, no study has investigated this phenomenon empirically. Objective: To evaluate the association between COVID-19 related conditions and recent use or experience of IPV (since the pandemic outbreak in the U.S). Design, Setting, and Participants: This cross-sectional study analyzed data collected online from a sample of noninstitutionalized adults (age 18+) in the U.S. (N=2,045). More than half of the sample self-identified as being in an intimate relationship at the time of the study. Main Outcomes and Measures: A four-item tool was used to assess IPV perpetration and victimization since the outbreak of COVID-19. The rapid tool inquired about two forms of IPV, psychological and physical. Participants self-reported demographic data and recent health histories, including COVID-19 tests results, related symptoms and degree of personal social distancing. We hypothesized that COVID-19 related factors would increase risks of IPV. Results: In this study, self-reported COVID-19 impacted respondents had an increased risk of IPV victimization and perpetration. Among those who reported having symptoms consistent with coronavirus, but were denied access to testing, psychological IPV victimization was 3 times greater than those who did not (Exp[B] =3.15, [1.19, 2.29] p <.05). For participants who reported testing positive to COVID-19, the odds of using psychological IPV (Exp[B] =3.24, [1.18, 8.89] p <.05) and physical IPV (Exp[B]=3.02, [1.12, 8.17] p <.05) against an intimate partner increased by more than 3 times. Conclusions and Relevance: Patient education and community outreach/health care system initiatives focused on IPV risk behaviors may help reduce the potential development of IPV. Continued surveillance is imperative to improve health and well-being along with effective intervention development and implementation.

negative: Inhibition of the PI3K/AKT Signaling Pathway or Overexpression of Beclin1 Blocks Reinfection of Streptococcus pneumoniae After Infection of Influenza A Virus in Severe Community-Acquired Pneumonia Streptococcus pneumoniae (S. pneumoniae) and viruses are considered as primary risks of community-acquired pneumonia (CAP), and the effects of co-infection bacterial and virus in the prognosis of patients with severe CAP (SCAP) are poorly described. Therefore, this study is conducted to investigate the regulation of Beclin1-PI3K/AKT axis in reinfection of S. pneumoniae after influenza A virus in mice model of bronchoalveolar lavage fluid (BALF). Samples of sputum and BALF were collected from patients with SCAP for etiological detection. The expression of each gene was determined by RT-qPCR and western blot analysis. Influenza A/PR/8/34 and S. pneumoniae were used to establish the mice model of reinfection pneumonia. The virus quantity, expression levels of inflammatory factors, bacterial load, and myeloperoxidase (MPO) activity were tested. HE staining was applied to observe histopathology of lung tissue. The expression of Beclin1 was downregulated and the PI3K/AKT pathway was activated in viral pneumonia. In vivo experiment, the reinfection of S. pneumoniae following influenza A virus infection increased the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice. In contrast, inhibition of the PI3K/AKT pathway or overexpression of Beclin1 reduced the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice reinfected with S. pneumoniae after influenza A virus infection. Collectively, our study demonstrates that inhibition of the PI3K/AKT signaling pathway or overexpressed Beclin1 alleviates reinfection of S. pneumoniae after influenza A virus infection in SCAP.

negative: Analyses of Merging Clinical and Viral Genetic Data for Influenza Surveillance. The annual influenza vaccine is one of the most common public health interventions and is universally recommended for all individuals older than six months. Vaccine composition depends on viruses circulating over the past flu season and are estimated to be the most prevalent and representative strains in the current season. Here, we use clinical data outfitted with viral genetics to characterize confirmed influenza cases from the past two flu seasons and genetically compare them to the strains that they were vaccinated against that year. We show that case similarities to vaccine strains differ by geographic region and that the vaccines appear to have different levels of effectiveness by region. This study demonstrates the value of merging viral genetics with clinical data. Further research is needed to formally evaluate whether this improves biosurveillance efforts and enhances efficacy of influenza vaccines.

negative: Characteristics of COVID-19 infection in Beijing Abstract Background Since the first case of a novel coronavirus (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Beijing. We analyzed the data of 262 confirmed cases to determine the clinical and epidemiological characteristics of COVID-19 in Beijing. Methods We collected patients who were transferred by Beijing Emergency Medical Service to the designated hospitals. The information on demographic, epidemiological, clinical, laboratory test for the COVID-19 virus, diagnostic classification, cluster case and outcome were obtained. Furthermore we compared the characteristics between severe and common confirmed cases which including mild cases, no-pneumonia cases and asymptomatic cases, and we also compared the features between COVID-19 and 2003 SARS. Findings By Feb 10, 2020, 262 patients were transferred from the hospitals across Beijing to the designated hospitals for special treatment of the COVID-19 infected by Beijing emergency medical service. Among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11(4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases respectively. The median age of patients was 47.5 years old and 48.5% were male. 192 (73.3%) patients were residents of Beijing, 50 (26.0%) of which had been to Wuhan, 116 (60.4%) had close contact with confirmed cases, 21 (10.9%) had no contact history. The most common symptoms at the onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%). The median incubation period was 6.7 days, the interval time from between illness onset and seeing a doctor was 4.5 days. As of Feb 10, 17.2% patients have discharged and 81.7% patients remain in hospital in our study, the fatality of COVID-19 infection in Beijing was 0.9%. Interpretation On the basis of this study, we provided the ratio of the COVID-19 infection on the severe cases to the mild, asymptomatic and non-pneumonia cases in Beijing. Population was generally susceptible, and with a relatively low fatality rate. The measures to prevent transmission was very successful at early stage, the next steps on the COVID-19 infection should be focused on early isolation of patients and quarantine for close contacts in families and communities in Beijing. Funding Beijing Municipal Science and Technology Commission and Ministry of Science and Technology.

negative: Mining Social Media and Web Searches For Disease Detection Web-based social media is increasingly being used across different settings in the health care industry. The increased frequency in the use of the Internet via computer or mobile devices provides an opportunity for social media to be the medium through which people can be provided with valuable health information quickly and directly. While traditional methods of detection relied predominately on hierarchical or bureaucratic lines of communication, these often failed to yield timely and accurate epidemiological intelligence. New web-based platforms promise increased opportunities for a more timely and accurate spreading of information and analysis. This article aims to provide an overview and discussion of the availability of timely and accurate information. It is especially useful for the rapid identification of an outbreak of an infectious disease that is necessary to promptly and effectively develop public health responses. These web-based platforms include search queries, data mining of web and social media, process and analysis of blogs containing epidemic key words, text mining, and geographical information system data analyses. These new sources of analysis and information are intended to complement traditional sources of epidemic intelligence. Despite the attractiveness of these new approaches, further study is needed to determine the accuracy of blogger statements, as increases in public participation may not necessarily mean the information provided is more accurate.

negative: Interplay between cost and effectiveness in influenza vaccine uptake: a vaccination game approach Pre-emptive vaccination is regarded as one of the most protective measures to control influenza outbreak. There are mainly two types of influenza viruses—influenza A and B with several subtypes—that are commonly found to circulate among humans. The traditional trivalent (TIV) flu vaccine targets two strains of influenza A and one strain of influenza B. The quadrivalent (QIV) vaccine targets one extra B virus strain that ensures better protection against influenza; however, the use of QIV vaccine can be costly, hence impose an extra financial burden to society. This scenario might create a dilemma in choosing vaccine types at the individual level. This article endeavours to explain such a dilemma through the framework of a vaccination game, where individuals can opt for one of the three options: choose either of QIV or TIV vaccine or none. Our approach presumes a mean-field framework of a vaccination game in an infinite and well-mixed population, entangling the disease spreading process of influenza with the coevolution of two types of vaccination decision-making processes taking place before an epidemic season. We conduct a series of numerical simulations as an attempt to illustrate different scenarios. The framework has been validated by the so-called multi-agent simulation (MAS) approach.

negative: Surveillance for emerging respiratory viruses Summary Several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 15 years. In 2003, WHO issued a worldwide alert for an unknown emerging illness, later named severe acute respiratory syndrome (SARS). The disease caused by a novel coronavirus (SARS-CoV) rapidly spread worldwide, causing more than 8000 cases and 800 deaths in more than 30 countries with a substantial economic impact. Since then, we have witnessed the emergence of several other viral respiratory pathogens including influenza viruses (avian influenza H5N1, H7N9, and H10N8; variant influenza A H3N2 virus), human adenovirus-14, and Middle East respiratory syndrome coronavirus (MERS-CoV). In response, various surveillance systems have been developed to monitor the emergence of respiratory-tract infections. These include systems based on identification of syndromes, web-based systems, systems that gather health data from health facilities (such as emergency departments and family doctors), and systems that rely on self-reporting by patients. More effective national, regional, and international surveillance systems are required to enable rapid identification of emerging respiratory epidemics, diseases with epidemic potential, their specific microbial cause, origin, mode of acquisition, and transmission dynamics.

negative: Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey BACKGROUND: China is at greatest risk of the Pandemic (H1N1) 2009 due to its huge population and high residential density. The unclear comprehension and negative attitudes towards the emerging infectious disease among general population may lead to unnecessary worry and even panic. The objective of this study was to investigate the Chinese public response to H1N1 pandemic and provide baseline data to develop public education campaigns in response to future outbreaks. METHODS: A close-ended questionnaire developed by the Chinese Center for Disease Control and Prevention was applied to assess the knowledge, attitudes and practices (KAP) of pandemic (H1N1) 2009 among 10,669 responders recruited from seven urban and two rural areas of China sampled by using the probability proportional to size (PPS) method. RESULTS: 30.0% respondents were not clear whether food spread H1N1 virusand. 65.7% reported that the pandemic had no impact on their life. The immunization rates of the seasonal flu and H1N1vaccine were 7.5% and 10.8%, respectively. Farmers and those with lower education level were less likely to know the main transmission route (cough or talk face to face). Female and those with college and above education had higher perception of risk and more compliance with preventive behaviors. Relationships between knowledge and risk perception (OR = 1.69; 95%CI 1.54-1.86), and knowledge and practices (OR = 1.57; 95%CI 1.42-1.73) were found among the study subjects. With regard to the behavior of taking up A/H1N1 vaccination, there are several related factors found in the current study population, including the perception of life disturbed (OR = 1.29; 95%CI 1.11-1.50), the safety of A/H1N1 vaccine (OR = 0.07; 95%CI 0.04-0.11), the knowledge of free vaccination policy (OR = 7.20; 95%CI 5.91-8.78), the state's priority vaccination strategy(OR = 1.33; 95%CI 1.08-1.64), and taking up seasonal influenza vaccine behavior (OR = 4.69; 95%CI 3.53-6.23). CONCLUSIONS: This A/H1N1 epidemic has not caused public panic yet, but the knowledge of A/H1N1 in residents is not optimistic. Public education campaign may take the side effects of vaccine and the knowledge about the state's vaccination strategy into account.

negative: Apical plasma membrane proteins are not obligatorily stored in secretory granules in exocrine cells. Exocrine cells are epithelial cells in which secretory granules undergo fusion with the apical plasma membrane upon secretagogue stimulation. Several apical plasma membrane proteins have been found in secretory granules in cells from pancreas and salivary glands raising the possibility that incorporation into secretory granules followed by exocytosis of the granules accounts for their insertion into the apical plasma membrane. To test this hypothesis, we have expressed the influenza hemagglutinin (HA) in pancreatic AR42J cells, which make zymogen-like granules upon incubation with dexamethasone. The influenza virus HA is known to be specifically targeted to the apical plasma membrane of epithelial cells that lack a regulated pathway and is also known to be excluded from secretory granules in virally-infected pituitary AtT20 cells. Localization of the protein by immunofluorescence microscopy revealed that it accumulated at the plasma membrane of the transfected AR42J cells. HA was not observed in the amylase-rich secretory granules. By immunolabeling of ultrathin cryosections of the transfected cells, HA was also found exclusively on the cell surface, with label over secretory granules not exceeding that seen in control, untransfected cells. In addition, in cell fractionation experiments performed on radiolabeled AR42J cell transformants, HA was not detectable in the secretory granule fractions. These results indicate that HA is not efficiently stored in mature secretory granules and is likely to reach the cell surface via constitutive transport pathways.

negative: Avian Influenza: a global threat needing a global solution There have been three influenza pandemics since the 1900s, of which the 1919–1919 flu pandemic had the highest mortality rates. The influenza virus infects both humans and birds, and mutates using two mechanisms: antigenic drift and antigenic shift. Currently, the H5N1 avian flu virus is limited to outbreaks among poultry and persons in direct contact to infected poultry, but the mortality rate among infected humans is high. Avian influenza (AI) is endemic in Asia as a result of unregulated poultry rearing in rural areas. Such birds often live in close proximity to humans and this increases the chance of genetic re-assortment between avian and human influenza viruses which may produce a mutant strain that is easily transmitted between humans. Once this happens, a global pandemic is likely. Unlike SARS, a person with influenza infection is contagious before the onset of case-defining symptoms which limits the effectiveness of case isolation as a control strategy. Researchers have shown that carefully orchestrated of public health measures could potentially limit the spread of an AI pandemic if implemented soon after the first cases appear. To successfully contain and control an AI pandemic, both national and global strategies are needed. National strategies include source surveillance and control, adequate stockpiles of anti-viral agents, timely production of flu vaccines and healthcare system readiness. Global strategies such as early integrated response, curbing the disease outbreak at source, utilization of global resources, continuing research and open communication are also critical.

negative: The Acute Respiratory Infection Consortium: A Multi-Site, Multi-Disciplinary Clinical Research Network in the Department of Defense INTRODUCTION: Acute respiratory infections (ARI) result in substantial annual morbidity among military personnel and decrease operational readiness. Herein, we summarize the research efforts of the Infectious Disease Clinical Research Program (IDCRP) related to ARIs. METHODS: The ARI Research Area of the IDCRP was established in response to the 2009 emergence of pandemic influenza A/H1N1. That year, IDCRP investigators deployed the ARI Consortium Natural History Study (ARIC NHS), a multi-centered, longitudinal observational study to assess etiology, epidemiology, and clinical characteristics of influenza-like illness (ILI) and severe acute respiratory infections (SARI) in the U.S. military. The success of this initial effort spurred implementation of several new initiatives. These include the FluPlasma trial, designed to evaluate the efficacy of hyperimmune anti-influenza plasma for the treatment of severe influenza; the self-administered live-attenuated influenza vaccine (SNIF) trial, which assessed the immunogenicity and acceptance of a self-administered live-attenuated influenza vaccine in military personnel; the Study to Address Threats of ARI in Congregate Military Populations (ATARI), a prospective study of ILI transmission, etiology and epidemiology in recruits; and the Flu Breath Test (FBT) study, a preliminary study of exhaled volatile organic compounds (VOC) in influenza patients. In addition, the InFLUenza Patient-Reported Outcome (FLU-PRO) survey, a daily diary to measure influenza symptoms during clinical trials, was developed. Lastly, the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study, a two-year randomized trial designed to compare the effectiveness of the three types of licensed vaccines, launched in Fall 2018. RESULTS: The on-going ARIC NHS has enrolled over 2000 ILI and SARI cases since its inception, providing data on burden and clinical manifestations of ARI in military personnel and their families. The FluPlasma 2 trial concluded subject enrollment in 2018. Preliminary results from ATARI study show a high frequency of respiratory viruses circulating during the first two weeks of recruit training. Based on assessment of FLU-PRO responses, which were found to be reliable and reproducible, the survey may be a useful tool in clinical trials and epidemiological studies. The Flu Breath Study will complete enrollment in 2019. Findings from PAIVED are intended to provide evidence needed for assessing influenza vaccination policy in the military. CONCLUSIONS: The ARI burden in the armed services remains significant every year and the threat is dynamic given emergent and evolving threats, such as influenzas. With strong successes to date, future initiatives of the ARI Research Area will focus on interventional studies, ARI transmission dynamics in congregate military settings, and determinants of risk of pandemic influenza and other emergent respiratory viruses.

negative: Optimal strategies for quarantine stopping in France. General expected patterns of strategies focusing on contact between age groups Due to the COVID-19 pandemic, many countries have implemented a complete lock-down of their population that may not be sustainable for long. To identify the best strategy to replace this full lock-down, sophisticated models that rely on mobility data have been developed. In this study, using the example of France as a case-study, we develop a simple model considering contacts between age classes to derive the general impact of partial lock-down strategies targeted at specific age groups. We found that epidemic suppression can only be achieved by targeting isolation of young and middle age groups with high efficiency. All other strategies tested result in a flatter epidemic curve, with outcomes in (e.g. mortality and health system over-capacity) dependent of the age groups targeted and the isolation efficiency. Targeting only the elderly can decrease the expected mortality burden, but in proportions lower than more integrative strategies involving several age groups. While not aiming to provide quantitative forecasts, our study shows the benefits and constraints of different partial lock-down strategies, which could help guide decision-making.

negative: Reassuring and managing patients with concerns about swine flu: Qualitative interviews with callers to NHS Direct BACKGROUND: During the early stages of the 2009 swine flu (influenza H1N1) outbreak, the large majority of patients who contacted the health services about the illness did not have it. In the UK, the NHS Direct telephone service was used by many of these patients. We used qualitative interviews to identify the main reasons why people approached NHS Direct with concerns about swine flu and to identify aspects of their contact which were reassuring, using a framework approach. METHODS: 33 patients participated in semi-structured interviews. All patients had telephoned NHS Direct between 11 and 14 May with concerns about swine flu and had been assessed as being unlikely to have the illness. RESULTS: Reasons for seeking advice about swine flu included: the presence of unexpectedly severe flu-like symptoms; uncertainties about how one can catch swine flu; concern about giving it to others; pressure from friends or employers; and seeking 'peace of mind.' Most participants found speaking to NHS Direct reassuring or useful. Helpful aspects included: having swine flu ruled out; receiving an alternative explanation for symptoms; clarification on how swine flu is transmitted; and the perceived credibility of NHS Direct. No-one reported anything that had increased their anxiety and only one participant subsequently sought additional advice about swine flu from elsewhere. CONCLUSIONS: Future major incidents involving other forms of chemical, biological or radiological hazards may also cause large numbers of unexposed people to seek health advice. Our data suggest that providing telephone triage and information is helpful in such instances, particularly where advice can be given via a trusted, pre-existing service.

negative: Dating the time of viral subtype divergence Precise dating of viral subtype divergence enables researchers to correlate divergence with geographic and demographic occurrences. When historical data are absent (that is, the overwhelming majority), viral sequence sampling on a time scale commensurate with the rate of substitution permits the inference of the times of subtype divergence. Currently, researchers use two strategies to approach this task, both requiring strong conditions on the molecular clock assumption of substitution rate. As the underlying structure of the substitution rate process at the time of subtype divergence is not understood and likely highly variable, we present a simple method that estimates rates of substitution, and from there, times of divergence, without use of an assumed molecular clock. We accomplish this by blending estimates of the substitution rate for triplets of dated sequences where each sequence draws from a distinct viral subtype, providing a zeroth-order approximation for the rate between subtypes. As an example, we calculate the time of divergence for three genes among influenza subtypes A-H3N2 and B using subtype C as an outgroup. We show a time of divergence approximately 100 years ago, substantially more recent than previous estimates which range from 250 to 3800 years ago.

negative: Potential Immunotherapeutic Targets For Hypoxia Due to COVI-FLU The world is currently embroiled in a pandemic of coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel betacoronavirus SARS-CoV-2. The severity of COVID-19 disease ranges from asymptomatic to fatal acute respiratory distress syndrome (ARDS). In few patients, the disease undergoes phenotypic differentiation between 7-14 days of acute illness, either resulting in full recovery or symptom escalation. However, the mechanism of such variation is not clear, but the facts suggest that patient's immune status, co-morbidities, and the systemic effects of the viral infection (potentially depending on the SARS-CoV-2 strain involved) play a key role. Subsequently, patients with the most severe symptoms tend to have poor outcomes, manifest severe hypoxia, and possess elevated levels of pro-inflammatory cytokines (including IL-1ß, IL-6, IFN-Î³, and TNF-α) along with elevated levels of the anti-inflammatory cytokine IL-10, marked lymphopenia, and elevated neutrophil-to-lymphocyte ratios. Based on the available evidence, we propose a mechanism wherein SARS-CoV-2 infection induces direct organ damage while also fueling an IL-6-mediated cytokine release syndrome (CRS) and hypoxia, resulting in escalating systemic inflammation, multi-organ damage, and end-organ failure. Elevated IL-6 and hypoxia together predisposes patients to pulmonary hypertension, and the presence of asymptomatic hypoxia in COVID-19 further compounds this problem. Due to the similar downstream mediators, we discuss the potential synergistic effects and systemic ramifications of SARS-CoV-2 and influenza virus during co-infection, a phenomenon we have termed "COVI-Flu." Additionally, the differences between CRS and cytokine storm are highlighted. Finally, novel management approaches, clinical trials, and therapeutic strategies toward both SARS-CoV-2 and COVI-Flu infection are discussed, highlighting host response optimization and systemic inflammation reduction.

negative: 148. Acute bipolar disorder depression is associated with immune activation Recent studies indicate that immune activation may be an important component of the pathogenesis of bipolar disorder. The study sample consists of 40 patients admitted to the hospital with a diagnosis of acute bipolar depression. Blood samples were drawn at 3 time points: at time of hospital admission, during the acute hospital stay, and at a six month follow-up. Inflammatory markers were measured including C-reactive protein (CRP), Pentraxin 3 (PTX3), and antibodies to infectious agents. The markers in the bipolar depressed patients were studied over the 3 time points and also compared to those in other groups: 60 hospitalized for acute mania; 69 with recent onset psychosis; 246 with multi-episode schizophrenia; 98 with bipolar disorder not selected for mania or depression; and 222 non-psychiatric controls. The bipolar depressed patients had elevated levels of CRP at all 3 time points. The bipolar depressed patients also had elevated levels of PTX3 at hospital admission which were reduced during the hospital stay and at follow-up. The bipolar depressed group also had elevated levels of antibodies to the nucleocapsid protein of the SARS strain of coronavirus, while elevated levels of these antibodies were not found in the other groups. Our study indicates that bipolar disorder depression is associated with immune activation, particularly during acute exacerbations. These findings may lead to the development of new methods of prevention and treatment.

negative: SARS, Xenotransplantation and Bioterrorism: Preventing the Next Epidemic

negative: The scientific literature on Coronaviruses, COVID-19 and its associated safety-related research dimensions: A scientometric analysis and scoping review Abstract The COVID-19 global pandemic has generated an abundance of research quickly following the outbreak. Within only a few months, more than a thousand studies on this topic have already appeared in the scientific literature. In this short review, we analyse the bibliometric aspects of these studies on a macro level, as well as those addressing Coronaviruses in general. Furthermore, through a scoping analysis of the literature on COVID-19, we identify the main safety-related dimensions that these studies have thus far addressed. Our findings show that across various research domains, and apart from the medical and clinical aspects such as the safety of vaccines and treatments, issues related to patient transport safety, occupational safety of healthcare professionals, biosafety of laboratories and facilities, social safety, food safety, and particularly mental/psychological health and domestic safety have thus far attracted most attention of the scientific community in relation to the COVID-19 pandemic. Our analysis also uncovers various potentially significant safety problems caused by this global health emergency which currently have attracted only limited scientific focus but may warrant more attention. These include matters such as cyber safety, economic safety, and supply-chain safety. These findings highlight why, from an academic research perspective, a holistic interdisciplinary approach and a collective scientific effort is required to help understand and mitigate the various safety impacts of this crisis whose implications reach far beyond the bio-medical risks. Such holistic safety-scientific understanding of the COVID-19 crisis can furthermore be instrumental to be better prepared for a future pandemic.

negative: Developing Universal Influenza Vaccines: Hitting the Nail, Not Just on the Head Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines.

negative: COVID-19: Unique public health issues facing Black, Asian and minority ethnic communities Abstract The 2019 coronavirus disease is a serious public health emergency, with serious adverse implications for populations, healthcare systems, and economies globally. Recently, concerns have been raised about possible association between ethnicity, incidence and outcomes of COVID-19 arisen from early government data. In this review, we will explore the possible association using both recent COVID-19 studies and studies of previous pandemics. We call for data on ethnicity to be routinely collected by governments, as part of international collaboration, alongside other patient demographics and further research to robustly determine magnitude of association. Moreover, governments must learn from previous pandemics and recommended strategies to mitigate risks on minority ethnicities due to socioeconomic disadvantages.

negative: Modeling the Spread and Outbreak Dynamics of Avian Influenza (H5N1) Virus and Its Possible Control Avian Influenza, commonly known as Bird Flu, is an epidemic caused by H5N1 Virus, that primarily affects birds such as chickens, wild water birds, ducks, and swans etc. On rare occasions, pigs and humans will also be affected with this virus In recent years this epidemic has emerged as a major global health concern. The present chapter is aimed at developing mathematical models that predict the spread and outbreak diversity of low pathogenic avian influenza virus. Essentially, we present (1) a deterministic mathematical model which deals with the dynamics of human infection by avian influenza both in birds and in human, (2) a discrete dynamical model for the spread of H5N1, and (3) the statistical transmission model of bird flu taking into account the factors that affect the epidemic transmission such as source of infection and social and natural factors.

negative: Seasonal Variation of Newly Notified Pulmonary Tuberculosis Cases from 2004 to 2013 in Wuhan, China BACKGROUND: Although there was a report about the seasonal variation in Wuhan city, it only analyzed the prevalence data of pulmonary tuberculosis (TB) cases, and just studied the seasonality by subgroup of smear positive and negative from 2006 to 2010 by spectral analysis. In this study, we investigated the seasonality of the total newly notified pulmonary TB cases by subgroups such as time period, sex, age, occupation, district, and sputum smear result from 2004 to 2013 in Wuhan by a popular seasonal adjustment model (TRAMO-SEATS). METHODS: Monthly pulmonary TB cases from 2004 to 2013 in Wuhan were analyzed by the TRAMO-SEATS seasonal adjustment program. Seasonal amplitude was calculated and compared within the subgroups. RESULTS: From 2004 to 2013, there were 77.76 thousand newly notified pulmonary TB cases in Wuhan, China. There was a dominant peak spring peak (March) with seasonal amplitude of 56.81% and a second summer peak (September) of 43.40%, compared with the trough month (December). The spring seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences for spring seasonal amplitude within subgroups of gender, age, district, and sputum smear result (P>0.05). However, there were significant differences in spring seasonal amplitude by occupation, with amplitude ranging from 59.37% to 113.22% (P<0.05). The summer seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences in summer seasonal amplitude within subgroups of gender, district, sputum smear result(P>0.05). There were significant differences in summer seasonal amplitude by age, with amplitude ranging from 36.05% to 100.09% (P<0.05). Also, there were significant differences in summer seasonal amplitude by occupation, with amplitude ranging from 43.40% to 109.88% (P<0.05). CONCLUSIONS: There was an apparent seasonal variation in pulmonary TB cases in Wuhan. We speculated that spring peak in our study was most likely caused by the increased reactivation of the latent TB due to vitamin D deficiency and high PM2.5 concentration, while the summer peak was mainly resulted from the enhanced winter transmission due to indoor crowding in winter, overcrowding of public transportation over the period of the Spring Festival and health care seeking delay in winter.

negative: Models of epidemics: when contact repetition and clustering should be included BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.

negative: Ischemia-reperfusion Injury of the Lung: Role of Surfactant

negative: A Novel Strategy for Bitter Taste Masking of Gankeshuangqing Dispersible Tablets Based on Particle Coating Technology BACKGROUND: Currently, acute upper respiratory tract infections (AURTIs) are increasingly becoming a significant health burden. Gankeshuangqing dispersible tablets (GKSQDT) which have a good effect on treating AURTIs. GKSQDT is composed of baicalin and andrographolide. However, its severe bitterness limits application of patients. Due to the addition of plentiful accessories, common masking methods are unsuitable for GKSQDT. It is thus necessary to develop a new masking method. MATERIALS AND METHODS: The Previous study showed that baicalin was less bitter than andrographolide. Thus, particle coating technology was adapted to prepare composite particles that baicalin coated on the surface of andrographolide to decrease bitterness. Initially, particle size of baicalin and coating time of composite was investigated to prepare composite. Then, scanning electron microscopy, wettability, and infrared (IR) spectrogram were used to characterize the microstructure of composite. Furthermore, electronic tongue test, animal preference experiment, and human sensory test were applied to evaluate the masking effect. RESULTS: To produce composite, baicalin should be ground in vibromill for 6 min. Then, andrographolide fine powder was added to grind together for 6 min. Contact angle of composite was smaller than mixture, and more similar to baicalin. Other physical characterization including microstructure, wettability, and IR also suggested that andrographolide was successfully coated by baicalin superfine. Furthermore, taste-masking test indicated taste-masked tablets was less bitter than original tablets. CONCLUSION: The study indicated that particle coating technology can be used for taste masking of GKSQDT without adding other substance. Moreover, it provides a new strategy of taste masking for national medicine. SUMMARY: A new strategy to mask bitterness without adding any other substance based on coating technology was provided. The masking effect was confirmed by electronic tongue test, animal preference experiment and human sensory test. Abbreviations used: AURTIs: Acute Upper Respiratory Tract Infections; GSQDT: Gankeshuangqing Dispersible Tablets; IR: Infrared Spectrogram; LHPC: Low-substituted Hydroxypropyl Cellulose; CAs: Contact Angles; FTIR: Fourier Transform Infrared Spectra.

negative: Multiplex PCR tests sentinel the appearance of pandemic influenza viruses including H1N1 swine influenza BACKGROUND: Since the turn of the century seven new respiratory viruses have infected man and two of these have resulted in worldwide epidemics. Both SARS Coronavirus which quickly spread to 29 countries in February 2003 and H1N1 swine influenza that recently spread from Mexico to 30 countries in three weeks represent major pandemic threats for mankind. Diagnostic assays are required to detect novel influenza strains with pandemic potential. OBJECTIVE: In this report we evaluate the ability of a multiplex PCR test (xTAG(™)RVP) to detect new, “non-seasonal” influenza viruses including the H1N1 swine influenza A/swine/California/04/2009. STUDY DESIGN: Laboratory based study using retrospective and prospective specimens. RESULTS: This multiplex PCR test detected the present of non-seasonal (non-H1, non-H3) influenza in 20 of 20 patients infected with H1N1 swine flu virus. In addition to detecting the current swine flu the xTAG(™) RVP test detected the H5N1 A/Vietnam/1203/2004 high pathogenicity avian influenza virus that circulated in South East Asia in 2003 as well as 17 out of 17 influenza A viruses representing 11 HA subtypes isolated from birds, swine and horses not yet seen in the human population. CONCLUSION: Based on these results we believe that this molecular test can perform an important role as a sentinel test to detect novel non-seasonal influenza A viruses in patients presenting with influenza-like illness (ILI) and therefore act as an early warning system for the detection of future pandemic influenza threats.

negative: Pandemics and methodological developments in epidemiology history • Catastrophic pandemics since the 17(th) century appear to have spurred innovative methods, concepts, and institutions in epidemiology; • The plague, cholera, tuberculosis, influenza, and HIV/AIDS left a longstanding imprints on epidemiologic methods and concepts; • Pandemics may generate an urgent need for methods that overcome the inadequacy of older methods; • Covid-19 specific contribution could be a greater understanding of population thinking beyond academic and professional circles.

negative: Chinese hesitancy on avian flu The time has come for China to start pulling its weight as a participant in the global response to bird flu — and to learn to collaborate more openly.

negative: Structural and Functional Bases for Broad-Spectrum Neutralization of Avian and Human Influenza A Viruses Influenza virus remains a constant public health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Monoclonal antibody (mAb)-based immunotherapy is a promising strategy for disease control. Here we use a human Ab phage display library and H5 hemagglutinin (HA) ectodomain to select ten neutralizing mAbs (nAbs) with a remarkably broad range among Group 1 influenza viruses, including the H5N1 “bird flu” and the H1N1 “Spanish flu” strains. Notably, nine of the Abs utilize the same germline gene, VH1-69. The crystal structure of one mAb bound to H5N1 HA reveals that only the heavy chain inserts into a highly conserved pocket in the HA stem, inhibiting the conformational changes required for membrane fusion. Our studies indicate that nAbs targeting this pocket could provide broad protection against both seasonal and pandemic influenza A infections.

negative: A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918 BACKGROUND: The H1N1 influenza A virus has been circulating in the human population for over 95 years, first manifesting itself in the pandemic of 1917–1918. Initial mortality was extremely high, but dropped exponentially over time. Influenza viruses have high mutation rates, and H1N1 has undergone significant genetic changes since 1918. The exact nature of H1N1 mutation accumulation over time has not been fully explored. METHODS: We have made a comprehensive historical analysis of mutational changes within H1N1 by examining over 4100 fully-sequenced H1N1 genomes. This has allowed us to examine the genetic changes arising within H1N1 from 1918 to the present. RESULTS: We document multiple extinction events, including the previously known extinction of the human H1N1 lineage in the 1950s, and an apparent second extinction of the human H1N1 lineage in 2009. These extinctions appear to be due to a continuous accumulation of mutations. At the time of its disappearance in 2009, the human H1N1 lineage had accumulated over 1400 point mutations (more than 10% of the genome), including approximately 330 non-synonymous changes (7.4% of all codons). The accumulation of both point mutations and non-synonymous amino acid changes occurred at constant rates (μ = 14.4 and 2.4 new mutations/year, respectively), and mutations accumulated uniformly across the entire influenza genome. We observed a continuous erosion over time of codon-specificity in H1N1, including a shift away from host (human, swine, and bird [duck]) codon preference patterns. CONCLUSIONS: While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution.

negative: Ingestion of Exopolymers from Aureobasidium pullulans Reduces the Duration of Cold and Flu Symptoms: A Randomized, Placebo-Controlled Intervention Study AIM: The objective of the study was to assess the efficacy of exopolymers from Aureobasidium pullulans (EAP) on the incidence of colds and flu in healthy adults. METHODS: We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 76 subjects (30–70 years of age) were recruited from the general population. The subjects were instructed to take one capsule per day of either EAP or a placebo for a period of 8 weeks. The duration of cold and flu symptoms, a primary variable in assessing effectiveness, and serum cytokine levels as well as WBC counts as secondary variables were also evaluated. RESULTS: EAP was associated with a statistically significant decrease in the duration of cold and flu symptoms, a primary variable in assessing effectiveness. Although cold and flu symptom levels were not significantly different at a significance level of 5%, the cold and flu symptom levels of the EAP group were less severe compared to the placebo group. No statistically significant changes of serum cytokine levels as well as WBC counts were observed. CONCLUSION: The results showed that EAP is a useful pharmaceutical and functional food material for preventing and treating colds and flu.

negative: Viral Respiratory Infections Diagnosed by Multiplex PCR after Allogeneic Hematopoietic Stem Cell Transplantation: Long-Term Incidence and Outcome Abstract Viral respiratory infections (VRIs) are frequent after hematopoietic stem cell transplantation and constitute a potential cause of mortality. We analyzed the incidence, risk factors, and prognosis of VRIs in a cohort of transplanted patients. More frequent viruses were human coronavirus and human rhinovirus followed by flu-like viruses and adenovirus. Risk factors for death were lymphocytopenia and high steroid dosage.

negative: Influenza in long‐term care facilities Long‐term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long‐term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence.

negative: Media, social proximity, and risk: a comparative analysis of newspaper coverage of Avian Flu in Hong Kong and in the United States. This study uses the psychometric paradigm (Renn & Rohrmann, 2000; Slovic, 1992) as an analytic framework to analyze the risk dimensions being conveyed in media coverage of Avian flu in Hong Kong and in the United States between 2003 and 2007. A quantitative content analysis of The New York Times and South China Morning Post stories showed different patterns of avian flu related risk content coverage. The differences revealed that dimensions related to dreadfulness, catastrophic potential, uncertainty, and unfamiliarity were more emphasized in The New York Times than in South China Morning Post. The authors discuss the implications.

negative: The Perfect Storm: Coronavirus (Covid-19) Pandemic Meets Overfat Pandemic

negative: Coronaviruses and SARS-CoV-2: A Brief Overview In late December 2019, several cases of pneumonia of unknown origin were reported from China, which in early January 2020 were announced to be caused by a novel coronavirus. The virus was later denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined as the causal agent of Coronavirus Disease 2019 (COVID-19). Despite massive attempts to contain the disease in China, the virus has spread globally, and COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. Here we provide a short background on coronaviruses, and describe in more detail the novel SARS-CoV-2 and attempts to identify effective therapies against COVID-19.

negative: Extensive multiplex PCR diagnostics reveal new insights into the epidemiology of viral respiratory infections Viral respiratory infections continue to pose a major global healthcare burden. At the community level, the co-circulation of respiratory viruses is common and yet studies generally focus on single aetiologies. We conducted the first comprehensive epidemiological analysis to encompass all major respiratory viruses in a single population. Using extensive multiplex PCR diagnostic data generated by the largest NHS board in Scotland, we analysed 44230 patient episodes of respiratory illness that were simultaneously tested for 11 virus groups between 2005 and 2013, spanning the 2009 influenza A pandemic. We measured viral infection prevalence, described co-infections, and identified factors independently associated with viral infection using multivariable logistic regression. Our study provides baseline measures and reveals new insights that will direct future research into the epidemiological consequences of virus co-circulation. In particular, our study shows that (i) human coronavirus infections are more common during influenza seasons and in co-infections than previously recognized, (ii) factors associated with co-infection differ from those associated with viral infection overall, (iii) virus prevalence has increased over time especially in infants aged <1 year, and (iv) viral infection risk is greater in the post-2009 pandemic era, likely reflecting a widespread change in the viral population that warrants further investigation.

negative: Seasonal variations of respiratory viruses and etiology of human rhinovirus infection in children Abstract Background Using the polymerase chain reaction (PCR) method it is possible to detect uncultivable viruses and discover multiple viral infections. However, the clinical importance of these findings in relation to symptoms is not known. Objectives The seasonal fluctuations of respiratory viruses and the clinical outcomes of single infections and dual infections were investigated. Study design Nasal aspirate samples were obtained from outpatients and inpatients of a children’s hospital and these samples were subjected to real-time PCR to detect 16 respiratory viruses. Seasonal variations of the 16 viruses and the clinical outcomes such as wheezing, the need for oxygenation and prolonged hospitalization of patients with single viral infections and multiple infections were determined for the 5 most often detected viruses. Results Among 512 specimens analyzed, one or more viruses were detected in 424 (83%) specimens. Two or more viruses were detected in 160 samples (31% of all samples). The epidemic peaks of the viruses did not coincide with each other. Rhinoviruses were the most frequently detected viruses and their coinfection rates were also higher. However, the disease severity in the lower respiratory tract did not differ in most respiratory viral infections regardless of whether there was single infection or dual infection with a rhinovirus and other respiratory virus. Conclusions Seasonal distribution was seen for each virus. There were no significant differences in clinical symptoms in the children studied. Because the infection of rhinoviruses is the common occurrence in children, it is hypothesized that the factors related to disease severity are mainly the underlying conditions of the children.

negative: Patient-Based Transcriptome-Wide Analysis Identify Interferon and Ubiquination Pathways as Potential Predictors of Influenza A Disease Severity BACKGROUND: The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions. METHODOLOGY/PRINCIPAL FINDINGS: Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis. CONCLUSION/SIGNIFICANCES: The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.

negative: Brief Report: Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection. BACKGROUND Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period. METHODS We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome coronavirus, using data from the epidemic in 2003 in Hong Kong. RESULTS We estimated the incubation period of severe acute respiratory syndrome based on a subset of patients with available data on exposure periods and a separate subset of patients in a putative common source outbreak, and we found associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders. CONCLUSIONS Our findings suggest that patients with a shorter incubation period went on to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association.

negative: Does COVID-19 infection impact on the trend of seasonal influenza infection? 11 countries and regions, from 2014 to 2020 OBJECTIVES: Infection due to the 2019 novel coronavirus disease (COVID-19) is dramatically widespread around the world. The COVID-19 pandemic could increase public concern to prevent infectious disease. The present study aimed to assess the relationship between the COVID-19 epidemic and the potential decrease in seasonal influenza cases. METHODS: This study was performed to show trends in seasonal influenza cases from the 2014-2015 season to the 2019-2020 season in 11 countries and regions, and evaluate whether the trends in the 2019-2020 season were different before and after the COVID-19 pandemic compared to previous seasons using a quasi-experimental difference-in-difference design. RESULTS: In East Asia, the number of seasonal influenza cases in the 2019-20 season was lower after the COVID-19 transmission compared to previous years. However, this was not the case in American countries or in European countries. CONCLUSION: The COVID-19 epidemic might have altered health behaviors, resulting in an unexpected reduction of seasonal influenza cases.

negative: Mutated COVID-19, May Foretells Mankind in a Great Risk in the Future Corona virus disease 2019 SARS-CoV-2 (COVID-19) is a zoonotic virus causing a variety of severe of respiratory diseases. SARS-CoV-2 is closest to SARS-CoV and MERS-CoV in structure. The highly prevalence of COVID-19 is due to the lack onset of symptoms. Our study aimed to present an overview of the virus in terms of structure, epidemiology, symptoms, treatment, and prevention. Conduct the differences of whole genome sequence and some viral proteins to determine the gap and the change alternation of nucleotides and amino acids sequences. We evaluate 11 complete genome sequence of different coronavirus using BAST and MAFFT software. We also selected 7 types of structural proteins. We were conclude that COVID-19 might be created new mutations specifically in glycoproteins hence requires caution and complete preparation by health authorities.

negative: Dynamics of translation by single ribosomes through mRNA secondary structures During protein synthesis, the ribosome translates nucleotide triplets in single-stranded mRNA into polypeptide sequences. Strong downstream mRNA secondary (2°) structures, which must be unfolded for translation, can slow or even halt protein synthesis. Here we employ single molecule fluorescence resonance energy transfer to determine reaction rates for specific steps within the elongation cycle as the Escherichia coli ribosome encounters stem loop or pseudoknot mRNA 2° structures. Downstream stem-loops containing 100% G-C base pairs decrease the rates of both tRNA translocation within the ribosome and deacylated tRNA dissociation from the ribosomal exit (E) site. Downstream stem-loops or pseudoknots containing both G-C and A-U pairs also decrease the rate of tRNA dissociation, but they have little effect on tRNA translocation rate. Thus, somewhat surprisingly, unfolding of mRNA 2° structures is more closely coupled to E-site tRNA dissociation than to tRNA translocation.

negative: Epidemiological data from the COVID-19 outbreak, real-time case information Cases of a novel coronavirus were first reported in Wuhan, Hubei province, China, in December 2019 and have since spread across the world. Epidemiological studies have indicated human-to-human transmission in China and elsewhere. To aid the analysis and tracking of the COVID-19 epidemic we collected and curated individual-level data from national, provincial, and municipal health reports, as well as additional information from online reports. All data are geo-coded and, where available, include symptoms, key dates (date of onset, admission, and confirmation), and travel history. The generation of detailed, real-time, and robust data for emerging disease outbreaks is important and can help to generate robust evidence that will support and inform public health decision making.

negative: Transmission routes of 2019-nCoV and controls in dental practice A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

negative: Comparison of Luminex xTAG® RVP fast assay and real time RT‐PCR for the detection of respiratory viruses in adults with community‐acquired pneumonia Community‐acquired pneumonia (CAP) is the third cause of death worldwide. Viruses are frequently detected in adult CAP. Highly sensitive diagnostic techniques should be used due to poor viral shedding. Different sampling methods can affect viral detection, being necessary to establish the optimal type of sample for identifying respiratory viruses in adults. The detection rates of respiratory viruses by Luminex xTAG® RVP fast assay, real time RT‐PCR (rtRT‐PCR) (Sacace®), and immunofluorescence assay (IFA) in adult CAP were performed in nasopharyngeal swabs (NPS) and aspirates (NPA) from 179 hospitalized adults. Positivity was 47.5% for Luminex®, 42.5% for rtRT‐PCR (P = 0.3), and 2.7% for IFA (2.7%) (P < 0.0). The sensitivity, specificity, and kappa coefficient of xTAG® RVP compared with rtRT‐PCR were 84.2%, 79.6%, and 0.62%, respectively. Luminex® and rtRT‐PCR detected 65 (58.0%) and 57 (50.9%) viruses in 112 NPA and 35 (34.3%) and 31 (30.4%) in 102 NPS, respectively (P < 0.01). xTAG® RVP is appropriate for detecting respiratory viruses in CAP adults. Both molecular techniques yielded better results with nasopharyngeal aspirate than swabs. J. Med. Virol. 88:1173–1179, 2016. © 2016 Wiley Periodicals, Inc.

negative: The impact of communications about swine flu (influenza A H1N1v) on public responses to the outbreak: results from 36 national telephone surveys in the UK. OBJECTIVES To assess the association between levels of worry about the possibility of catching swine flu and the volume of media reporting about it; the role of psychological factors in predicting likely uptake of the swine flu vaccine; and the role of media coverage and advertising in predicting other swine flu-related behaviours. DESIGN Data from a series of random-digit-dial telephone surveys were analysed. A time series analysis tested the association between levels of worry and the volume of media reporting on the start day of each survey. Cross-sectional regression analyses assessed the relationships between likely vaccine uptake or behaviour and predictor variables. SETTING Thirty-six surveys were run at, on average, weekly intervals across the UK between 1 May 2009 and 10 January 2010. Five surveys (run between 14 August and 13 September) were used to assess likely vaccine uptake. Five surveys (1-17 May) provided data relating to other behaviours. PARTICIPANTS Between 1047 and 1173 people aged 16 years or over took part in each survey: 5175 participants provided data about their likely uptake of the swine flu vaccine; 5419 participants provided data relating to other behaviours. MAIN OUTCOME MEASURES All participants were asked to state how worried they were about the possibility of personally catching swine flu. Subsets were asked how likely they were to take up a swine flu vaccination if offered it and whether they had recently carried tissues with them, bought sanitising hand gel, avoided using public transport or had been to see a general practitioner, visited a hospital or called NHS Direct for a flu-related reason. RESULTS The percentage of 'very' or 'fairly' worried participants fluctuated between 9.6% and 32.9%. This figure was associated with the volume of media reporting, even after adjusting for the changing severity of the outbreak [chi2(1) = 6.6, p = 0.010, coefficient for log-transformed data = 2.6]. However, this effect only occurred during the UK's first summer wave of swine flu. In total, 56.1% of respondents were very or fairly likely to accept the swine flu vaccine. The strongest predictors were being very worried about the possibility of oneself [adjusted odds ratio (aOR) 4.7, 95% confidence interval (CI) 3.2 to 7.0] or one's child (aOR 8.0, 95% CI 4.6 to 13.9) catching swine flu. Overall, 33.1% of participants reporting carrying tissues with them, 9.5% had bought sanitising gel, 2.0% had avoided public transport and 1.6% had sought medical advice. Exposure to media coverage or advertising about swine flu increased tissue carrying or buying of sanitising hand gel, and reduced avoidance of public transport or consultation with health services during early May 2009. Path analyses showed that media coverage and advertising had these differential effects because they raised the perceived efficacy of hygiene behaviours but decreased the perceived efficacy of avoidance behaviours. CONCLUSIONS During the swine flu outbreak, uptake rates for protective behaviours and likely acceptance rates for vaccination were low. One reason for this may in part be explained by was the low level of public worry about the possibility of catching swine flu. When levels of worry are generally low, acting to increase the volume of mass media and advertising coverage is likely to increase the perceived efficacy of recommended behaviours, which, in turn, is likely to increase their uptake.

negative: A review of cardiac manifestations and predictors of outcome in patients with COVID – 19 Abstract Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196, 000 deaths, with more than 50, 000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.

negative: Riding the Shi: From Infection Barriers to the Microbial City How can a microbial approach to global health security protect life? Contemporary infection control mechanisms set the human and the pathogenic microbe against each other, as the victim versus the menace. This biomedical polarization persistently runs through the contemporary dominant mode of thinking about public health and infectious disease governance. Taking its cue from the currently accepted germ theory of disease, such mechanisms render a global city like Hong Kong not only pervasively “on alert” and under threat of unpredictable and pathogenic viruses and other microbes, it also gives rise to a hygiene and antimicrobial politics that is never entirely able to control pathogenic circulation. The article draws on recent advances in medical microbiology, which depart from germ theory, to invoke an ecological understanding of the human-microbe relation. Here, while a small number of viruses are pathogenic, the majority are benign; some are even essential to human life. Disease is not just the outcome of a pathogenic microbe infecting a human host but emerges from socioeconomic relations, which exacerbate human-animal-microbial interactions. In a final step, the article draws on Daoist thought to reflect on the ways that such a microbial understanding translates into life and city dwelling.

negative: Middle East Respiratory Syndrome Coronavirus. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging infectious disease that can present with flu-like symptoms. In individuals with comorbidities or who are immunosuppressed, it can be deadly. The disease is transmitted through contact with someone who has MERS-CoV. The occupational health nurse must be cognizant of and educate the workforce about MERS-CoV transmission, prevention, and treatment.

negative: Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) In late December 2019, a cluster of cases with 2019 Novel Coronavirus pneumonia (SARS-CoV-2) in Wuhan, China, aroused worldwide concern. Previous studies have reported epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19). The purpose of this brief review is to summarize those published studies as of late February 2020 on the clinical features, symptoms, complications, and treatments of COVID-19 and help provide guidance for frontline medical staff in the clinical management of this outbreak.

negative: Two mechanisms for accelerated diffusion of COVID-19 outbreaks in regions with high intensity of population and polluting industrialization: the air pollution-to-human and human-to-human transmission dynamics What is COVID-19? Coronavirus disease 2019 (COVID-19) is viral infection that generates a severe acute respiratory syndrome with serious pneumonia that may result in progressive respiratory failure and death. What are the goals of this investigation? This study explains the geo-environmental determinants of the accelerated diffusion of COVID-19 in Italy that is generating a high level of deaths and suggests general lessons learned for a strategy to cope with future epidemics similar to COVID-19 to reduce viral infectivity and negative impacts in economic systems and society. What are the results of this study? The main results are: o The accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution. o Hinterland cities have average days of exceeding the limits set for PM10 (particulate matter 10 micrometers or less in diameter) equal to 80 days, and an average number of infected more than 2,000 individuals as of April 1st, 2020, coastal cities have days of exceeding the limits set for PM10 equal to 60 days and have about 700 infected in average. o Cities that average number of 125 days exceeding the limits set for PM10, last year, they have an average number of infected individual higher than 3,200 units, whereas cities having less than 100 days (average number of 48 days) exceeding the limits set for PM10, they have an average number of about 900 infected individuals. o The results reveal that accelerated transmission dynamics of COVID-19 in specific environments is due to two mechanisms given by: air pollution-to-human transmission and human-to-human transmission; in particular, the mechanisms of air pollution-to-human transmission play a critical role rather than human-to-human transmission. o The finding here suggests that to minimize future epidemic similar to COVID-19, the max number of days per year in which cities can exceed the limits set for PM10 or for ozone, considering their meteorological condition, is less than 50 days. After this critical threshold, the analytical output here suggests that environmental inconsistencies because of the combination between air pollution and meteorological conditions (with high moisture%, low wind speed and fog) trigger a take-off of viral infectivity (accelerated epidemic diffusion) with damages for health of population, economy and society. What is a socioeconomic strategy to prevent future epidemics similar to COVID-19? Considering the complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity, lessons learned for COVID-19 have to be applied for a proactive socioeconomic strategy to cope with future epidemics, especially an environmental policy based on reduction of air pollution mainly in hinterland zones of countries, having low wind speed, high percentage of moisture and fog that create an environment that can damage immune system of people and foster a fast transmission of viral infectivity similar to the COVID-19. This study must conclude that a strategy to prevent future epidemics similar to COVID 19 has also to be designed in environmental and sustainability science and not only in terms of biology.

negative: Flu or a Bug? Of late, apart from the four calendar seasons, there is yet another season referred to as the “flu season.” During this time of the year, we routinely hear the phrase “the flu is going around.” I was surprised last week when I heard my 6-year-old son mention to me that there is some bug going around in his class and that his best friend was sick. I asked him to define the bug and he said it causes stuffy nose. The word “bug” is used so callously by adults that it has been registered wrongly in the minds of the little ones.

negative: Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9) Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility.

negative: Modeling the impact of twitter on influenza epidemics. Influenza remains a serious public-health problem worldwide. The rising popularity and scale of social networking sites such as Twitter may play an important role in detecting, affecting, and predicting influenza epidemics. In this paper, we develop a simple mathematical model including the dynamics of ``tweets'' --- short, 140-character Twitter messages that may enhance the awareness of disease, change individual's behavior, and reduce the transmission of disease among a population during an influenza season. We analyze the model by deriving the basic reproductive number and proving the stability of the steady states. A Hopf bifurcation occurs when a threshold curve is crossed, which suggests the possibility of multiple outbreaks of influenza. We also perform numerical simulations, conduct sensitivity test on a few parameters related to tweets, and compare modeling predictions with surveillance data of influenza-like illness reported cases and the percentage of tweets self-reporting flu during the 2009 H1N1 flu outbreak in England and Wales. These results show that social media programs like Twitter may serve as a good indicator of seasonal influenza epidemics and influence the emergence and spread of the disease.

negative: Seasonal Influenza Activity During the SARS-CoV-2 Outbreak in Japan

negative: Novel Coronavirus (COVID‐19) Epidemic: What Are the Risks for Older Patients?

negative: A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo.

negative: Meteorological factors correlate with transmission of 2019-nCoV: Proof of incidence of novel coronavirus pneumonia in Hubei Province, China Objective: many potential factors contribute to the outbreak of COVID-19.It aims to explore the effects of various meteorological factors on the incidence of COVID-19. Methods: Taking Hubei province of China as an example, where COVID-19 was first reported and there were the most cases, we collected 53 days of confirmed cases (total 67773 cases) and ten meteorological parameters up to March 10. Correlation analysis and linear regression were used to judge the relationship of meteorological factors and increment of COVID-19 confirmed cases. Results: Under 95% CI, the increment of confirmed cases in Hubei were correlated with four meteorological parameters of average pressure, average temperature, minimum temperature and average water vapor pressure (equivalent to absolute humidity).The average pressure was positively correlated with the increment (r=+0.358).The negative correlations included average temperature (r=-0.306), minimum temperature (r=-0.347), and average water vapor pressure (r=-0.326). The linear regression results show if minimum temperature increases by 1℃, the incremental confirmed cases in Hubei decreases by 72.470 units on average. Conclusion: Statistically, the incidence of COVID-19 was correlated with average pressure, average temperature, minimum temperature and average water vapor pressure. It is positively correlated with the average pressure and negatively correlated with the other three parameters. Compared with relative humidity, 2019-nCov is more sensitive to water vapor pressure. The reason why the epidemic situation in Hubei expanded rapidly is significantly related to the climate characteristics of low temperature and dryness of Hubei in winter.

negative: COVID-19 outbreak: less stethoscope, more ultrasound

negative: Increased Detection of Viruses in Children with Respiratory Tract Infection Using PCR Respiratory viruses are a common cause of respiratory tract infection (RTI), particularly in neonates and children. Rapid and accurate diagnosis of viral infections could improve clinical outcomes and reduce the use of antibiotics and treatment sessions. Advances in diagnostic technology contribute to the accurate detection of viruses. We performed a multiplex real-time polymerase chain reaction (PCR) to investigate the viral etiology in pediatric patients and compared the detection rates with those determined using traditional antigen tests and virus cultures. Fifteen respiratory viruses were included in our investigation: respiratory syncytial virus A/B (RSV), influenza virus A (FluA) and influenza virus B (FluB), human metapneumovirus (MPV), enterovirus (EV), human parainfluenza virus (PIV) types 1–4, human rhinovirus (RV), human coronavirus OC43, NL63, and 229E, human adenovirus (ADV), and human bocavirus (Boca). In total, 474 specimens were collected and tested. Respiratory viruses were detected more frequently by PCR (357, 75.3%) than they were by traditional tests (229, 49.3%). The leading pathogens were RSV (113, 23.8%), RV (72, 15.2%), PIV3 (53, 11.2%), FluA (51, 10.8%), and ADV (48, 10.1%). For children younger than 5 years, RSV and RV were most prevalent; for children older than 5 years, FluA and ADV were the most frequently detected. Of the specimens, 25.8% (92/357) were coinfected with two or more viruses. RV, Boca, PIV2, FluB, and PIV4 had higher rates of coinfection; MPV and PIV1 had the lowest rates of coinfection (9.1% and 5.3%). To conclude, the detection power of PCR was better than that of traditional antigen tests and virus cultures when considering the detection of respiratory viruses. RSV and RV were the leading viral pathogens identified in the respiratory specimens. One-quarter of the positive specimens were coinfected with two or more viruses. In the future, further application of PCR may contribute to the rapid and accurate diagnosis of respiratory viruses and could improve patient outcomes.

negative: Common Cold and Flu Most of the causative agents of the common cold are viruses. The respiratory system consists of an air conduction portion and a respiratory portion. The direct initiating factor of the common cold is low temperature, especially relative coldness. When people feel cold or chilly, vascular constriction around the inlet area of air occurs, resulting in a reduction of mucus secretion containing various antiviral soluble mediators and followed by an explosive increase in the nasal viral flora. A relatively low temperature and dryness are good conditions for viral proliferation and invasion to the body. The first symptom of the common cold is usually a runny nose, followed by a sore throat and/or systemic fever. Acute symptoms of the common cold are usually terminated within 3 days, at the longest 5~7 days. The mortality rate of severe acute respiratory syndrome (SARS) has reached around 10%. A novel swine-origin influenza A (H1N1) virus caused the occurrence of more than 130,000 patients and dead cases of more than 800 people. H5N1 avian influenza showed an extremely high mortality rate, even though its infectivity is low. A new serotype of AI (H7N9) has appeared in some areas of China. Vitamin C can prevent the onset of a cold. Vitamin C can even prevent influenza virus from spreading down from the upper respiratory tract to the lower one. In addition, levels of interferon (IFN) in the bronchoalveolar lavage (BAL) fluid are markedly low in vitamin C-insufficient mice. Inflammatory cells are markedly increased in BAL fluid, providing the immunological evidences that daily supplementation of high-dose vitamin C can prevent influenza infection and that, in extreme case, it can save the life.

negative: Mapping the Landscape of Artificial Intelligence Applications against COVID-19 COVID-19, the disease caused by the SARS-CoV-2 virus, has been declared a pandemic by the World Health Organization, with over 2.5 million confirmed cases as of April 23, 2020. In this review, we present an overview of recent studies using Machine Learning and, more broadly, Artificial Intelligence, to tackle many aspects of the COVID-19 crisis at different scales including molecular, clinical, and societal applications. We also review datasets, tools, and resources needed to facilitate AI research. Finally, we discuss strategic considerations related to the operational implementation of projects, multidisciplinary partnerships, and open science. We highlight the need for international cooperation to maximize the potential of AI in this and future pandemics.

negative: Respiratory and ventilator management of COVID-19. The current pandemic of COVID-19 has infected around 2.5 million people with more than 125,000 deaths across the globe till date, and numbers are still rising. The causative organism is a virus of corona family. The International Committee on Taxonomy of Viruses (ICTV) named it severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to its similarities with the virus was caused SARS outbreak (SARS-CoV). Although most of the patients present with less severe symptoms like rhinitis, cough, fever, and mild flu-like symptoms, it may progress to severe acute respiratory illness, pneumonia or acute respiratory distress syndrome (ARDS) mainly in immunocompromised hosts. Severe infections mainly involve lungs, and compromise its capacity of ventilation. Respiratory and mechanical ventilation is one of the important parts of management.

negative: Burden and Risk Factors for Coronavirus Infections in Infants in Rural Nepal BACKGROUND: Knowledge of risk factors for symptomatic human coronavirus (HCoV) infections in children in community settings is limited. We estimated the disease burden and impact of birth-related, maternal, household, and seasonal factors on HCoV infections among children from birth to 6 months old in rural Nepal. METHODS: Prospective, active, weekly surveillance for acute respiratory infections (ARIs) was conducted in infants over a period of 3 years during 2 consecutive, population-based randomized trials of maternal influenza immunization. Midnasal swabs were collected for acute respiratory symptoms and tested for HCoV and other viruses by reverse-transcription polymerase chain reaction. Association between HCoV incidence and potential risk factors was modeled using Poisson regression. RESULTS: Overall, 282 of 3505 (8%) infants experienced an HCoV ARI within the first 6 months of life. HCoV incidence overall was 255.6 (95% confidence interval [CI], 227.3–286.5) per 1000 person-years, and was more than twice as high among nonneonates than among neonates (incidence rate ratio [IRR], 2.53; 95% CI, 1.52–4.21). HCoV ARI incidence was also positively associated with the number of children <5 years of age per room in a household (IRR, 1.13; 95% CI, 1.01–1.28). Of the 296 HCoV infections detected, 46% were coinfections with other respiratory viruses. While HCoVs were detected throughout the study period, seasonal variation was also observed, with incidence peaking in 2 winters (December–February) and 1 autumn (September–November). CONCLUSIONS: HCoV is associated with a substantial proportion of illnesses among young infants in rural Nepal. There is an increased risk of HCoV infection beyond the first month of life.

negative: Does COVID-19 infection impact on the trend of seasonal influenza infection? 11 countries and regions, from 2014 to 2020 Abstract Objectives Infection due to the 2019 novel coronavirus disease (COVID-19) is widespread dramatically around the world. This COVID-19 pandemic could increase public concern to prevent infectious disease. The present study aimed to assess the relationship between the COVID-19 epidemic and decreasing another infectious disease. Methods This study was performed to show trends in seasonal influenza cases from the 2014–2015 season to the 2019–2020 season in 11 countries and regions, and evaluate whether the trends in the 2019–2020 season were different before and after the COVID-19 pandemic compared to previous seasons using a quasi-experimental difference-in-difference design. Results In East Asia, the number of seasonal influenza cases in the 2019–20 season was lower after the COVID-19 transmission compared to previous years. However, this was not the case in the American countries or in European countries. Conclusion The COVID-19 epidemic might have altered health behaviors, resulting in an unexpected reduction of seasonal influenza cases.

negative: Prevalence of major depressive disorder and socio-demographic correlates: Results of a representative household epidemiological survey in Beijing, China Abstract Background Major depressive disorder (MDD) is the most prevalent mental disorder in the general population and has been associated with socioeconomic factors. Beijing has undergone significant socioeconomic changes in last decade, however no large-scale community epidemiological surveys of MDD have been conducted in Beijing since 2003. Aims To determine the prevalence of MDD and its socio-demographic correlates in a representative household sample of the general population in Beijing, China. Method Data were collected from the 2010 representative household epidemiological survey of mental disorders in Beijing. The multistage cluster random sampling method was used to select qualified subjects in 18 districts and counties, and then face-to-face interviews were administered using the Chinese version of Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P) during November 1, 2010 to December 31, 2010. Results 19,874 registered permanent residents were randomly identified and 16,032 (response rate=80.7%) completed face-to-face interviews. The time-point and life-time prevalence rates of MDD were estimated to be 1.10% (95% CI: 0.94–1.26%) and 3.56% (95% CI: 3.27–3.85%) respectively. Significant differences were found in sex, age, location of residence, marital status, education, employment status, personal/family monthly income, perception of family environment and relationship with others, when comparing residents with MDD to those without MDD. Those who were female, aged 45 or above, reported low family income, or reported an “average” or “poor” family environment were associated with a higher risk of MDD. Conclusions The prevalence of MDD reported in this survey is relatively lower than that in other western countries. Female sex, age older than 45, low family income, and poor family environment appear to be independent risk factors for MDD.

negative: Estimates of the Undetected Rate among the SARS-CoV-2 Infected using Testing Data from Iceland Testing for SARS-CoV-2 in the United States is currently targeted to individuals whose symptoms and/or jobs place them at a high presumed risk of infection. An open question is, what is the share of infections that are undetected under current testing guidelines? To answer this question, we turn to COVID-19 testing data from Iceland. The criteria for testing within the Icelandic medical system, processed by the National University Hospital of Iceland (NUHI), have also been targeted at high-risk individuals, but additionally most Icelanders qualify for voluntary testing through the biopharmaceutical company deCODE genetics. We use results from Iceland's two testing programs to estimate the share of infections that are undetected under standard (NUHI) testing guidelines. Because of complications in the deCODE testing regime, it is not possible to estimate a single value for this this undetected rate; however, a range can be estimated. Our primary estimates for the fraction of infections that are undetected range from 88.7% to 93.6%.

negative: Open Data Resources for Fighting COVID-19 We provide an insight into the open data resources pertinent to the study of the spread of Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behaviour, regional mortality rates, and effectiveness of government measures. Open data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, at a world scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 data-sets at a country-wide level (i.e. China, Italy, Spain, France, Germany, U.S., etc.). In an attempt to facilitate the rapid response to the study of the seasonal behaviour of Covid-19, we enumerate the main open resources in terms of weather and climate variables. CONCO-Team: The authors of this paper belong to the CONtrol COvid-19 Team, which is composed of different researches from universities of Spain, Italy, France, Germany, United Kingdom and Argentina. The main goal of CONCO-Team is to develop data-driven methods for the better understanding and control of the pandemic.

negative: Clinical evaluation of viral acute respiratory tract infections in children presenting to the emergency department of a tertiary referral hospital in the Netherlands BACKGROUND: The relative incidence and clinical impact of individual respiratory viruses remains unclear among children presenting to the hospital emergency department with acute respiratory tract infection (ARTI). METHODS: During two winter periods, respiratory virus real-time multiplex PCR results were evaluated from children (< 18 years) presenting to the emergency department of a tertiary referral hospital with ARTI that had been sampled within 48 hours of hospital presentation. In an attempt to identify virus-specific distinguishing clinical features, single virus infections were correlated with presenting signs and symptoms, clinical findings and outcomes using multivariate logistic regression. RESULTS: In total, 274 children with ARTI were evaluated and most were aged < 3 years (236/274, 86%). PCR detected respiratory viruses in 224/274 (81.8%) children and included 162 (59%) single and 62 (23%) mixed virus infections. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) single virus infections were common among children aged < 3 years, but proportional differences compared to older children were only significant for RSV (95% CI 1.3–15). Clinical differentiation between viral ARTIs was not possible due to common shared presenting signs and symptoms and the high frequency of mixed viral infections. We observed virus-associated outcome differences among children aged < 3 years. Oxygen treatment was associated with RSV (OR 3.6) and inversely correlated with FLU (OR 0.05). Treatment with steroids (OR 3.4) or bronchodilators (OR 3.4) was associated with HRV. Severe respiratory complications were associated with HRV (OR 3.5) and inversely correlated with RSV (OR 0.24). CONCLUSIONS: Respiratory viruses are frequently detected in young children presenting to the hospital emergency department with ARTI and require PCR diagnosis since presenting signs and symptoms are not discriminant for a type of virus. RSV and HRV bear a high burden of morbidity in the pediatric clinical setting.

negative: Occurrence and frequency of coronavirus infections in humans as determined by enzyme-linked immunosorbent assay. The occurrence of human coronavirus (HCV) infections was analyzed by using sequential sera taken between 1976 and 1981 from adults working in the London area. Antibody rises to HCV 229E and HCV OC43 group viruses were measured in serum samples from these subjects by enzyme-linked immunosorbent assay. HCV infections were found throughout the year, although most occurred during two periods, from June through September and from December through February. There were no marked seasonal differences in either the range of antibody rises obtained or in the HCV groups to which these antibody rises were directed. However, there were more HCV antibody rises during the summer than in the winter. The antibody duration varied considerably, but had a mean of 3.5 months. Finally, the frequency of HCV infection per person was calculated to be 1 per 7.8 months.

negative: Influenza and COVID-19 coinfection: Report of six cases and review of the literature Coronavirus disease 2019 (COVID-19) pandemic caused infection in a season when influenza is still prevalent. Both viruses have similar transmission characteristics and common clinical manifestations. Influenza has been described to cause respiratory infection with some other respiratory pathogens. However, the information of COVID-19 and influenza coinfection is limited. In this study, we reported our coinfected cases and reviewed the literature. We included all COVID-19 diagnosed patients. All patients with a presumed diagnosis of COVID-19 were routinely screened for influenza. Their thorax radiology was reviewed for COVID-19-influenza differentiation. During the study period, 1103 patients have been diagnosed with COVID-19. Among them, six patients (0.54%) were diagnosed coinfected with influenza. There have been 28 more coinfected patients reported. Laboratory-based screening studies reported more patients. Thorax radiology findings were compatible with COVID-19 in five and with influenza in one of our patients. Our cases were mild to moderate in severity. The reported cases in the literature included patients died (n = 2) and those living ventilator dependent or under mechanical ventilation. COVID-19 and influenza coinfection is rare. Screening studies report more cases, suggesting that unless screening patients with COVID-19, the coinfection remains undiagnosed and underestimated. Increasing experience in thoracic radiology may contribute to diagnose the responsible virus(es) from the clinical illness. Influenza vaccine for larger population groups can be recommended to simplify clinicians' work.

negative: Clinico-epidemiological characteristics of acute respiratory infections by coronavirus OC43, NL63 and 229E Abstract Background and objectives Acute respiratory infection is a very common condition in the general population. The majority of these infections are due to viruses. This study attempted to determine the clinical and epidemiological characteristics of adult patients with respiratory infection by the coronavirus OC43, NL63 and 229E. Patients and methods Between January 2013 and February 2014, we prospectively studied all patients with suspected clinical respiratory infection by taking throat swabs and performing a reverse transcription polymerase chain reaction in search of coronavirus. Results In 48 cases (7.0% of the 686 enrolled patients; 12.6% of the 381 in whom a virus was detected) the presence of a coronavirus demonstrated. In 24 cases, the virus was OC43 (50%); in 14 cases, the virus was NL63 (29%); and in 10 cases, the virus was 229E (21%). The mean age was 54.5 years, with a slight predominance of men. The most common clinical presentations were nonspecific influenza symptoms (43.7%), pneumonia (29.2%) and chronic obstructive pulmonary disease exacerbation (8.3%). Fifty-two percent of the patients required hospitalization, and 2 patients required intensive care. There were no deaths. Conclusion Acute respiratory infections caused by coronavirus mainly affect middle-aged male smokers, who are often affected by previous diseases. The most common clinical picture has been nonspecific influenza symptoms.

negative: Incidence and seasonality of respiratory viruses causing acute respiratory infections in the Northern United Arab Emirates BACKGROUND: The data on the seasonality of respiratory viruses helps to ensure the optimal vaccination period and to monitor the possible outbreaks of variant type. OBJECTIVES: This study was designed to describe the molecular epidemiology and seasonality of acute respiratory infection (ARI)‐related respiratory viruses in the United Arab Emirates (UAE). METHODS: Both upper and lower respiratory specimens were collected for the analysis from all the patients who visited the Sheikh Khalifa Specialty Hospital (SKSH) with ARI for over 2 years. The multiplex real‐time reverse transcription polymerase chain reaction (rRT‐PCR) test was used to detect respiratory viruses, which include human adenovirus, influenza virus (FLU) A and B, respiratory syncytial virus, parainfluenza viruses, human rhinovirus (HRV), human metapneumovirus, human enterovirus, human coronavirus, and human bocavirus. RESULTS: A total of 1,362 respiratory samples were collected from 733 (53.8%) male and 629 (46.2%) female patients with ARI who visited the SKSH between November 2015 and February 2018. The rRT‐PCR test revealed an overall positivity rate of 37.2% (507/1362). The positive rate increased during winter; it was highest in December and lowest in September. FLU was the most frequently detected virus (273/1362 [20.0%]), followed by human rhinovirus (146/1362 [10.7%]). The FLU positivity rate showed two peaks, which occurred in August and December. The peak‐to‐low ratio for FLU was 2.26 (95% confidence interval: 1.52‐3.35). CONCLUSIONS: The pattern of FLU in the UAE parallels to that of temperate countries. The trend of the small peak of FLU in the summer suggests a possibility of semi‐seasonal pattern in the UAE.

negative: Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial BACKGROUND: The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. METHODS: This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. RESULTS: Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. CONCLUSION: A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. TRIAL REGISTRATION: NCT01389518

negative: Human respiratory coronavirus HKU1 versus other coronavirus infections in Italian hospitalised patients Abstract Background Human respiratory coronavirus (hCoV) HKU1 infections were reported for the first time in 2005 in Hong Kong. Objective To investigate epidemiological, clinical, and diagnostic features of HKU1 infections. Study design Longitudinal, prospective study from November 2005 through May 2006 in a hospitalised patient population. Results Overall, 48/426 (11.3%) patients were found to be infected by hCoV acute respiratory tract infections (ARTI). Of these, 10 (19.2%) were caused by HKU1 (6 single infections and 4 coinfections) during the period January–May 2006. Diagnosis was made by using RT-PCR for all four hCoVs, and in parallel, in-house developed group-specific monoclonal antibodies (MAbs) for HKU1 and 229E. HKU1-specific MAb was able to retrospectively identify 8 of 10 HKU1 strains detected by RT-PCR. Phylogenetic analysis showed that four HKU1 strains were genotype A and six genotype B. In HKU1-infected patients, the predominant clinical symptom was rhinorrhea (nine patients). Within group II hCoV, HKU1-infected patients had a significantly lower rate of lower ARTI compared to OC43-infected patients. Conclusion HKU1 hCoV strains circulated in northern Italy during the winter–spring season 2005–2006. Both HKU1 genotypes were detected. HKU1-specific MAb may contribute to the rapid diagnosis of HKU1 infections currently performed by RT-PCR.

negative: Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.

negative: Epidemiology of human coronavirus NL63 infection among hospitalized patients with pneumonia in Taiwan Abstract Background/Purpose Human coronavirus (HCoV) NL63 is recognized in association with upper or lower respiratory tract illnesses in children. This study surveyed the prevalence of HCoV-NL63 and influenza viruses in patients with influenza-like illness in Taiwan during 2010–2011. Methods Throat samples from 107 hospitalized patients with pneumonia and 175 outpatients with influenza-like illness were examined using real-time polymerase chain reaction assays with virus-specific primers, and then virus-positive specimens were confirmed by sequencing the polymerase chain reaction products. Results HCoV-NL63 infection was identified in 8.4% (9/107) of hospitalized patients with pneumonia, but not found in outpatients with influenza-like illness. Age distribution of HCoV-NL63 infection in hospitalized patients with pneumonia indicated that the group aged 16–25 years (20%) had the highest positive rate compared with the other groups, and exhibited a similar age-specific pattern to influenza A/H1N1 infection, but not influenza A/H3N2 and B infections in hospitalized patients. Seasonal prevalence of HCoV-NL63 infection was late winter, overlapping the highest peak of the influenza A/H1N1 epidemic during December 2010 to March 2011 in Taiwan. Co-infection of HCoV-NL63 and influenza A/H1N1 was detected in three hospitalized patients. Clinical manifestation analysis indicated that the main symptoms for HCoV-NL63 infection included fever (88.9%), cough (77.8%), and pneumonia (100%). Co-infection caused significantly higher rates of breathing difficulties, cough, and sore throat than those of single infection with HCoV-NL63 and influenza A/H1N1. Phylogenetic analysis indicated a low level of heterogeneity between Taiwan and global HCoV-NL63 strains. Conclusion Understanding epidemiology of HCoV-NL63 in Taiwan provides an insight for worldwide surveillance of HCoV-NL63 infection.

negative: State-specific influenza vaccination coverage among adults aged > or =18 years--United States, 2003-04 and 2005-06 influenza seasons. Influenza epidemics occur seasonally and result in substantial morbidity and mortality among adults in the United States. Adult groups included in the 2007 Advisory Committee on Immunization Practices (ACIP) recommendation for annual influenza vaccination are persons aged 18-49 years with high-risk conditions (i.e., conditions associated with an increased risk for complications from influenza), persons aged > or =50 years, health-care personnel, and others who are household contacts or caregivers of persons at high risk (e.g., persons with high-risk conditions or children aged < or =59 months). In addition, adults who want to reduce the risk for becoming ill with influenza or of transmitting influenza to others should be vaccinated. Healthy People 2010 (HP2010) objectives include increasing vaccination levels to 90% for adults aged > or =65 years (objective 14-29a) and 60% for persons aged 18-64 years who have one or more high-risk conditions (objective 14-29c). From the 1992-93 through 2003-04 influenza seasons, seasonal influenza vaccination coverage estimates (based on Behavioral Risk Factor Surveillance System [BRFSS] data) among adults aged > or =65 years trended upward, except for three seasons (1997-98, 1999-00, and 2000-01) when no increases occurred (Figure). To evaluate recent state-specific progress toward the HP2010 objectives, CDC compared data from the 2004 and 2006 BRFSS surveys, which reflected vaccinations received during the 2003-04 and 2005-06 influenza seasons; data from the 2004-05 influenza season, which have been published previously, were not included in this comparison because that season was marked by a substantial shortage of influenza vaccine. This report describes the results of the analysis, which indicated that influenza vaccination coverage for the 2005-06 season did not return to levels observed before the vaccine shortage of 2004-05 and remained substantially below HP2010 targets. Comprehensive measures are needed to improve influenza vaccination coverage among adult populations in the United States, including increasing adoption of recommended adult immunization practices by health-care providers, raising public awareness about influenza vaccination, vaccinating throughout the influenza season, and ensuring stable supplies of readily available vaccine.

negative: SARS-CoV-2 detection in patients with influenza-like illness Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei Province, China in late December 2019. We re-analysed 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020 and found that 9 of the 640 throat swabs were positive for SARS-CoV-2 RNA by quantitative PCR, suggesting community transmission of SARS-CoV2 in Wuhan in early January 2020.

negative: Principle and Technology of Dynamic Isolation Based on the reflection on these three misunderstandings for the design of negative pressure isolation ward, as well as a series of experimental studies, both the concept and the effective technology for effective isolation of airborne transmission were formed under the dynamic condition during the common operation of negative pressure isolation ward.

negative: The 2009 pandemic influenza A(H1N1) coincides with changes in the epidemiology of other viral pathogens causing acute respiratory tract infections in children BACKGROUND: In Germany, the outbreak of the novel pandemic 2009 influenza A(H1N1) virus A(H1N1)pdm09 caused a wave of high activity between November 2009 and January 2011. The aim of this study was to investigate the prevalence of 19 respiratory pathogens in children hospitalized for lower respiratory tract infections during the winter influenza seasons of 2009/2010 and 2010/2011 and to observe a possible impact of influenza A(H1N1)pdm09 on the epidemiology of other epidemic viruses. MATERIALS AND METHODS: Specimens were nasopharyngeal aspirates which had been collected from children admitted to the participating hospitals in the area of Mainz, Wiesbaden, and Kiel, Germany, with acute community-acquired lower respiratory tract infections. The specimens were subjected to a previously described multiplex reverse transcription PCR assay to detect the following microorganisms: enterovirus, influenza virus types A and B, respiratory syncytial virus (RSV), parainfluenzavirus types 1–4, adenovirus, Mycoplasma pneumoniae, Chlamydophila pneumoniae, rhinovirus, human metapneumovirus (hMPV), coronavirus OC43 and 229E, influenza A(H1N1)pdm09, Bordetella pertussis, Bordetella parapertussis, and Legionella pneumophila. RESULTS: A total of 3,998 clinical specimens were collected from July 2009 to March 2011, of which 296 were positive for A(H1N1)pdm09. An epidemic of seasonal influenza A or B was not observed in the 2009/2010 season, but a minor epidemic of seasonal influenza B was observed in January/February 2011. Influenza A(H1N1)pdm09 coincided with the absence of the seasonal influenza A of former years. The RSV and hMPV epidemics of 2009/2010 erupted several weeks later than expected based on data collected in the PID-ARI-Network during the past 10 years, whereas in the 2010/2011 influenza season they occurred as expected. CONCLUSIONS: The emergence of the novel influenza A(H1N1)pdm09 virus may have been influenced the epidemiology of other epidemic viruses, such as the RSV and hMPV. No epidemic of seasonal influenza was observed in the 2009/2010 influenza season.

negative: Rapid excess weight loss following laparoscopic gastric bypass leads to increased risk of internal hernia. BACKGROUND Internal hernia (IH) is one of the more acute and potentially devastating complications after laparoscopic gastric bypass (LGB). Currently, there is no way to predict which patients will develop IH. We propose that patients who undergo periods of rapid excess weight loss (EWL) following LGB are more likely to develop IH. METHODS A retrospective review of a prospectively collected laparoscopic gastric bypass database from our bariatric center was performed. Patient data between 2002 and 2009 was reviewed. Demographics, initial body mass index (BMI), detailed weight loss curves, and morbidity, specifically IH, were reviewed. Statistical analysis was performed. Logistic regression analysis was used to obtain an adjusted odds ratio for rapid weight loss and hernia development. RESULTS We reviewed all 934 LGB procedures performed. The average initial BMI was 49.1 kg/m2 (range=34-91 kg/m2). EWL based on our current averages at 1, 3, 6, 9, and 12 months postoperatively were 20, 40, 60, 75, and 85%. We statistically defined rapid EWL as greater than the 90th percentile for weight loss. Rapid EWL was noted in 33.2% (310/934) of patients. Fifty-eight (6.2%) patients were identified with IH. Of these, 27(46.5%) had periods of rapid EWL (odds ratio [OR]=1.83; 95% CI=1.07, 3.02). Bivariate analysis of patient factors that led to rapid EWL identified initial BMI (49.3 vs. 46.6 kg/m2) and rapid EWL as increasing the likelihood of developing IH (p=0.026). A multivariate logistic model for IH identified only rapid EWL as a predictive factor. Locations of IH were the jejunojejunostomy (24), Pedersen's defect (23), adhesions (9), and colonic mesentery (1). There were five patients with combined JJ and Pederson's hernias. CONCLUSION Outcomes from missed IH can be catastrophic. In our large, single-center series, we have found that patients who undergo periods of rapid EWL are at nearly twice the risk for development of IH as the rest of the gastric bypass population.

negative: COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm? From January 2020, coronavirus disease (COVID-19) originated in China has spread around the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of myocarditis, cardiac arrest, and acute heart failure in COVID-19 patients suggests the existence of a relationship between SARS-CoV-2 infection and cardiac disease. The Notch signalling is a major regulator of cardiovascular function and it is also implicated in several biological processes mediating viral infections. In this report we discuss the possibility to target Notch signalling to prevent SARS-CoV-2 infection and interfere with the progression of COVID-19- associated heart and lungs disease.

negative: Are coinfections with COVID-19 and influenza low or underreported? An observational study examining current published literature including three new unpublished cases As the coronavirus disease-2019 (COVID-19) pandemic continues, one major point of uncertainty is the impact this novel pathogen will have during the upcoming 2020 to 2021 flu season. While the influenza virus is a known contributor to human morbidity and mortality, the question of how a coinfection between COVID-19 and influenza might manifest is of utmost concern. The aim of this study was to review the limited cases of COVID-19/influenza coinfection currently available in the literature, along with cases in the community of El Paso, TX, to determine whether any patterns of clinical presentation and morbidity emerged. An international review of the literature was conducted. Six published articles describing COVID-19/influenza coinfection were identified, with a total of 13 patients described therein. Three additional patients were identified from the El Paso, TX data. The most common presenting symptoms were fever and cough. The most common laboratory findings were elevated C-reactive protein and lymphocytopenia. Thirteen patients presented with viral pneumonia findings on CT, and nine had findings of ground-glass opacity. Finally, complications were reported in six patients, with most common complication being acute respiratory distress syndrome. The results of the review indicate that, due to the similarity in presentation between COVID-19 and influenza, further analysis will be required to understand the effects of coinfection on morbidity and mortality. However, the limited number of coinfection cases in the literature indicates that the implementation of COVID-19 control measures may continue to play a role in limiting the spread of these human respiratory pathogens.

negative: The prospect of pandemic influenza: Why should the optometrist be concerned about a public health problem? Abstract Background Optometrists are uniquely placed in the health care field because they provide both services as well as goods to patients. In the event of an influenza pandemic, optometrists may be challenged with a host of issues, including impediments to clinical patient care, manufacture and delivery of ophthalmic devices, and maintaining business continuity and infection control. Overview This report reviews pandemic influenza, the effect of a pandemic event on business survival, and response measures for the primary eye care provider. The ethical and legal issues surrounding control of a pandemic influenza and the prospect of telemedicine as a form of social distancing are also discussed. Conclusions Knowledge of the pharmacologic and nonpharmacologic measures to control a pandemic influenza will help prepare the eye care provider for addressing challenges to patient care and business continuity in the face of a highly contagious disease. Understanding the legal and ethical issues that arise during a pandemic event will help optometrists make informed choices as health care professionals and as citizens.

negative: Influenza Virus: The Biology of a Changing Virus Influenza viruses are members of the family Orthomyxoviridae and include influenza virus types A, B, and C. This introduction provides an overview of influenza virus classification, structure, and life cycle. We also include a brief review of the clinical manifestations of influenza and the molecular determinants for virulence. The genetic diversity of influenza A viruses and their capability to successfully infect an array of hosts, including avian and mammalian species, are highlighted in a discussion about host range and evolution. The importance of viral receptor-binding hemagglutinins and host sialic acid distribution in species-restricted binding of viruses is underscored. Finally, recent advances in our understanding of the seasonality and transmission of influenza viruses are described, and their importance for the control of the spread of these viruses is discussed.

negative: Investigating the sex differences in COVID-19: Another step forward, but many unanswered questions

negative: COVID-19 Is Distinct From SARS-CoV-2-Negative Community-Acquired Pneumonia Background: Corona virus disease (COVID-19) is an infectious respiratory disease that has spread rapidly across the world. Many studies have already evaluated the clinical features of COVID-19, but how it compares with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) is still unclear. Moreover, COVID-19 mortality is correlated with disease severity, but indicators for severity grading have not been specified. We aimed to analyze the clinical characteristics of COVID-19 in comparison with SN-CAP and find indicators for disease severity in COVID-19. Methods: Patients diagnosed with COVID-19 and SN-CAP were enrolled. Clinical, radiological, and laboratory data were analyzed. Results: The numbers of COVID-19 and SN-CAP patients enrolled were 304 and 138, respectively. The age of the patients was not significantly different between the groups. Compared with SN-CAP, COVID-19 patients had more symptoms of fever and dyspnea; and showed significant difference in blood count results. Computed tomography (CT) imaging of COVID-19 patients showed patchy ground-glass opacities that correlated with disease severity, whereas the CT imaging of SN-CAP patients showed patchy high-density shadows. COVID-19 patients were classified into moderate, severe, and critically severe groups. The severe and critically severe groups had elevated levels of white blood cells (WBC), neutrophils, platelets, C-reaction protein (CRP), lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), troponin-I, creatinine, and blood urea nitrogen (BUN). However, they had decreased levels of lymphocytes, lymphocyte ratio, and albumin. Compared with the younger patients, the older COVID-19 individuals had more chronic diseases and significantly elevated levels of WBC, neutrophil, and CRP levels. Conclusion: SN-CAP showed more inflammatory reaction than COVID-19. Old people with chronic diseases are more susceptible to COVID-19 and have a high likelihood of developing severe and critically severe infection. Levels of WBC, lymphocytes, neutrophils, CRP, NLR, PLR, troponin-I, creatinine, and BUN are important indicators for severity grading in COVID-19.

negative: COVID-19 randomised trial protocols: rapid publication without barriers

negative: Epidemiology of Viral Infections and Evaluation of the Potential Benefit of OM-85 BV on the Virologie Status of Children Attending Day-Care Centers Viral investigations were performed during 4 winter seasons (88/89, 89/90, 92/93, 93/94) in children attending day-care centers (DCCs) in the Rhone Département in eastern France. Over the total observation period of 4 winter seasons, 780 children were screened with a nasal swab for the presence of viruses. Of those, 230 (29.5%) had a positive viral culture. The viruses identified were respiratory syncytial virus (RSV), influenza A and B virus, parain-fluenza virus, coronavirus, rhinovirus, adenovirus and enterovirus. During that time, 83 epidemic events in 47 DCC were recorded. A particular virus was judged to be causally related to an epidemic if the identical virus was isolated in ≥ 3 children during the same outbreak of respiratory diseases. Thus, in 51 cases (61.4%) of all epidemics, the following viruses were responsible for an epidemic: RSV (n = 23), coronavirus (n = 10) (only during the season of 1993-1994), influenza A virus (n = 6), rhinovirus (n = 4), enterovirus (n = 4), adenovirus (n = 3) and parainfluenza virus (n = 1). Except for the somewhat surprising accumulation of coronavirus epidemics during the winter of 1993-1994, there were only minor seasonal variations from one year to another. As expected, RSV accounted for about one third of all respiratory tract infections in children attending DCCs and was therefore the most important single causative agent. These results are compared with data from children who did not attend a DCC and were cared for in a private practice. During the winter of 1989-1990, the viral epidemiological survey was performed at the same time and in parallel to a double-blind, placebo-controlled clinical study investigating the efficacy of OM-85 BV, an immunoactive bacterial extract. This study, enrolling 423 children attending DCCs demonstrated a protective effect of OM-85 BV in significantly reducing the risk of recurrent infections of the upper respiratory tract during the treatment period with the compound. 34% of all participating children (75 in the verum group, 70 in the placebo group) were enrolled in an additional virological study. In these patients, RSV was isolated 10 times in the placebo group, but only 5 times in the treated group (p < 0.05) and influenza A virus was present in 4 children in the placebo group, but only in 1 infant in the verum group giving a total of 14 positive virologie results in the placebo group versus 6 in the verum group (p < 0.05). Despite the small numbers of children investigated for their virologie status during respiratory infectious outbreaks, there was a statistically significant difference in the prevalence of virus carriers in favor of the children treated with OM-85 BV. These results corroborate the clinical findings.

negative: Climate effect on COVID-19 spread rate: an online surveillance tool Background: COVID-19 outbreak poses an unprecedented challenge for societies, healthcare organizations and economies. In the present analysis we coupled climate data with COVID-19 spread rates worldwide, and in a single country (USA). Methods: Data of confirmed COVID-19 cases was derived from the COVID-19 Global Cases by the CSSE at Johns Hopkins University up to March 19, 2020. We assessed disease spread by two measures: replication rate (RR), the slope of the logarithmic curve of confirmed cases, and the rate of spread (RoS), the slope of the linear regression of the logarithmic curve. Results: Based on predefined criteria, the mean COVID-19 RR was significantly lower in warm climate countries (0.12± 0.02) compared with cold countries (0.24± 0.01), (P<0.0001). Similarly, RoS was significantly lower in warm climate countries 0.12± 0.02 vs. 0.25± 0.01 than in cold climate countries (P<0.001). In all countries (independent of climate classification) both RR and RoS displayed a moderate negative correlation with temperature R= -0.69, 95% confidence interval [CI], -0.87 to -0.36; P<0.001 and R= -0.72, 95% confidence interval [CI], -0.87 to -0.36; P<0.001, respectively. We identified a similar moderate negative correlation with the dew point temperature. Additional climate variables did not display a significant correlation with neither RR nor RoS. Finally, in an ancillary analysis, COVID-19 intra-country model using an inter-state analysis of the USA did not identify yet correlation between climate parameters and RR or RoS as of March, 19, 2020. Conclusions: Our analysis suggests a plausible negative correlation between warmer climate and COVID-19 spread rate as defined by RR and RoS worldwide. This initial correlation should be interpreted cautiously and be further validated over time, the pandemic is at different stages in various countries as well as in regions within these countries. As such, some associations may be more affected by local transmission patterns rather than by climate. Importantly, we provide an online surveillance dashboard (https://covid19.net.technion.ac.il/) to further assess the association between climate parameters and outbreak dynamics worldwide as time goes by

negative: Clinical and epidemiological features of respiratory virus infections in preschool children over two consecutive influenza seasons in southern Brazil This study reports the results of a systematic screening for respiratory viruses in pediatric outpatients from an emergency department (ED) in southern Brazil during two consecutive influenza seasons. Children eligible for enrollment in this study were aged 24–59 months and presented with acute respiratory symptoms and fever. Naso‐ and oropharyngeal swabs were collected and multiplex reverse transcription PCR (RT‐PCR) was performed to identify the respiratory viruses involved. In total, 492 children were included in this study: 248 in 2010 and 244 in 2011. In 2010, 136 samples (55%) were found to be positive for at least one virus and the most frequently detected viruses were human rhinovirus (HRV) (18%), adenovirus (AdV) (13%), and human coronavirus (CoV) (5%). In 2011, 158 samples (65%) were found to be positive for at least one virus, and the most frequently detected were HRV (29%), AdV (12%), and enterovirus (9%). Further, the presence of asthma (OR, 3.17; 95% CI, 1.86–5.46) was independently associated with HRV infection, whereas fever was associated with AdV (OR, 3.86; 95% CI, 1.31–16.52) and influenza infections (OR, 3.74; 95% CI, 1.26–16.06). Ten patients (2%) were diagnosed with pneumonia, and six of these tested positive for viral infection (4 HRV, 1 RSV, and 1 AdV). Thus, this study identified the most common respiratory viruses found in preschool children in the study region and demonstrated their high frequency, highlighting the need for improved data collection, and case management in order to stimulate preventive measures against these infections. J. Med. Virol. 88:1325–1333, 2016. © 2016 Wiley Periodicals, Inc.

negative: Environmental Factors Affecting the Transmission of Respiratory Viruses Many viruses are capable of infecting the human respiratory tract to cause disease. These viruses display various transmission patterns among humans; however, they all share the ability to transmit from person to person, and their human transmissibility is influenced by the environment in which pathogen and host meet. This review aims to summarize recent and significant observations regarding the impact of environmental factors such as weather and climate, humidity, temperature, and airflow on the transmission of human respiratory viruses. Where possible, knowledge gaps that require further scientific study will be identified.

negative: Public views of the uk media and government reaction to the 2009 swine flu pandemic BACKGROUND: The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. METHODS: Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. RESULTS: These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. CONCLUSIONS: This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.

negative: Form follows function: the importance of endoplasmic reticulum shape. The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. These studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure.

negative: Impact of the 2009 Influenza (H1N1) Pandemic on the United States Military Health Care System Background: During public health emergencies, the Military Health System experiences challenges similar to those across the U.S. public and private health systems. This study explored how 1 such event, the 2009/2010 influenza (H1N1) pandemic, impacted health care utilization and associated costs in the Military Health System. Methods: Data from the Military Data Repository were used to examine diagnoses, claims data, and dates of services with respect to military or civilian care during 2004–2009/2010 influenza seasons. Comparison analysis was conducted through two-tailed t-tests and regression models. Results: There was a significant increase in inpatient and outpatient health care utilization during the 2009/2010 H1N1 pandemic year, most markedly for emergency department visits. The 2009/2010 H1N1 pandemic cost the Department of Defense $100 million compared to influenza-related health care costs incurred in previous influenza seasons. Highest health care utilization costs were found in children less than age 5. The greatest cost burden was attributed to immunizations for active duty personnel delivered at military facilities. Conclusion: Annual trend analysis of costs and health care utilization would be helpful to plan and resource emerging influenza pandemics and to identify subgroups at greatest risk for contracting influenza.

negative: Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

negative: The Prevalence of Human Bocavirus, Human Coronavirus-NL63, Human Metapneumovirus, Human Polyomavirus KI and WU in Respiratory Tract Infections in Kuwait OBJECTIVE: The aim of this study was to investigate the prevalence of human coronavirus (HCoV)-NL63, human metapneumovirus (hMPV), human bocavirus (Boca), human polyomavirus KI (KIV) and human polyomavirus WU (WUV) in respiratory tract infections (RTI) in Kuwait. MATERIALS AND METHODS: Respiratory samples from 735 hospitalized patients with RTI from September 2010 to April 2013 were evaluated for the presence of HCoV-NL63, hMPV, Boca, KIV and WUV using molecular assays, polymerase chain reaction (PCR) and reverse-transcription PCR. RESULTS: Of the 735 patients, 285 (38.8%) were diagnosed with viral RTI. The distribution of respiratory viruses was hMPV: 15 (5.3%), Boca: 14 (4.9%), WUV: 10 (3.5%) and KIV: 4 (1.4%). HCoV-NL63 was not detected in any of the samples. CONCLUSIONS: These newly discovered viruses were associated with the development of RTI in Kuwait. The rapid identification of these viral infections could aid in the control of nosocomial transmission, reduce the use of antibiotics and improve treatment and management strategies.

negative: Tracheal Infections Infectious processes of the trachea represent a distinct clinical entity with an evolving landscape owing to advances in airway management and vaccination practices. Untreated inflammatory processes of the trachea may present in the form of acute airway obstruction, potentially resulting in significant morbidity and even mortality. Therefore it is important to recognize the cardinal features of some of the common tracheal infectious processes to differentiate them from non-infectious pathology, as the latter is associated with a more indolent course. As with most other infectious processes of the airway, pathogens causing tracheal infection can be bacterial, viral or fungal in nature. Viral etiology represents the most common cause of laryngotracheal infection in a child. Bacterial infections of the trachea are responsible for more significant morbidity, including prolonged hospitalization, need for endotracheal intubation and even an occasional tracheostomy. The current chapter describes the clinical features and microbiology of tracheal infections at large, explores the utility of diagnostic tests, and provides an algorithm for management.

negative: COVID-19 on Social Media: Analyzing Misinformation in Twitter Conversations The ongoing Coronavirus Disease (COVID-19) pandemic highlights the interconnected-ness of our present-day globalized world. With social distancing policies in place, virtual communication has become an important source of (mis)information. As increasing number of people rely on social media platforms for news, identifying misinformation has emerged as a critical task in these unprecedented times. In addition to being malicious, the spread of such information poses a serious public health risk. To this end, we design a dashboard to track misinformation on popular social media news sharing platform - Twitter. The dashboard allows visibility into the social media discussions around Coronavirus and the quality of information shared on the platform, updated over time. We collect streaming data using the Twitter API from March 1, 2020 to date and identify false, misleading and clickbait contents from collected Tweets. We provide analysis of user accounts and misinformation spread across countries. In addition, we provide analysis of public sentiments on intervention policies such as"#socialdistancing"and"#workfromhome", and we track topics, and emerging hashtags and sentiments over countries. The dashboard maintains an evolving list of misinformation cascades, sentiments and emerging trends over time, accessible online at https://usc-melady.github.io/COVID-19-Tweet-Analysis. Keywords. COVID-19, Misinformation, Fake News, Social Media

negative: Respiratory tract virus infections in the elderly with pneumonia BACKGROUND: In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia. METHODS: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints. RESULTS: Median age of the patients was 83 years (range 76–90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 10(9)/L (P = .006) and a CRP value over 80 mg/l (P < .05). A virus was detected in 30% of pneumonia episodes and in 40% of non-pneumonia episodes, but this difference was not significant (P = 0.09). The presence of a respiratory virus was associated with fewer revisits to the hospital (P < .05), whereas a CRP value over 100 mg/l was associated with death during hospital stay (P < .05). Respiratory virus detections did not correlate to WBC or CRP values, signs and symptoms or prognosis of radiographically-verified pneumonia episodes. CONCLUSION: Among the elderly with respiratory symptoms, respiratory virus detection was not associated with an increased risk of pneumonia or with a more severe clinical course of the illness. CRP and WBC remain important indicators of pneumonia, and according to our findings, pneumonia should be treated as a bacterial disease regardless of the virus findings. Our data does not support routine virus diagnostics for the elderly patients with pneumonia outside the epidemic seasons. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12877-019-1125-z) contains supplementary material, which is available to authorized users.

negative: Pandemics: good hygiene is not enough The US government is doing well to communicate uncertainty over swine flu. It must also help the public to visualize what a bad pandemic might be like, says Peter M. Sandman.

negative: Influenza-associated pneumonia as reference to assess seriousness of coronavirus disease (COVID-19) Information on severity of coronavirus disease (COVID-19) (transmissibility, disease seriousness, impact) is crucial for preparation of healthcare sectors. We present a simple approach to assess disease seriousness, creating a reference cohort of pneumonia patients from sentinel hospitals. First comparisons exposed a higher rate of COVID-19 patients requiring ventilation. There were more case fatalities among COVID-19 patients without comorbidities than in the reference cohort. Hospitals should prepare for high utilisation of ventilation and intensive care resources.

negative: Spread and control of COVID-19 in China and their associations with population movement, public health emergency measures, and medical resources ABSTRACT BACKGROUND The COVID-19 epidemic, first emerged in Wuhan during December 2019, has spread globally. While the mass population movement for Chinese New Year has significantly influenced spreading the disease, little direct evidence exists about the relevance to epidemic and its control of population movement from Wuhan, local emergency response, and medical resources in China. METHODS Spearman's correlation analysis was performed between official data of confirmed COVID-19 cases from Jan 20th to Feb 19th, 2020 and real-time travel data and health resources data. RESULTS There were 74,675 confirmed COVID-19 cases in China by Feb 19th, 2020. The overall fatality rate was 2.84%, much higher in Hubei than in other regions (3.27% vs 0.73%). The index of population inflow from Hubei was positively correlated with total (Provincial r=0.9159, p<0.001; City r=0.6311, p<0.001) and primary cases (Provincial r=0.8702, p<0.001; City r=0.6358, p<0.001). The local health emergency measures (eg, city lockdown and traffic control) were associated with reduced infections nationwide. Moreover, the number of public health employees per capita was inversely correlated with total cases (r=-0.6295, p<0.001) and infection rates (r=-0.4912, p<0.01). Similarly, cities with less medical resources had higher fatality (r=-0.4791, p<0.01) and lower cure rates (r=0.5286, p<0.01) among the confirmed cases. CONCLUSIONS The spread of the COVID-19 in China in its early phase was attributed primarily to population movement from Hubei, and effective governmental health emergency measures and adequate medical resources played important roles in subsequent control of epidemic and improved prognosis of affected individuals.

negative: STEM: An Open Source Tool for Disease Modeling The Spatiotemporal Epidemiologic Modeler (STEM) is an open source software project supported by the Eclipse Foundation and used by a global community of researchers and public health officials working to track and, when possible, control outbreaks of infectious disease in human and animal populations. STEM is not a model or a tool designed for a specific disease; it is a flexible, modular framework supporting exchange and integration of community models, reusable plug-in components, and denominator data, available to researchers worldwide at www.eclipse.org/stem. A review of multiple projects illustrates its capabilities. STEM has been used to study variations in transmission of seasonal influenza in Israel by strains; evaluate social distancing measures taken to curb the H1N1 epidemic in Mexico City; study measles outbreaks in part of London and inform local policy on immunization; and gain insights into H7N9 avian influenza transmission in China. A multistrain dengue fever model explored the roles of the mosquito vector, cross-strain immunity, and antibody response in the frequency of dengue outbreaks. STEM has also been used to study the impact of variations in climate on malaria incidence. During the Ebola epidemic, a weekly conference call supported the global modeling community; subsequent work modeled the impact of behavioral change and tested disease reintroduction via animal reservoirs. Work in Germany tracked salmonella in pork from farm to fork; and a recent doctoral dissertation used the air travel feature to compare the potential threats posed by weaponizing infectious diseases. Current projects include work in Great Britain to evaluate control strategies for parasitic disease in sheep, and in Germany and Hungary, to validate the model and inform policy decisions for African swine fever. STEM Version 4.0.0, released in early 2019, includes tools used in these projects and updates technical aspects of the framework to ease its use and re-use.

negative: Quantitative Relationship between Population Mobility and COVID-19 Growth Rate based on 14 Countries This study develops a framework for quantification of the impact of changes in population mobility due to social distancing on the COVID-19 infection growth rate. Using the Susceptible-Infected-Recovered (SIR) epidemiological model we establish that under some mild assumptions the growth rate of COVID-19 deaths is a time-delayed approximation of the growth rate of COVID-19 infections. We then hypothesize that the growth rate of COVID-19 infections is a function of population mobility, which leads to a statistical model that predicts the growth rate of COVID-19 deaths as a delayed function of population mobility. The parameters of the statistical model directly reveal the growth rate of infections, the mobility-dependent transmission rate, the mobility-independent recovery rate, and the critical mobility, below which COVID-19 growth rate becomes negative. We fitted the proposed statistical model on publicly available data from 14 countries where daily death counts exceeded 100 for more than 3 days as of May 6th, 2020. The publicly available Google Mobility Index (GMI) was used as a measure of population mobility at the country level. Our results show that the growth rate of COVID-19 deaths can be accurately estimated 20 days ahead as a quadratic function of the transit category of GMI (adjusted R-squared = 0.784). The estimated 95% confidence interval for the critical mobility is in the range between 36.1% and 47.6% of the pre-COVID-19 mobility. This result indicates that a significant reduction in population mobility is needed to reverse the growth of COVID-19 epidemic. Moreover, the quantitative relationship established herein suggests that a readily available, population-level metric such as GMI can be a useful indicator of the course of COVID-19 epidemic.

negative: Prevalence of facemask use among general public when visiting wet market during Covid-19 pandemic: An observational study. Background In late December 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV) was epidemiologically linked to seafood and wet animal wholesale market in Wuhan, Hubei, China. This has instigated stigma among the general population as the wet market is viewed as a high-risk location for getting infected with coronavirus. Objective This study investigated the prevalence of facemask use among general population visiting the wet market. This study also investigated the demographic factors contributing to unacceptable facemask practice. Setting This prospective observational study was done among visitor to a district wet market selling range of live or freshly slaughtered animals during COVID-19 pandemic outbreak. Methods Individuals entering through dedicated entry point were observed for the type, category and practice of wearing personal protective equipment. Inclusion criteria for this study were any individuals entering the wet market. Subjects were categorized into two groups of acceptable and unacceptable facemask practice. The Pearson chi-square was used to test for differences in investigated variables in the univariate setting and Binary Logistic regression model was used in the multivariate setting. Main outcome measure Prevalence, acceptance practice and odds ratio of unacceptance of facemask use. Results Among 1697 individuals included in the final analysis, 1687 (99.7%) was observed wearing facemask with 1338 (78.8%) using medical-grade facemask. Among them, 1615 (95.7%) individuals facemask practice was acceptable while the reaming 72 (4.3%) individuals were observed with unacceptable facemask practice. Individuals using medical-grade facemask and high-risk age group are 6.4 times (OR=6.40; 95% CI, 2.00-20.43; p=.002) and 2.06 times practice (OR=2.06; 95% CI, 1.08-3.94; p=.028). More likely to practice unacceptable facemask use respectively. Conclusion High saturation of facemask among the general population is an adequate indicator of public hygiene measures strategy which can help to mitigate the COVID-19 epidemic impact. Alarmingly, the unacceptable facemask practice among high-risk population raises the need for a targeted approach by healthcare authorities to ensure satisfactory facemask use.

negative: Diagnosis and management of vertebrobasilar insufficiency. OPINION STATEMENT Understanding the anatomical pathways and clinical presentations for VBI are of the utmost importance due to the potential mimics that may occur. After identification of the entity, imaging must be performed to identify the etiology. Distinguishing external compression of the vertebral artery from intrinsic vascular disease due to atherosclerosis or dissection is critical to aid the clinician in the therapeutic decision tree. Patients with an external compression due to an osteophyte may benefit from definitive surgical decompression and excision of the bony structure. Patients with extracranial disease of the vertebral artery who have failed maximal medical therapy may benefit from angioplasty and stenting which appears to carry a low morbidity. Extracranial vertebral artery dissections can be treated with medical therapy using anti-platelet agents or on occasion anti-coagulation. Rarely, endovascular options are required if a patient is having hemodynamic stroke or TIAs due to flow failure. In such circumstances, stenting and angioplasty may be considered. Intracranial atherosclerosis is best managed with maximal medical therapy due to the high rate of complications attributable to stenting and angioplasty.

negative: Viral Aetiology in Adults with Acute Upper Respiratory Tract Infection in Jinan, Northern China Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n = 596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14–25-year-old group than in the 26–65-year-old group. Codetection rates were higher (7.52%) in the 14–25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China.

negative: Middle East Respiratory Syndrome Coronavirus Quasispecies That Include Homologues of Human Isolates Revealed through Whole-Genome Analysis and Virus Cultured from Dromedary Camels in Saudi Arabia Complete Middle East respiratory syndrome coronavirus (MERS-CoV) genome sequences were obtained from nasal swabs of dromedary camels sampled in the Kingdom of Saudi Arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. Consensus dromedary MERS-CoV genome sequences were the same with either template source and identical to published human MERS-CoV sequences. However, in contrast to individual human cases, where only clonal genomic sequences are reported, detailed population analyses revealed the presence of more than one genomic variant in individual dromedaries. If humans are truly infected only with clonal virus populations, we must entertain a model for interspecies transmission of MERS-CoV wherein only specific genotypes are capable of passing bottleneck selection.

negative: High Level Antibody Response to Pandemic Influenza H1N1/09 Virus Is Associated With Interferon-Induced Transmembrane Protein-3 rs12252-CC in Young Adults Background: The C allele of the interferon-induced transmembrane protein-3 (IFITM3) SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection. However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%), severe influenza infection is rare. The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections. Cohort and Method: A total 99 young healthy volunteers (18–20 years) were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2), A/California/7/2009 (pdm09H1N1) and B/Jeep/3073/2013-like virus (Flu-B)]. Plasma and gDNA was isolated from each volunteer before, and 14, 28, 180, 360, and 540 days after vaccination. Additionally, 68 elderlies (>65 years) were also recruited as a control group to compare the levels of antibodies at baseline between the young adults and the elderly. For each sample IFITM3 rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point. Results: We found a significantly higher level of pre-existing antibodies to pandemic influenza H1N1/09 virus (pdm09H1N1) but not to H3N2 or FluB in CC donors in comparison with CT/TT donors prior to vaccination. No impact of IFITM3 genotype in boosting influenza specific antibodies in young adults within 1 year after receiving seasonal influenza vaccination was observed. In addition, there was no difference in pdm09H1N1 specific antibody levels observed in the elderly cohort between volunteers carrying different IFITM3 genotypes. Higher levels of antibodies to pdmH1N1 were observed in elderly CC carriers when compared to the young CC carriers, but this trend was not replicated in TT carriers. Conclusion: IFITM3-rs12252 CC carriers exhibit a high level of pre-existing immunity to pdm09H1N1 compared to TT carriers in the young cohort. This suggests that compensatory mechanisms exist which might contribute to viral control in patients carrying the rs12252-CC genotype who do not become sick after flu infection. However, such a potential compensatory effect appears to be lost overtime, as evidenced in the elderly cohort. If this compensatory mechanism is lost, it may make the CC carrying elderly more susceptible to severe influenza infection.

negative: Avian influenza viruses: a severe threat of a pandemic in children? Influenza virus is a leading cause of human respiratory illnesses, causing significant annual morbidity and mortality. The greatest severity of illness due to seasonal influenza occurs in infants less than 6 months of age and the elderly. In recent years, avian influenza virus infections with high mortality have occurred in humans. Many of these avian influenza virus infections have occurred in children, and unlike seasonal influenza, the most severe disease and highest death rates have occurred in children and young adults. Treatment and prevention options for avian influenza viruses are limited at present, although much research effort is directed toward these areas. Avian-derived influenza viruses are potential causes of pandemic influenza that could have a dramatic impact on children worldwide.

negative: The Heart in the Time of the ‘Coronavirus’

negative: Health Information–Seeking Patterns of the General Public and Indications for Disease Surveillance: Register-Based Study Using Lyme Disease BACKGROUND: People using the Internet to find information on health issues, such as specific diseases, usually start their search from a general search engine, for example, Google. Internet searches such as these may yield results and data of questionable quality and reliability. Health Library is a free-of-charge medical portal on the Internet providing medical information for the general public. Physician’s Databases, an Internet evidence-based medicine source, provides medical information for health care professionals (HCPs) to support their clinical practice. Both databases are available throughout Finland, but the latter is used only by health professionals and pharmacies. Little is known about how the general public seeks medical information from medical sources on the Internet, how this behavior differs from HCPs’ queries, and what causes possible differences in behavior. OBJECTIVE: The aim of our study was to evaluate how the general public’s and HCPs’ information-seeking trends from Internet medical databases differ seasonally and temporally. In addition, we aimed to evaluate whether the general public’s information-seeking trends could be utilized for disease surveillance and whether media coverage could affect these seeking trends. METHODS: Lyme disease, serving as a well-defined disease model with distinct seasonal variation, was chosen as a case study. Two Internet medical databases, Health Library and Physician’s Databases, were used. We compared the general public’s article openings on Lyme disease from Health Library to HCPs’ article openings on Lyme disease from Physician’s Databases seasonally across Finland from 2011 to 2015. Additionally, media publications related to Lyme disease were searched from the largest and most popular media websites in Finland. RESULTS: Both databases, Health Library and Physician’s Databases, show visually similar patterns in temporal variations of article openings on Lyme disease in Finland from 2011 to 2015. However, Health Library openings show not only an increasing trend over time but also greater fluctuations, especially during peak opening seasons. Outside these seasons, publications in the media coincide with Health Library article openings only occasionally. CONCLUSIONS: Lyme disease–related information-seeking behaviors between the general public and HCPs from Internet medical portals share similar temporal variations, which is consistent with the trend seen in epidemiological data. Therefore, the general public’s article openings could be used as a supplementary source of information for disease surveillance. The fluctuations in article openings appeared stronger among the general public, thus, suggesting that different factors such as media coverage, affect the information-seeking behaviors of the public versus professionals. However, media coverage may also have an influence on HCPs. Not every publication was associated with an increase in openings, but the higher the media coverage by some publications, the higher the general public’s access to Health Library.

negative: A study of non-prescription usage of antibiotics in the upper respiratory tract infections in the urban population

negative: MERS coronavirus: diagnostics, epidemiology and transmission The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users.

negative: Real Time Investigation of a large Nosocomial Influenza A Outbreak Informed by Genomic Epidemiology Background: Nosocomial respiratory virus outbreaks represent serious public health challenges. Rapid and precise identification of cases and tracing of transmission chains is critical to end outbreaks and to inform prevention measures. Methods: We combined conventional surveillance with Influenza A virus (IAV) genome sequencing to identify and contain a large IAV outbreak in a metropolitan healthcare system. A total of 381 individuals, including 91 inpatients and 290 health care workers (HCWs), were included in the investigation. Results: During a 12-day period in early 2019, infection preventionists identified 89 HCWs and 18 inpatients as cases of influenza-like illness (ILI), using an amended definition, without the requirement for fever. Sequencing of IAV genomes from available nasopharyngeal (NP) specimens identified 66 individuals infected with a nearly identical strain of influenza A H1N1 (43 HCWs, 17 inpatients, and 6 with unspecified affiliation). All HCWs infected with the outbreak strain had received the seasonal influenza virus vaccination. Characterization of five representative outbreak viral isolates did not show antigenic drift. In conjunction with IAV genome sequencing, mining of electronic records pinpointed the origin of the outbreak as a single patient and a few interactions in the emergency department that occurred one day prior to the index ILI cluster. Conclusions: We used precision surveillance to identify and control a large nosocomial IAV outbreak, mapping the source of the outbreak to a single patient rather than HCWs as initially assumed based on conventional epidemiology. These findings have important ramifications for more effective prevention strategies to curb nosocomial respiratory virus outbreaks.

negative: Information Mining for COVID-19 Research From a Large Volume of Scientific Literature The year 2020 has seen an unprecedented COVID-19 pandemic due to the outbreak of a novel strain of coronavirus in 180 countries. In a desperate effort to discover new drugs and vaccines for COVID-19, many scientists are working around the clock. Their valuable time and effort may benefit from computer-based mining of a large volume of health science literature that is a treasure trove of information. In this paper, we have developed a graph-based model using abstracts of 10,683 scientific articles to find key information on three topics: transmission, drug types, and genome research related to coronavirus. A subgraph is built for each of the three topics to extract more topic-focused information. Within each subgraph, we use a betweenness centrality measurement to rank order the importance of keywords related to drugs, diseases, pathogens, hosts of pathogens, and biomolecules. The results reveal intriguing information about antiviral drugs (Chloroquine, Amantadine, Dexamethasone), pathogen-hosts (pigs, bats, macaque, cynomolgus), viral pathogens (zika, dengue, malaria, and several viruses in the coronaviridae virus family), and proteins and therapeutic mechanisms (oligonucleotide, interferon, glycoprotein) in connection with the core topic of coronavirus. The categorical summary of these keywords and topics may be a useful reference to expedite and recommend new and alternative directions for COVID-19 research.

negative: Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.

negative: Clinical characteristics and outcomes during a severe influenza season in China during 2017–2018 BACKGROUND: A severe seasonal influenza epidemic was observed during 2017–2018 in China, prompting questions on clinical characteristics and outcomes of severe cases with influenza. METHODS: We retrospectively collected clinical data and outcomes of laboratory-confirmed hospitalized patients (severe to critical) during Jan-2011 to Feb-2018 from five hospitals, followed by a systematic analysis of cases from 2017 to 2018 (n = 289) and all previous epidemics during 2011–2017 (n = 169). RESULTS: In-hospital fatality was over 5-folds higher during the 2017–2018 (p < 0.01) in which 19 patients died (6.6%), whereas only 2 mortalities (1.2%) were observed during 2011–2017. Of the 289 hospitalized in 2017–2018, 153 were confirmed with influenza B virus, 110 with A/H1N1pdm09, and 26 A/H3N2, whereas A/H1N1pdm09 was the predominant cause of hospitalization in previous seasons combined (45%). Fatal cases in 2017–2018 were exclusively associated with either influenza B or A/H1N1pdm09. Our results show that a significant lower proportion of patients aged 14 or greater were treated with oseltamivir, during the 2017–2018 epidemic, and exhibited higher levels of clinical severity. CONCLUSIONS: In-hospital fatality rate might be significantly higher in the 2017–2018 season in China. A sufficient supply of oseltamivir and antiviral therapy within 48 h from onset could reduce fatality rates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-4181-2) contains supplementary material, which is available to authorized users.

negative: The difference in the incubation period of 2019 novel coronavirus (SARS-CoV-2) infection between travelers to Hubei and non-travelers: The need of a longer quarantine period Data collected from the individual cases reported by the media were used to estimate the distribution of the incubation period of travelers to Hubei and non-travelers. Upon the finding of longer and more volatile incubation period in travelers, the duration of quarantine should be extended to three weeks.

negative: Assessment of ambulance dispatch data for surveillance of influenza-like illness in Melbourne, Australia Summary Objectives Ambulance dispatch data are collated electronically in many jurisdictions and have a wide reach into the community. They may therefore be useful for syndromic surveillance and early recognition of emerging infectious diseases. This study assessed whether ambulance dispatch data are suitable for influenza surveillance. Study design Comparison of a time series of ambulance dispatch data from Melbourne, Australia for the years 1997–2005 with locum service and general practice (GP) sentinel surveillance data for influenza-like illness (ILI). Methods All data were aggregated into 1-week periods, corresponding to the data collection period used in the GP sentinel surveillance system, which was used as the reference system. Rates of ambulance dispatches classified to respiratory or breathing problems per 1000 total dispatches were compared with rates of callouts for flu or influenza per 1000 locum calls, and rates of ILI per 1000 patients from the sentinel GPs. Signals from the ambulance data were generated using the log likelihood ratio CUSUM, a method of continuous monitoring suitable for surveillance. Results The ambulance dispatch data displayed seasonal trends that were similar to those observed in locum service surveillance and GP sentinel systems, and identified the years with higher-than-expected seasonal ILI activity (1998 and 2003) and the epidemic year (1997). However, there was a high baseline rate of ambulance calls classified to respiratory or breathing problems (90–100 per 1000 calls) in months where there was minimal influenza activity. Conclusion Ambulance dispatch data have potential for syndromic surveillance, but because of the high background noise are not definitive and would need to be calibrated to suit particular local circumstances.

negative: Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine monoclonal antibodies (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection in vitro (Lip KM et al, J Virol. 2006 Jan; 80(2): 941–50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S protein at a novel epitope within the S2 subunit at amino acids 1111–1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.

negative: Non-COVID-19 Deaths After Social Distancing in Norway Lay persons and policy makers have speculated on how the imposition of social distancing to reduce SARS CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has affected non-COVID-19 (coronavirus disease of 2019) deaths. No rigorous estimation of the effect appears in the scholarly literature. We use time-series methods to compare non-COVID-19 deaths observed in Norway before and during the epidemic to those expected from non-COVID-19 deaths in Sweden as well as from the history of Norwegian mortality trends. We find that in the first 8 weeks after the divergence between Swedish and Norwegian policies (the only period for which dependable data can be had) approximately 650 fewer Norwegians died than expected.

negative: Rapid Antigen Tests for Diagnosis of Pandemic (Swine) Influenza A/H1N1 We found that the sensitivities of 3 rapid influenza antigen tests for pandemic influenza A/H1N1 virus were low to moderate: BD Directigen EZ Flu A+B test (Becton Dickinson), 46.7%; BinaxNOW Influenza A&B (Inverness Medical), 38.3%; and QuickVue Influenza A+B Test (Quidel), 53.3%. A patient with influenza-like illness who has a negative rapid antigen test result should undergo further testing using reverse-transcription polymerase chain reaction.

negative: COVID‐19: Important Therapy Considerations and Approaches in this Hour of Need We are living in unprecedented times. While we had near pandemic events in the recent past with SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome), we have never experienced anything like coronavirus (COVID-19), also known as SARS-CoV-2 infection, since the Spanish flu. In contrast to the Spanish flu where medical care was limited, we are equipped to combat COVID-19 but there is considerable work ahead with many uncertainties. At this critical time, we must come together as one united country and world to stop the spread and provide the best care possible for individuals who contract the virus and develop infection. A number of novel and repurposed therapies agents with activity against SARS-CoV-2 have been identified and most institutions have developed clinical pathways to operationalize their use in appropriate COVID-19 patients.1-3 However, optimal drug therapy decisions for those with moderate to severe COVID-19 infections are extremely challenging at this time as evidence is limited.

negative: Public perceptions of COVID-19 in Australia: perceived risk, knowledge, health-protective behaviours, and vaccine intentions Widespread and sustained engagement with health-protective behaviours (i.e., hygiene and distancing) is critical to successfully managing the COVID-19 pandemic. Evidence from previous emerging infectious disease outbreaks points to the role of perceived risk, worry, media coverage, and knowledge in shaping engagement with health-protective behaviours as well as vaccination intentions. The current study examined these factors in 2,174 Australian residents. An online survey was completed between 2-9 March 2020, at an early stage of the COVID-19 outbreak in Australia. Results revealed that two thirds of respondents were at least moderately worried about a widespread COVID-19 outbreak in Australia (which subsequently occurred). Worry about the outbreak and closely following media coverage were consistent predictors of health-protective behaviours (both over the previous month, and intended behaviours in the case of a widespread outbreak) as well as vaccination intentions. Health-behaviour engagement over the previous month was lower in some demographic groups, including males and younger individuals (18-29 age group). These was a substantial mismatch between respondents' expected symptoms of infection and emerging evidence that a meaningful proportion of people who contract the novel coronavirus will experience asymptomatic infection (i.e., they will not experience symptoms associated with COVID-19). Only 0.3% of those in the current study believed that they personally would not experience any symptoms if they were infected. Uncertainty and misconceptions about COVID-19 were common, including one third of respondents who reported being unsure whether people are likely have natural or existing immunity. There was also uncertainty around whether specific home remedies (e.g., vitamins, saline rinses) would offer protection, whether the virus could spread via the airborne route, and whether the virus was human made and deliberately released. Such misconceptions are likely to cause concern for members of the public. These results point to areas of uncertainty that could be usefully targeted by public education campaigns, as well as psychological and demographic factors associated with engagement with health-protective behaviours. These findings offer potential pathways for interventions to encourage health-protective behaviours to reduce the spread of COVID-19.

negative: Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.

negative: Access to Care for Dementia patients suffering from COVID-19

negative: Metagenomic Analysis of the Ferret Fecal Viral Flora Ferrets are widely used as a small animal model for a number of viral infections, including influenza A virus and SARS coronavirus. To further analyze the microbiological status of ferrets, their fecal viral flora was studied using a metagenomics approach. Novel viruses from the families Picorna-, Papilloma-, and Anelloviridae as well as known viruses from the families Astro-, Corona-, Parvo-, and Hepeviridae were identified in different ferret cohorts. Ferret kobu- and hepatitis E virus were mainly present in human household ferrets, whereas coronaviruses were found both in household as well as farm ferrets. Our studies illuminate the viral diversity found in ferrets and provide tools to prescreen for newly identified viruses that potentially could influence disease outcome of experimental virus infections in ferrets.

negative: Infectious Disease Epidemiology Most textbooks dealing with the epidemiology of infectious diseases address the epidemiological features (also named biology) of specific infectious diseases. In this chapter, the focus is placed on the concepts and methods more specific to the general epidemiological study of infectious diseases. At a later stage, implementation of these methods must be adapted to the specific infectious disease under consideration. Then, detailed knowledge of the disease biology is of capital importance.

negative: Controlling avian flu at the source Global agricultural authorities should harmonize with the public-health sector to ensure the exchange of flu virus samples, and establish a single international standard for vaccines, say Robert Webster and Diane Hulse.

negative: Early data on the performance of a combined SARS-CoV-2 spike-nucleocapsid antibody lateral flow device compared to a nucleocapsid-only device Background There is a critical need for reliable antibody detection methods in order to study and evaluate the public health and clinical response to the ongoing COVID-19 pandemic. Lateral flow immunoassay (LFIA) devices offer the prospect of rapid point-of-care testing (POCT), but the performance of these devices must be evaluated for robustness before they can be adopted for routine clinical and public health use. Methods Plasma and serum specimens from SARS-CoV-2 RNA-positive (n = 131) and RNA-negative (n = 16) patients were taken from various time points with respect to the onset of symptoms. All 147 anonymised specimens were tested for IgM and IgG using the Hangzhou AllTest 2019-nCoV IgG/IgM Rapid Test Cassette and the Abbexa COVID-19 IgG/IgM Rapid Test Kit. Results IgM sensitivity ranged from 13% to 68%, depending on the date of symptom onset and the device. Regarding IgG, the Abbexa device outperformed the Hangzhou device at all cumulative timeline brackets, with sensitivity of 97·87% (Abbexa) versus 68·09% (Hangzhou) for samples beyond 21 days from symptom onset. Day 21 was therefore chosen as the cut-off for ascertaining test performance characteristics, beyond which the specificity was 100% for both devices and negative predictive value was 0·94 (Abbexa) versus 0·50 (Hangzhou). Discussion Based on this limited dataset, the performance characteristics of the Abbexa LFIA device were substantially better than those of the Hangzhou device. Applying a 21-day cut-off for the Abbexa device meets the minimum (98%) sensitivity and specificity thresholds set by the UK Medicine & Healthcare products Regulatory Agency. The Abbexa device captures antibodies against both SARS-CoV-2 spike and nucleocapsid proteins, as opposed to Hangzhou that targets only the nucleocapsid protein. We therefore propose that spike glycoprotein antibodies be considered as part of the standard diagnostic approach towards SARS-CoV-2 antibody profiling to improve clinical sensitivity and potentially specificity, pending follow-up studies to confirm this approach.

negative: Efficacy and safety of Jinhua Qinggan granules for coronavirus disease 2019 (COVID-19): A protocol of a systematic review and meta-analysis BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome (SARS)-COV2 and represents the causative agent of a potentially fatal disease. Jinhua Qinggan granules has definite effect in treating COVID-19 patients, but it has not been systematically evaluated for efficacy and safety. METHODS: Retrieved the database, including the China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, and EMBASE. Evaluate methodological quality and judge risk of bias through the Cochrane manual. RevMan 5.3 and STATA 16.0 software were used to perform the meta-analysis. RESULTS: This study will provide high-quality evidence of Jinhua Qinggan granules for COVID-19. CONCLUSION: The conclusion of this study will provide evidence to determine whether Jinhua Qinggan granules is an effective treatment for COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020182373.

negative: The Global Threats from Naturally Occurring Infectious Diseases Biological risk relates to a broad spectrum of possible scenarios, that can be classified in three categories: natural occurring, unintended and deliberate. The prevention and management of such events require dedicated measures at national and international level, in terms of biosafety and biosecurity: an optimized intervention can minimize the probability of occurrence, but also adverse short-term (i.e.: number of casualties, population reaction…) and long-term (i.e.: chronic illnesses, ecological changes, trades drop…) consequences. Natural scenarios include common, emerging/re-emerging and chronic infectious diseases: they are caused by biological agents, which can be normally present in the communities, as acute or chronic pathologies, or suddenly appear, causing new or uncommon syndromes. In particular, a lot of environmental and human factors can influence emerging and re-emerging diseases: for example, urbanization and people mobility facilitate microorganisms spread, while climate changes are likely to induce a relocation of pathogens vectors. Unintended events are usually due to research and diagnostic activities: laboratories are the places where biological agents are handled and a lack in Biosafety measures or negligence can result in accidental release; the so called Laboratory Acquired Infections represent the main consequence, since they cause pathologies in the laboratory workers, but could be also transmitted in the population. Deliberate use of biological agents is strictly related to terroristic activities: microorganisms are very suitable for this purpose, since they are hidden and can easily spread. The present chapter summarizes the main characteristics of biological agents related events, taking in account their origin and the principal consequences on the community.

negative: Human Coronavirus EMC Is Not the Same as Severe Acute Respiratory Syndrome Coronavirus A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in mBio, Müller et al. described several important differences between the two viruses [M. A. Müller et al., mBio 3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor-2 (hACE2). These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions.

negative: Use of lung ultrasound to differentiate COVID-19 pneumonia from community-acquired pneumonia To investigate the feasibility of lung ultrasound in evaluating coronavirus disease 2019 (COVID-19) and distinguish the sonographic features between COVID-19 and community-acquired pneumonia (CAP), a total of 12 COVID-19 patients and 20 CAP patients were selected and underwent the lung ultrasound. Modified Buda scoring system for interstitial lung disease (ILD) was used to evaluate the severity and treatment effect of COVID-19 on ultrasonography. The differences between modified lung ultrasound (MLUS) score and high-resolution computed tomography (HRCT) Warrick score were analyzed to evaluate their correlation. COVID-19 showed the following sonographic features: thickening (12/12), blurred (9/12), discontinuous (6/12) pleural line; rocket sign (4/12), partially diffused B-line (12/12), completely diffused B-line (10/12), waterfall sign (4/12); C-line sign (5/12); pleural effusion (1/12), and pulmonary balloon (Am line, 1/12). The last two features were rarely seen. Differences of ultrasonic features, including lesion range, lung signs and pneumonia-related complications, between COVID-19 and CAP were statistically significant (P<0.05 or 0.001). MLUS scores (P=0.006) and HRCT Warrick scores (P=0.015) increased as the severity of COVID-19 increased. The differences between moderate [29.00(25.75-37.50)] and severe [43.00(38.75-47.25)] (P=0.022) or between moderate and critical [47.50(44.25-50.00)] (P=0.002) type COVID-19 were statistically significant, compared with those between severe and critical types. Correlation between MLUS scores and HRCT Warrick scores was positive (r=0.54, P=0.048). MLUS scores (Z=2.61, P=0.009) and HRCT Warrick scores (Z=2.63, P=0.009) of five severe or critical COVID-19 patients significantly decreased as their conditions improved after treatment. The differences of sonographic features between COVID-19 and CAP patients were notable. The MLUS scoring system could be used to evaluate the severity and treatment effect of COVID-19.

negative: Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends BACKGROUND: Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections. METHODS AND FINDINGS: Influenza activity data from 2003–04 through 2007–08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearson's correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearson's correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003–04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90). CONCLUSIONS: This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003–04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.

negative: Etiology and genetic evolution of canine coronavirus circulating in five provinces of China, during 2018–2019 Abstract As the outbreaks of COVID-19 in worldwide, coronavirus has once again caught the attention of people. Canine coronavirus is widespread among dog population, and sometimes causes even fatal cases. Here, to characterize the prevalence and evolution of current circulating canine coronavirus (CCoV) strains in China, we collected 213 fecal samples from diarrheic pet dogs between 2018 and 2019. Of the 213 samples, we found 51 (23.94%) were positive for CCoV. Co-infection with canine parvovirus (CPV), canine astrovirus (CaAstV), canine kobuvirus (CaKV), Torque teno canis virus (TTCaV) were ubiquitous existed. Mixed infection of different CCoV subtypes exists extensively. Considering the limited sequences data in recent years, we sequenced 7 nearly complete genomes and 10 complete spike gene. Phylogenetic analysis of spike gene revealed a new subtype CCoV-II Variant and CCoV-IIa was the most prevalent subtype currently circulating. Moreover, we identified strain B906_ZJ_2019 shared 93.24% nucleotide identifies with previous strain A76, and both of them clustered with CCoV-II Variant, which were not well clustered with the known subtypes. Recombination analysis of B906_ZJ_2019 indicated that strain B906_ZJ_2019 may a recombinant variant between CCoV–I and CCoV-II, which is consistent with strain A76. Furthermore, amino acid variations widely existed among current CCoV-IIa strains circulating in China and the classic CCoV-IIa strains, in spite of the unknown functions. In a word, we report a useful information as to the etiology and evolution of canine coronavirus in China based on the available sequences, which is urgent for the devise of future effective disease prevention and control strategies.

negative: Estimating Influenza Vaccine Effectiveness With the Test-Negative Design Using Alternative Control Groups: A Systematic Review and Meta-Analysis One important assumption in case-control studies is that control selection should be independent of exposure. Nevertheless, it has been hypothesized that virus interference might lead to a correlation between receipt of influenza vaccination and increased risk of infection with other respiratory viruses. We investigated whether such a phenomenon might affect a study design commonly used to estimate influenza vaccine effectiveness (VE). We searched publications in MEDLINE, PubMed, and Web of Science. We identified 12 studies using the test-negative design (2011–2017) that reported VE estimates separately derived by 3 alternative control groups: 1) all patients testing negative for influenza (FLU), VE(FLU−); 2) patients who tested positive for other/another respiratory virus (ORV), VE(ORV+); and 3) patients who tested negative for all viruses in the panel (PAN), VE(PAN−). These included VE estimates from 7 countries for all age groups from 2003/2004 to 2013/2014. We observed no difference in vaccination coverage between the ORV-positive and PAN-negative control groups. A total of 63 VE(FLU−) estimates, 62 VE(ORV+) estimates, and 33 VE(PAN−) estimates were extracted. Pooled estimates of the difference in VE (ΔVE) were very similar between groups. In meta-regression, no association was found between the selection of control group and VE estimates. In conclusion, we did not find any differences in VE estimates based on the choice of control group.

negative: Advances in Visualization Tools for Phylogenomic and Phylodynamic Studies of Viral Diseases Genomic and epidemiological monitoring have become an integral part of our response to emerging and ongoing epidemics of viral infectious diseases. Advances in high-throughput sequencing, including portable genomic sequencing at reduced costs and turnaround time, are paralleled by continuing developments in methodology to infer evolutionary histories (dynamics/patterns) and to identify factors driving viral spread in space and time. The traditionally static nature of visualizing phylogenetic trees that represent these evolutionary relationships/processes has also evolved, albeit perhaps at a slower rate. Advanced visualization tools with increased resolution assist in drawing conclusions from phylogenetic estimates and may even have potential to better inform public health and treatment decisions, but the design (and choice of what analyses are shown) is hindered by the complexity of information embedded within current phylogenetic models and the integration of available meta-data. In this review, we discuss visualization challenges for the interpretation and exploration of reconstructed histories of viral epidemics that arose from increasing volumes of sequence data and the wealth of additional data layers that can be integrated. We focus on solutions that address joint temporal and spatial visualization but also consider what the future may bring in terms of visualization and how this may become of value for the coming era of real-time digital pathogen surveillance, where actionable results and adequate intervention strategies need to be obtained within days.

negative: Detection and isolation of asymptomatic individuals can make the difference in COVID-19 epidemic management Mathematical modeling of infectious diseases is a powerful tool for the design of management policies and a fundamental part of the arsenal currently deployed to deal with the COVID-19 pandemic. Here we present a compartmental model for the disease that can provide healthcare burden parameters allowing to infer possible containment and suppression strategies, explicitly including asymptomatic individuals. The main conclusion of our work is that efficient and timely detection and isolation of these asymptomatic individuals can have dramatic effects on the effective reproduction number and healthcare burden parameters. This intervention can provide a valuable tool complementary to other non-pharmaceutical interventions to contain the epidemic.

negative: COVID 19 and Spanish flu pandemics: All it changes, nothing changes. The Corona Virus 19 (COVID 19) epidemic is an infectious disease which was declared as a pandemic and hit all the Countries, all over the world, from the beginning of the year 2020. There are many similarities between the COVID 19 epidemic and the Spanish flu epidemic. We considered some preventive measures which do not change in the two epidemics.

negative: The epidemiology and clinical characteristics of co-infection of SARS-CoV-2 and influenza viruses in patients during COVID-19 outbreak In this study, we performed a single-centered study of 307 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. It was found that co-infection of SARS-CoV-2 and influenza virus was common during COVID-19 outbreak. And patients coinfected with SARS-CoV-2 and influenza B virus have a higher risk of developing poor outcomes so a detection of both viruses was recommended during COVID-19 outbreak.

negative: Revisiting the 1957 and 1968 influenza pandemics

negative: Smart technologies for fighting pandemics: The techno- and human- driven approaches in controlling the virus transmission Abstract How do governments in China and Western democracies differ in their technological response to control the transmission of the pandemic? Based on an analysis of academic papers, World Health Organization reports and newspapers, this research compares two opposing approaches, whereas the Chinese cities and government have adopted a techno-driven approach, Western governments have adopted a human-driven approach to control the transmission of Covid-19. The findings highlight that although the techno driven approach may be more productive to identify, isolate and quarantine infected individuals, it also results in the suppression and censoring the citizen views. It is further emphasized that human interaction with the technology is mediated by the political and institutional context in which the technologies are implemented. This paper contributes to literature by understanding the human-technology relationship, and offers five practical observations for controlling virus transmissions during pandemics.

negative: Assessment of 10-nm Particle Number (PN) Portable Emissions Measurement Systems (PEMS) for Future Regulations The particle number (PN) emissions of vehicles equipped with particulate filters are low. However, there are technologies that can have high PN levels, especially below the currently lower regulated particle size of 23 nm. Sub-23-nm particles are also considered at least as dangerous as the larger ultrafine particles. For this reason, the European Union (EU) is planning to regulate particles down to 10 nm. In this study we compared prototype portable emission measurement systems (PEMS) and reference laboratory systems measuring from 10 nm. The tests included cycles and constant speeds, using vehicles fuelled with diesel, gasoline or liquefied petroleum gas (LPG). The results showed that the PEMS were within ±40% of the reference systems connected to the tailpipe and the dilution tunnel. Based on the positive findings and the detection efficiencies of the prototype instruments, a proposal for the technical specifications for the future regulation was drafted.

negative: Chapter 31 Coronaviruses Abstract Coronaviruses possess a distinctive morphology, the name being derived from the outer fringe, or “corona” of embedded envelope protein. Members of the family Coronaviridae cause a broad spectrum of animal and human diseases. Uniquely, replication of the RNA genome proceeds through the generation of a nested set of viral mRNA molecules. Until 2003, coronaviruses attracted little interest beyond causing mild upper respiratory tract infections. This changed dramatically in 2003 with the zoonotic SARS-CoV and the more recent emergence of MERS-CoV has confirmed the coronaviruses as significant causes of severe respiratory disease.

negative: $\alpha$-Satellite: An AI-driven System and Benchmark Datasets for Hierarchical Community-level Risk Assessment to Help Combat COVID-19 The novel coronavirus and its deadly outbreak have posed grand challenges to human society: as of March 26, 2020, there have been 85,377 confirmed cases and 1,293 reported deaths in the United States; and the World Health Organization (WHO) characterized coronavirus disease (COVID-19) - which has infected more than 531,000 people with more than 24,000 deaths in at least 171 countries - a global pandemic. A growing number of areas reporting local sub-national community transmission would represent a significant turn for the worse in the battle against the novel coronavirus, which points to an urgent need for expanded surveillance so we can better understand the spread of COVID-19 and thus better respond with actionable strategies for community mitigation. By advancing capabilities of artificial intelligence (AI) and leveraging the large-scale and real-time data generated from heterogeneous sources (e.g., disease related data from official public health organizations, demographic data, mobility data, and user geneated data from social media), in this work, we propose and develop an AI-driven system (named $\alpha$-Satellite}, as an initial offering, to provide hierarchical community-level risk assessment to assist with the development of strategies for combating the fast evolving COVID-19 pandemic. More specifically, given a specific location (either user input or automatic positioning), the developed system will automatically provide risk indexes associated with it in a hierarchical manner (e.g., state, county, city, specific location) to enable individuals to select appropriate actions for protection while minimizing disruptions to daily life to the extent possible. The developed system and the generated benchmark datasets have been made publicly accessible through our website. The system description and disclaimer are also available in our website.

negative: Pandemic Influenza Planning, United States, 1978–2008 During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community’s response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises.

negative: The role of the hotel industry in the response to emerging epidemics: a case study of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong BACKGROUND: The global travel and tourism industry has been rapidly expanding in the past decades. The traditional focus on border screening, and by airline and cruise industries may be inadequate due to the incubation period of an infectious disease. This case study highlights the potential role of the hotel industry in epidemic preparedness and response. METHODS: This case study focuses on the epidemic outbreaks of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong, and the subsequent guidelines published by the health authority in relation to the hotel industry in Hong Kong which provide the backbone for discussion. RESULTS: The Metropole Hotel hastened the international spread of the 2003 SARS outbreak by the index case infecting visitors from Singapore, Vietnam, Canada as well as local people via close contact with the index case and the environmental contamination. The one-week quarantine of more than 300 guests and staff at the Metropark Hotel during the 2009 H1N1 swine flu exposed gaps in the partnership with the hotel industry. The subsequent guidelines for the hotel industry from the Centre of Health Protection focused largely on the maintenance of hygiene within the hotel premises. CONCLUSION: Positive collaborations may bring about effective preparedness across the health and the tourism sectors for future epidemics. Regular hygiene surveillance at hotel facilities, and developing coordination mechanism for impending epidemics on the use of screening, swift reporting and isolation of infected persons may help mitigate the impact of future events. Preparedness and contingency plans for infectious disease control for the hotel industry requires continuous engagement and dialogue.

negative: Airports, localities and disease: Representations of global travel during the H1N1 pandemic Abstract During summer 2009, the UK experienced one of the highest incidences of H1N1 infection outside of the Americas and Australia. Building on existing research into biosecurity and the spread of infectious disease via the global airline network, this paper explores the biopolitics of public health in the UK through an in-depth empirical analysis of the representation of H1N1 in UK national and regional newspapers. We uncover new discourses relating to the significance of the airport as a site for control and the ethics of the treatment of the traveller as a potential transmitter of disease. We conclude by highlighting how the global spread of infectious diseases is grounded in particular localities associated with distinctive notions of biosecurity and the traveller.

negative: Co-infections among patients with COVID-19: the need for combination therapy with non-anti-SARS-CoV-2 agents? Abstract Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.

negative: Gastroenteritis and respiratory infection outbreaks in French nursing homes from 2007 to 2018: Morbidity and all-cause lethality according to the individual characteristics of residents BACKGROUND: Gastroenteritis (GE) and respiratory tract infection (RTI) outbreaks are a significant issue in nursing homes. This study aimed to describe GE and RTI outbreaks with infection and all-cause lethality rates according to the individual characteristics of nursing home residents. METHODS: Clinical and virological surveillance were conducted (2007 to 2018). Virus stratifications for the analysis were: outbreaks with positive norovirus or influenza identifications (respectively NoV+ or Flu+), episodes with no NoV or influenza identification or testing (respectively NoV- or Flu-). Associations between individual variables (sex, age, length of stay (LOS), autonomy status) and infection and lethality rates were tested with univariate and Mantel-Haenszel (MH) methods. RESULTS: 61 GE outbreaks and 76 RTI oubreaks (total 137 outbreaks) were recorded involving respectively 4309 and 5862 residents. In univariate analysis, higher infection rates and age were associated in NoV+, NoV-, and Flu+ contexts, and lower infection rates were associated with longer stays (NoV+ and NoV-). In MH stratified analysis (virus, sex (female/male)) adjusted for LOS (<4 or ≥4 years), the odds of being infected remained significant among older residents (≥86 years): NoV+/male (Odds ratio (OR(MH)): 1.64, 95% confidence interval (CI): 1.16–2.30) and Flu+/female and male (respectively OR(MH): 1.50, CI: 1.27–1.79 and 1.73, CI: 1.28–2.33). In univariate analysis, lower autonomy status (NoV+, Flu+ and Flu-) and increased age (Flu+) were associated with higher lethality. In MH adjusted analysis, significant OR(age) adjusted for autonomy was: Flu+/ ≥86 years compared with <86 years, 1.97 (1.19–3.25) and OR(autonomy) adjusted for age for the more autonomous group (compared with the less autonomous group) was: Flu+, 0.41 (0.24–0.69); Flu-, 0.42 (0.20, 0.90). CONCLUSION: The residents of nursing homes are increasingly elderly and dependent. The specific infection and lethality risks according to these two factors indicate that surveillance and infection control measures are essential and of high priority.

negative: Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010–2012) BACKGROUND: Acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain largely unknown in developing countries. This study represents the first attempt to characterise viral aetiologies of ILIs in Bolivia. METHODS: It was performed in Santa Cruz city from January 2010 to September 2012, based on 564 naso-pharyngeal swabs collected in a National Reference Laboratory and real-time PCR techniques, viral cultures and phylogenetic analyses. RESULTS: 50.2% of samples were positive for at least one virus with influenza viruses (Flu A: ~15%; Flu B: ~9%), rhinoviruses (~8%), coronaviruses (~5%) and hRSV (~4%) being the most frequently identified. The pattern of viral infections varied according to age groups. The elucidation rate was the highest (>60%) amongst patients under 10 yo and the lowest (<40%) amongst patients ≥60 yo. Nearly 3% of samples showed dual viral infections. Epidemiological peaks were associated with a predominant virus but generally included 30-50% of infections by different viruses. Unexpectedly, the frequency of influenza in the 0–4 yo population was very low and a complete hRSV eclipse occurred in 2011. Genetic analyses indicated that distinct evolutionary lineages of Flu A(H1N1)pdm2009, Flu A/H3N2 and Flu B have co-circulated in Bolivia in the study period, originating from Central and North America, Europe, Asia and Australia. CONCLUSION: Our results emphasise the requirement for a reinforced epidemiological and genetic follow-up of influenza and other ILIs in Bolivia to further inform the preparation of vaccines used in the region, guide vaccination campaigns and improve the medical management of patients.

negative: Viral etiology of community-acquired pneumonia among adolescents and adults with mild or moderate severity and its relation to age and severity BACKGROUND: Better knowledge of distribution of respiratory viruses (RVs) in adolescents and adults with community-acquired pneumonia (CAP) is needed. METHODS: To investigate the RVs etiology among adolescents and adults with CAP, according to age and pneumonia severity index (PSI), a multi-center, prospective study was conducted from November 2010 to April 2012. Fifteen RVs were tested by polymerase chain reaction (PCR). Bacteria were detected by urinary antigen, conventional culture and PCR. RESULTS: Mean (SD) age and median (IQR) PSI score of 954 patients enrolled was 45.2 (19.5) years (range 14–94) and 42 (36). RVs were found in 262 patients (27.5%): influenza virus A (IFV A, 9.9%) comprised of pandemic H1N1 (6.7%) and seasonal H3N2 (3.5%), human rhinovirus (4.3%), adenovirus (4.2%), human metapneumovirus (1.8%), parainfluenza virus 1, 3 and 2 (1.7%, 1.5% and 1.2%). Influenza virus B, enterovirus, respiratory syncytial virus, human coronavirus and parainfluenza virus 4 were rarely detected (<1%). Frequency of IFV A was highest among patients aged between 45–64 years (p < 0.001), while adenovirus among patients aged 14–17 years (p < 0.001), no differences was found in other RVs. The proportion of pandemic H1N1 increased with severity of pneumonia evaluated by PSI (P < 0.05). CONCLUSIONS: The proportion of RVs in CAP is higher than previously reported. IFV A pneumonia are usually found in patients older than 45 years, while, adenovirus pneumonia are common in adolescents and young adults. Pandemic H1N1 virus is still recognized by PSI as a high-severity pathogen. The findings contribute baseline data on viral CAP study in China.

negative: Ethnicity and covid-19: analysis must be inclusive and transparent.

negative: Communicable Disease Surveillance Ethics in the Age of Big Data and New Technology Surveillance is essential for communicable disease prevention and control. Traditional notification of demographic and clinical information, about individuals with selected (notifiable) infectious diseases, allows appropriate public health action and is protected by public health and privacy legislation, but is slow and insensitive. Big data–based electronic surveillance, by commercial bodies and government agencies (for profit or population control), which draws on a plethora of internet- and mobile device–based sources, has been widely accepted, if not universally welcomed. Similar anonymous digital sources also contain syndromic information, which can be analysed, using customised algorithms, to rapidly predict infectious disease outbreaks, but the data are nonspecific and predictions sometimes misleading. However, public health authorities could use these online sources, in combination with de-identified personal health data, to provide more accurate and earlier warning of infectious disease events—including exotic or emerging infections—even before the cause is confirmed, and allow more timely public health intervention. Achieving optimal benefits would require access to selected data from personal electronic health and laboratory (including pathogen genomic) records and the potential to (confidentially) re-identify individuals found to be involved in outbreaks, to ensure appropriate care and infection control. Despite existing widespread digital surveillance and major potential community benefits of extending its use to communicable disease control, there is considerable public disquiet about allowing public health authorities access to personal health data. Informed public discussion, greater transparency and an ethical framework will be essential to build public trust in the use of new technology for communicable disease control.

negative: Mysterious Virus: A Review on Behavior and Treatment Approaches of the Novel Coronavirus, 2019-nCoV Abstract At the end of the year 2019, the novel coronavirus (2019-nCoV) was spreading in Wuhan, China, and the outbreak process has a high speed. It was recognized as a pandemic by the World Health Organization (WHO) on 11 March 2020. Coronaviruses are enveloped and single-stranded RNA that have several families including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The pathogenesis mechanism and disease outcomes of SARS and MERS are now clear to some extent, but little information is available for 2019-nCoV. This newly identified corona virus infection represents flu-like symptoms, but usually the first symptoms are fever and dry cough. There has been no specific treatment against 2019-nCoV up to now, and physicians only apply supportive therapy. In the present article, we made an attempt to review the behavior of the virus around the world, epidemiology, a pathway for influx into the host cells, clinical presentation, as well as the treatments currently in use and future approaches; nitazoxanide may be our dream drug. We hope that this review has a positive impact on public knowledge for helping to deal with the 2019-nCoV and move one step forward toward its treatment in the near future.

negative: Lack of seasonal variation of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

negative: Co-circulation of human metapneumovirus and SARS-associated coronavirus during a major nosocomial SARS outbreak in Hong Kong Abstract Background The clinico-epidemiological significance of human metapneumovirus (hMPV) detected during the SARS outbreak is unknown. Objectives To characterize a nosocomial hMPV outbreak during the 2003 SARS epidemic. Study design and methods All available nasopharyngeal aspirate (NPA) collected from confirmed patients during the first 8 weeks of the SARS outbreak in 2003 were tested for hMPV by a nested RT-PCR assay targeting the F-gene. Clinico-epidemiological information was used to analyze the relationship of hMPV co-infection to specific risk factors (demographics/symptoms/outcomes; status as health-care workers (HCWs)/patients; history of exposure/contact; ward location). Multivariate logistic regression analysis was performed to determine independent risk factors. Results An hMPV outbreak occurred during 6–16 March 2003 (first week of the Hong Kong SARS epidemic). hMPV RNA was detected in 31 of 155 (20%) NPAs from SARS patients. HCW status (OR 2.72, 95% CI 1.11–6.68; p =0.029) or epidemiological linkage to the SARS outbreak ward (OR 3.59, 95% CI 1.42–9.05; p =0.007) were independent factors associated with hMPV infection. Symptoms of cough and coryza were more common in co-infected individuals (22.6% vs. 15.9%) but this was not statistically significant. Other clinical manifestations and outcomes were not different in co-infected patients. Conclusions A major nosocomial hMPV outbreak involving HCWs occurred during the early SARS epidemic. Patients with dual hMPV and SARS infection were not sicker than those with SARS infection only.

negative: Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis Abstract Background An outbreak of Novel Coronavirus (COVID -19) in Wuhan, China, the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries. Aims The aim of the meta-analysis was to assess the prevalence of comorbidities in the COVID-19 infection patients and the risk of underlying diseases in severe patients compared to non-severe patients. Methods A literature search was conducted using the databases PubMed, EMBASE, and Web of sciences until February 25, 2020. Risk ratio (OR) and 95% confidence intervals (CIs) were pooled using random-effects models. Results Eight studies were included in the meta- analysis, including 46248 infected patients. The result showed the most prevalent clinical symptom was fever ( 91 ± 3, 95% CI 86-97% ), followed by cough (67 ± 7, 95% CI 59-76%), fatigue ( 51 ± 0, 95% CI 34-68% ) and dyspnea ( 30 ± 4, 95% CI 21-40%). The most prevalent comorbidity were hypertension (17 ± 7, 95% CI 14-22%) and diabetes ( 8 ± 6, 95% CI 6-11% ), followed by cardiovascular diseases ( 5 ± 4, 95% CI 4-7% ) and respiratory system disease( 2 ± 0, 95% CI 1-3% ). Compared with the Non-severe patient, the pooled odds ratio of hypertension, respiratory system disease, cardiovascular disease in severe patients were (OR 2.36, 95% CI: 1.46-3.83), (OR 2.46, 95% CI: 1.76-3.44) and (OR 3.42, 95% CI: 1.88-6.22)respectively. Conclusion We assessed the prevalence of comorbidities in the COVID-19 infection patients and found underlying disease, including hypertension, respiratory system disease and cardiovascular, may be a risk factor for severe patients compared with Non-severe patients.

negative: Aerosol influenza transmission risk contours: A study of humid tropics versus winter temperate zone BACKGROUND: In recent years, much attention has been given to the spread of influenza around the world. With the continuing human outbreak of H5N1 beginning in 2003 and the H1N1 pandemic in 2009, focus on influenza and other respiratory viruses has been increased. It has been accepted for decades that international travel via jet aircraft is a major vector for global spread of influenza, and epidemiological differences between tropical and temperate regions observed. Thus we wanted to study how indoor environmental conditions (enclosed locations) in the tropics and winter temperate zones contribute to the aerosol spread of influenza by travelers. To this end, a survey consisting of 632 readings of temperature (T) versus relative humidity (RH) in 389 different enclosed locations air travelers are likely to visit in 8 tropical nations were compared to 102 such readings in 2 Australian cities, including ground transport, hotels, shops, offices and other publicly accessible locations, along with 586 time course readings from aircraft. RESULTS: An influenza transmission risk contour map was developed for T versus RH. Empirical equations were created for estimating: 1. risk relative to temperature and RH, and 2. time parameterized influenza transmission risk. Using the transmission risk contours and equations, transmission risk for each country's locations was compared with influenza reports from the countries. Higher risk enclosed locations in the tropics included new automobile transport, luxury buses, luxury hotels, and bank branches. Most temperate locations were high risk. CONCLUSION: Environmental control is recommended for public health mitigation focused on higher risk enclosed locations. Public health can make use of the methods developed to track potential vulnerability to aerosol influenza. The methods presented can also be used in influenza modeling. Accounting for differential aerosol transmission using T and RH can potentially explain anomalies of influenza epidemiology in addition to seasonality in temperate climates.

negative: An ecological study of socioeconomic predictors in detection of COVID-19 cases across neighborhoods in New York City Abstract Background: New York City was the first major urban center of the COVID-19 pandemic in the USA. Cases are clustered in the city, with certain neighborhoods experiencing more cases than others. We investigate whether potential socioeconomic factors can explain between-neighborhood variation in the number of detected COVID-19 cases. Methods: Data were collected from 177 Zip Code Tabulation Areas (ZCTA) in New York City (99.9% of the population). We fit multiple Bayesian Besag-York-Mollié (BYM) mixed models using positive COVID-19 tests as the outcome and a set of 10 representative economic, demographic, and health-care associated ZCTA-level parameters as potential predictors. The BYM model includes both spatial and nonspatial random effects to account for clustering and overdispersion. Results: Multiple different regression approaches indicated a consistent, statistically significant association between detected COVID-19 cases and dependent (under 18 or 65+ years old) population, male to female ratio, and median household income. In the final model, we found that an increase of only 1% in dependent population is associated with a 2.5% increase in detected COVID-19 cases (95% confidence interval (CI): 1.6% to 3.4%, p < 0.0005). An increase of 1 male per 100 females is associated with a 1.0% (95% CI: 0.6% to 1.5%, p < 0.0005) increases in detected cases. A decrease of $10,000 median household income is associated with a 2.5% (95% CI: 1.0% to 4.1% p = 0.002) increase in detected COVID-19 cases. Conclusions: Our findings indicate associations between neighborhoods with a large dependent population, those with a high proportion of males, and low-income neighborhoods and detected COVID-19 cases. Given the elevated mortality in aging populations, the study highlights the importance of public health management during and after the current COVID-19 pandemic. Further work is warranted to fully understand the mechanisms by which these factors may have affected the number of detected cases, either in terms of the true number of cases or access to testing.

negative: Longitudinal active sampling for respiratory viral infections across age groups BACKGROUND: Respiratory viral infections are a major cause of morbidity and mortality worldwide. However, their characterization is incomplete because prevalence estimates are based on syndromic surveillance data. Here, we address this shortcoming through the analysis of infection rates among individuals tested regularly for respiratory viral infections, irrespective of their symptoms. METHODS: We carried out longitudinal sampling and analysis among 214 individuals enrolled at multiple New York City locations from fall 2016 to spring 2018. We combined personal information with weekly nasal swab collection to investigate the prevalence of 18 respiratory viruses among different age groups and to assess risk factors associated with infection susceptibility. RESULTS: 17.5% of samples were positive for respiratory viruses. Some viruses circulated predominantly during winter, whereas others were found year round. Rhinovirus and coronavirus were most frequently detected. Children registered the highest positivity rates, and adults with daily contacts with children experienced significantly more infections than their counterparts without children. CONCLUSION: Respiratory viral infections are widespread among the general population with the majority of individuals presenting multiple infections per year. The observations identify children as the principal source of respiratory infections. These findings motivate further active surveillance and analysis of differences in pathogenicity among respiratory viruses.

negative: The COVID-19 pandemic and research shutdown: staying safe and productive

negative: Comparison of clinical characteristics of coronavirus disease (COVID-19) and severe acute respiratory syndrome (SARS) as experienced in Taiwan • From our data, we know 2019-nCoV invades more common in male, not likely the SARS that is female predominant. • The 2019-nCoV patients are around 20 years older than the population of SARS. Young adults are susceptible to SARS than the children and elderly. • Hypoalbuminemia are noted in SARS patients, it needs a longer time to study whether the 2019-nCoV possesses the same presentation.

negative: Chapter 21 Use of Host Factors in Microbial Forensics Publisher Summary This chapter illustrates central elements of the host response in a simplified fashion and describes a few representative examples that have a high potential of providing evidence. It may aid an investigation to distinguish a perpetrator from a victim who has been exposed to a particular microorganism or by-product, such as a toxin. Considerable advances have been made in the forensic analysis of microbes and toxins. These advances include sequencing, genomics, and microscopy. An underdeveloped and underutilized area in microbial forensics is how the host interacts with microorganisms in a way that provides unique signatures for forensic use. For investigative and forensic purposes, an immediate goal is to distinguish a potential victim and innocent person from a perpetrator and to distinguish between a naturally acquired or intentional infection. Two principal methods that are sufficiently developed are characterization of the humoral immune response and identification of vaccine-induced immunity or antibiotics that may be present in a possible perpetrator. The primary aims of a microbial forensics investigation are to identify the biological agent, its source, and the individuals responsible for the event. Analytic approaches differ when the suspected biothreat agent is encountered in a container or the environment, as opposed to in vivoin a human, animal, or plant. Analyses of trace elements, pollens, growth media, latent fingerprints, and microbial and nonmicrobial nucleic acids are all applicable to the container and environmental sample.

negative: A simple mathematical model for Coronavirus (COVID-19) A novel coronavirus (COVID-19) was identified in Wuhan, China in the end of 2019, it causing an outbreak of viral pneumonia. It caused to the death rate of 4:63% among 571; 678 confirmed cases around the world to the March 28th, 2020. In this brief current study, we will present a simple mathematical model where we show how the probability of successfully getting infected when coming into contact with an infected individual and the per capita contact rate affect the healthy and infected population with time. The proposed model is used to offer predictions about the behavior of COVID-19 for a shorter period of time.

negative: Deep Multimodal Clustering with Cross Reconstruction Recently, there has been surging interests in multimodal clustering. And extracting common features plays a critical role in these methods. However, since the ignorance of the fact that data in different modalities shares similar distributions in feature space, most works did not mining the inter-modal distribution relationships completely, which eventually leads to unacceptable common features. To address this issue, we propose the deep multimodal clustering with cross reconstruction method, which firstly focuses on multimodal feature extraction in an unsupervised way and then clusters these extracted features. The proposed cross reconstruction aims to build latent connections among different modalities, which effectively reduces the distribution differences in feature space. The theoretical analysis shows that the cross reconstruction reduces the Wasserstein distance of multimodal feature distributions. Experimental results on six benchmark datasets demonstrate that our method achieves obviously improvement over several state-of-arts.

negative: Are dental schools adequately preparing dental students to face outbreaks of infectious diseases such as COVID‐19? The recent 2019‐novel coronavirus (2019‐nCoV, also known as SARS‐CoV‐2) has caused >2,622,571 confirmed cases of coronavirus disease 2019 (COVID‐19) in >185 countries, and >182,359 deaths globally. More than 9000 healthcare workers have also been infected by 2019‐nCoV. Prior to the present pandemic of COVID‐19, there have been multiple large‐scale epidemics and pandemics of other viral respiratory infections, such as seasonal flu, Spanish flu (H1N1), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and others. Dental professionals are at an increased risk for contracting these viruses from dental patients, as dental practice involves face‐to‐face communication with the patients and frequent exposure to saliva, blood, and other body fluids. Dental education can play an important role in the training of dentists, helping them to adopt adequate knowledge and attitudes related to infection control measures. The current dental curriculum does not cover infection control adequately, especially from airborne pathogens. Infection control education needs to be included in the dental curriculum itself, and students should be trained adequately to protect them and prevent the infection from disseminating even before they see their first patient.

negative: Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes double-stranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections.

negative: Covid‐19 diffusion and its impact on dental practice in distant countries with similar ethnic background Epidemiology of Covid‐19 and diffusion patterns of the novel coronavirus (SARS – CoV – 2) are still poorly understood, as they differ substantially among countries and even in neighboring regions within the same country. It is not clear if differences in viral spreading depends on population age, genetic influences, specific environmental factors (e.g. season of the year), socioeconomic conditions or a combination of these. Some Authors hypothesized that differences in models of SARS – CoV – 2 diffusion may be explained also on the basis of ethnic influences (Pareek, Bangash, Pareek, Pan, Sze, Minhas, Hanif, Khunti, 2020). Under such perspective, it seems rational to compare the Italian experience to that of Uruguay.

negative: Enhancing the legitimacy of public health response in pandemic influenza planning: lessons from SARS.

negative: Research agenda on persistent and unpredictable threat of influenza and emerging respiratory infections: a public health necessity in the Eastern Mediterranean Region (Guest Editorial). Infectious diseases continue to represent a significant threat to global health security, particularly in the context of increasing globalization, interconnectedness and interdependence. Chief among such threats are influenza viruses and other respiratory pathogens, such as Middle East Respiratory Syndrome coronavirus (MERS-CoV), because of their risk of high transmissibility and acuity of illness. Annual epidemics of seasonal influenza cause an estimated 3-5 million cases of severe illness and more than 500 000 deaths, with the prospect of pandemic influenza viruses causing far greater impact. In addition, the appearance of severe acute respiratory syndrome (SARS) in 2003, widespread and continued outbreaks of avian influenza A (H5N1) since 2004, the H1N1 pandemic in 2009 and emergence of MERS CoV in 2012 reflect the seriousness of public health challenges posed by influenza and emerging respiratory infections.

negative: Development of a multiplex one step RT-PCR that detects eighteen respiratory viruses in clinical specimens and comparison with real time RT-PCR Abstract Rapid and accurate diagnosis of viral respiratory infections is crucial for patient management. Multiplex reverse transcriptase polymerase chain reaction (mRT-PCR) is used increasingly to diagnose respiratory infections and has shown to be more sensitive than viral culture and antigen detection. Objective of the present study was to develop a one-step mRT-PCR that could detect 18 respiratory viruses in three sets. The method was compared with real time RT-PCR (rRT-PCR) for its sensitivity and specificity. Clinical specimens from 843 pediatric patients with respiratory symptoms were used in the study. 503 (59.7%) samples were detected positive by mRT-PCR. Of these 462 (54.8%) exhibited presence of a single pathogen and 41 (4.9%) had multiple pathogens. rRT-PCR detected 439 (52.1%) positive samples, where 419 (49.7%) exhibited one virus and 20 (2.4%) showed co-infections. Concordance between mRT-PCR and rRT-PCR was 91.9% and kappa correlation 0.837. Sensitivity and specificity of mRT-PCR were 99.5% and 83.7% while that of rRT-PCR was 86.9% and 99.4% respectively. Rhinovirus (17.2%) was the most frequently detected virus followed by respiratory syncytial virus B (15.4%), H1N1pdm09 (8.54%), parainfluenza virus-3 (5.8%) and metapneumovirus (5.2%). In conclusion, mRT-PCR is a rapid, cost effective, specific and highly sensitive method for detection of respiratory viruses.

negative: The short-term seasonal analyses between atmospheric environment and COVID-19 in epidemic areas of Cities in Australia, South Korea, and Italy The impact of the outbreak of COVID-19 on health has been widely concerned. Disease risk assessment, prediction, and early warning have become a significant research field. Previous research suggests that there is a relationship between air quality and the disease. This paper investigated the impact of the atmospheric environment on the basic reproduction number (R$_0$) in Australia, South Korea, and Italy by using atmospheric environment data, confirmed case data, and the distributed lag non-linear model (DLNM) model based on Quasi-Poisson regression. The results show that the air temperature and humidity have lag and persistence on short-term R$_0$, and seasonal factors have an apparent decorating effect on R$_0$. PM$_{10}$ is the primary pollutant that affects the excess morbidity rate. Moreover, O$_3$, PM$_{2.5}$, and SO$_2$ as perturbation factors have an apparent cumulative effect. These results present beneficial knowledge for correlation between environment and COVID-19, which guiding prospective analyses of disease data.

negative: Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections BACKGROUND: Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection. METHODS: To evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured. RESULTS: The high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization. CONCLUSIONS: The present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections.

negative: Impact of influenza-like illness and effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy Abstract In order to evaluate the impact of influenza-like illness and the effectiveness of influenza vaccination in children with oncohematological disease who have completed cancer therapy, 182 children with a diagnosis of oncohematological disease were divided into two subgroups on the basis of the length of time off therapy (<6 months or 6–24 months) and randomised 1:1 to receive influenza vaccination or not. The controls were 91 otherwise healthy children unvaccinated against influenza. The results show that the clinical and socioeconomic impact of influenza-like illnesses and the effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy are related to the length of the off therapy period, and seem to be significantly greater in those who have been off therapy for less than 6 months in comparison with healthy controls. This suggests that the administration of influenza vaccination should be strongly recommended only among oncohematological children who have been off therapy for less than 6 months.

negative: Community pharmacists and communication in the time of COVID-19: Applying the health belief model Abstract The emergence of the novel coronavirus disease (COVID-19) pandemic presents an unprecedented health communications challenge. Healthcare providers should reinforce behaviors that limit the spread of the pandemic, including social distancing and remaining in the home whenever possible. Formal communications toolkits may not be prepared in a timely fashion. Community pharmacists can reinforce mitigation behaviors by applying the health belief model (HBM). This commentary provides an overview of the HBM and offers suggestions on how community pharmacists can use it as a guide to patient communication in these uncertain contexts.

negative: Silver lining of COVID-19: Heightened global interest in pneumococcal and influenza vaccines, an infodemiology study BACKGROUND: Health-seeking behaviors change during pandemics and may increase with regard to illnesses with symptoms similar to the pandemic. The global reaction to COVID-19 may drive interest in vaccines for other diseases. OBJECTIVES: Our study investigated the correlation between global online interest in COVID-19 and interest in CDC-recommended routine vaccines. DESIGN, SETTINGS, MEASUREMENTS: This infodemiology study used Google Trends data to quantify worldwide interest in COVID-19 and CDC-recommended vaccines using the unit search volume index (SVI), which estimates volume of online search activity relative to highest volume of searches within a specified period. SVIs from December 30, 2019 to March 30, 2020 were collected for "coronavirus (Virus)" and compared with SVIs of search terms related to CDC-recommended adult vaccines. To account for seasonal variation, we compared SVIs from December 30, 2019 to March 30, 2020 with SVIs from the same months in 2015 to 2019. We performed country-level analyses in ten COVID-19 hotspots and ten countries with low disease burden. RESULTS: There were significant positive correlations between SVIs for "coronavirus (Virus)" and search terms for pneumococcal (R = 0.89, p < 0.0001) and influenza vaccines (R = 0.93, p < 0.0001) in 2020, which were greater than SVIs for the same terms in 2015-2019 (p = 0.005, p < 0.0001, respectively). Eight in ten COVID-19 hotspots demonstrated significant positive correlations between SVIs for coronavirus and search terms for pneumococcal and influenza vaccines. LIMITATIONS: SVIs estimate relative changes in online interest and do not represent the interest of people with no Internet access. CONCLUSION: A peak in worldwide interest in pneumococcal and influenza vaccines coincided with the COVID-19 pandemic in February and March 2020. Trends are likely not seasonal in origin and may be driven by COVID-19 hotspots. Global events may change public perception about the importance of vaccines. Our findings may herald higher demand for pneumonia and influenza vaccines in the upcoming season.

negative: La grippe saisonnière Résumé La grippe saisonnière est due aux virus influenza A et B. Il s’agit de virus enveloppés dont le génome est constitué de sept à huit fragments d’ARN. Les différents sous-types sont déterminés par la nature des deux glycoprotéines de surface HA et NA. La grippe saisonnière est une maladie épidémique et hivernale dans les zones à climat tempéré. Son épidémiologie est liée à la grande variabilité du virus au cours du temps, nécessitant la mise en place d’un système d’alerte détectant chaque année les variants circulants dominant et déterminant la composition vaccinale. Les symptômes cliniques de la grippe ne sont pas suffisamment spécifiques pour permettre le diagnostic sans examen virologique. Cela est particulièrement vrai en période non épidémique, chez les sujets de plus de 65 ans et chez les enfants de moins de cinq ans. L’enfant représente une cible privilégiée des infections à virus influenza. Le recours à l’hospitalisation est d’autant plus élevé que l’enfant est jeune. Chez le nourrisson, l’infection peut être paucisymptomatique et s’accompagner de manifestations non respiratoires (léthargie, convulsions, malaises). Le diagnostic virologique de la grippe est justifié chez tous les sujets hospitalisés pour un syndrome respiratoire compatible avec une infection à virus influenza. Il existe plusieurs outils permettant une recherche directe du virus dans les sécrétions respiratoires : isolement du virus en culture, détection d’antigènes, détection moléculaire de l’ARN. Le choix de la méthode se fait selon les caractéristiques du test : sensibilité, spécificité, rapidité et simplicité de réalisation, coût. Abstract Seasonal flu is caused by influenza viruses A and B. These enveloped viruses have a genome made up of seven or eight RNA fragments. The different subtypes are determined by the nature of the two surface glycoproteins HA and NA. Seasonal flu is an epidemic wintertime illness occurring in temperate climate zones. Its epidemiology is linked to the great variability of the virus in time, necessitating an alert system that detects dominating circulating variants each year and that determines the vaccination composition. Clinical flu symptoms are not sufficiently specific to allow for diagnosis with virological tests. This is especially true during non-epidemic periods as well as in subjects older than 65 and younger than five. Children are especially vulnerable to influenza virus infections. Hospitalization occurs more frequently, the younger the child. In children younger than two years, the infection can be pauci-symptomatic and is sometimes detected from non-respiratory symptoms such as lethargy, convulsions, and dizziness. In all cases of respiratory syndrome compatible with influenza virus infection in hospitalized subjects, virological flu diagnosis is of utmost interest. Several tools are available to allow for direct viral detection in respiratory specimens: cell culture isolation, antigenic detection, RNA molecular detection. Choice of method is based on the characteristics of the test: sensibility, specificity, speed and ease of realization, and cost.

negative: Replication of a bovine coronavirus in organ cultures of foetal trachea Abstract A strain of bovine coronavirus (BC) adapted to tissue culture, was inoculated into organ cultures of bovine foetal trachea. Haemagglutinin in the fluid from infected organ cultures reached titres of 32 and characteristic coronavirus particles were observed electron microscopically. BC virus antigen was detected in frozen sections of the organ cultures by staining with fluorescent antibody. These data were evidence that BC virus replicated in organ cultures of respiratory tissue. The use of this technique for primary isolation of bovine coronaviruses from field material is discussed.

negative: The novel Coronavirus (SARS-CoV-2) is a one health issue

negative: Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.

negative: Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial BACKGROUND: Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN: Randomized controlled prevention trial with three parallel groups. SETTING: Madison, Wisconsin, USA. PARTICIPANTS: Community-recruited adults who did not regularly exercise or meditate. METHODS: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS: Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS: This trial was likely underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01654289

negative: Etiology and Clinical Outcomes of Acute Respiratory Virus Infection in Hospitalized Adults BACKGROUND: Etiologies and clinical profiles of acute respiratory viral infections need to be clarified to improve preventive and therapeutic strategies. MATERIALS AND METHODS: A retrospective observational study at a single, university-affiliated center was performed to evaluate the respiratory viral infection etiologies in children compared to that in adults and to document the clinical features of common viral infections for adults from July 2009 to April 2012. RESULTS: The common viruses detected from children (2,800 total patients) were human rhinovirus (hRV) (31.8%), adenovirus (AdV) (19.2%), respiratory syncytial virus (RSV) A (17.4%), RSV B (11.7%), and human metapneumovirus (hMPV) (9.8%). In comparison, influenza virus A (IFA) had the highest isolation rate (28.5%), followed by hRV (15.5%), influenza virus B (IFB) (15.0%), and hMPV (14.0%), in adults (763 total patients). Multiple viruses were detected in single specimens from 22.4% of children and 2.0% of adults. IFA/IFB, RSV A/B, and hMPV exhibited strong seasonal detection and similar circulating patterns in children and adults. Adult patients showed different clinical manifestations according to causative viruses; nasal congestion and rhinorrhea were more common in hRV and human coronavirus (hCoV) infection. Patients with RSV B, hRV, or AdV tended to be younger, and those infected with RSV A and hMPV were likely to be older. Those with RSV A infection tended to stay longer in hospital, enter the intensive care unit more frequently, and have a fatal outcome more often. The bacterial co-detection rate was 26.5%, and those cases were more likely to have lower respiratory tract involvement (P = 0.001), longer hospital stay (P = 0.001), and higher mortality (P = 0.001). CONCLUSIONS: The etiologic virus of an acute respiratory infection can be cautiously inferred based on a patient's age and clinical features and concurrent epidemic data. Large-scale prospective surveillance studies are required to provide more accurate information about respiratory viral infection etiology, which could favorably influence clinical outcomes.

negative: An Overview of the Most Significant Zoonotic Viral Pathogens Transmitted from Animal to Human in Saudi Arabia Currently, there has been an increasing socioeconomic impact of zoonotic pathogens transmitted from animals to humans worldwide. Recently, in the Arabian Peninsula, including in Saudi Arabia, epidemiological data indicated an actual increase in the number of emerging and/or reemerging cases of several viral zoonotic diseases. Data presented in this review are very relevant because Saudi Arabia is considered the largest country in the Peninsula. We believe that zoonotic pathogens in Saudi Arabia remain an important public health problem; however, more than 10 million Muslim pilgrims from around 184 Islamic countries arrive yearly at Makkah for the Hajj season and/or for the Umrah. Therefore, for health reasons, several countries recommend vaccinations for various zoonotic diseases among preventive protocols that should be complied with before traveling to Saudi Arabia. However, there is a shortage of epidemiological data focusing on the emerging and reemerging of zoonotic pathogens transmitted from animal to humans in different densely populated cities and/or localities in Saudi Arabia. Therefore, further efforts might be needed to control the increasing impacts of zoonotic viral disease. Also, there is a need for a high collaboration to enhance the detection and determination of the prevalence, diagnosis, control, and prevention as well as intervention and reduction in outbreaks of these diseases in Saudi Arabia, particularly those from other countries. Persons in the health field including physicians and veterinarians, pet owners, pet store owners, exporters, border guards, and people involved in businesses related to animal products have adopted various preventive strategies. Some of these measures might pave the way to highly successful prevention and control results on the different transmission routes of these viral zoonotic diseases from or to Saudi Arabia. Moreover, the prevention of these viral pathogens depends on socioeconomic impacts, available data, improved diagnosis, and highly effective therapeutics or prophylaxis.

negative: Wet markets—a continuing source of severe acute respiratory syndrome and influenza? Summary Context Live-animal markets (wet markets) provide a source of vertebrate and invertebrate animals for customers in tropical and subtropical regions of the world. Wet markets sell live poultry, fish, reptiles, and mammals of every kind. Live-poultry markets (mostly chicken, pigeon, quail, ducks, geese, and a wide range of exotic wild-caught and farm-raised fowl) are usually separated from markets selling fish or red-meat animals, but the stalls can be near each other with no physical separation. Despite the widespread availability of affordable refrigeration, many Asian people prefer live animals for fresh produce. Wet markets are widespread in Asian countries and in countries where Asian people have migrated. Live-poultry markets were the source of the H5N1 bird-influenza virus that transmitted to and killed six of 18people in Hong Kong. Starting point Yi Guan and colleagues (Science 2003; 302: 276–78) recently reported the isolation of severe acute respiratory syndrome (SARS) coronavirus (CoV) from Himalayan palm civets (Paguna larvata) in wet markets in Shenzen, southern China. These researchers also found serological evidence of infection in raccoon dogs (Nyctereutes pro-cuyoinboides). Serological evidence for SARS CoV in human beings working in these markets, taken together with the earliest cases of SARS in restaurant workers, supports the contention of a potential zoonotic origin for SARS. Where next? Will SARS reappear? This question confronts public-health officials worldwide, particularly infectious disease personnel in those regions of the world most affected by the disease and the economic burden of SARS, including China, Taiwan, and Canada. Will the virus re-emerge from wet markets or from laboratories working with SARS CoV, or are asymptomatic infections ongoing in human beings? Similar questions can be asked about a pandemic of influenza that is probably imminent. Knowledge of the ecology of influenza in wet markets can be used as an early-warning system to detect the reappearance of SARS or pandemic influenza.

negative: Increased Risk of Noninfluenza Respiratory Virus Infections Associated With Receipt of Inactivated Influenza Vaccine We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.

negative: Rethinking the Gendered Dimensions in the Impacts and Response to COVID-19 Pandemic Abstract The outbreak of the novel coronavirus disease 2019 (COVID-19) has demonstrated the urgency to rethink the health system quality to efficiently support and improve global health. Whilst efforts are now gathering pace in response to the deleterious impacts of COVID-19, gendered analysis of these impacts and response to the pandemic has been far too little. A critical consideration of gendered lenses and the respective brunt of health crises of the pandemic on men and women can improve our understanding and direction of efforts toward building robust and equitable public health response. Strategic plans for preparedness must be fully grounded in strong gender analysis in the remit of gender roles and norms, and strengthen the leadership and resourceful participation of women in the decision-making process toward addressing COVID-19 outbreak.

negative: The outbreak of COVID-19 coronavirus and its impact on global mental health. BACKGROUND The current outbreak of COVID-19 coronavirus infection among humans in Wuhan (China) and its spreading around the globe is heavily impacting on the global health and mental health. Despite all resources employed to counteract the spreading of the virus, additional global strategies are needed to handle the related mental health issues. METHODS Published articles concerning mental health related to the COVID-19 outbreak and other previous global infections have been considered and reviewed. COMMENTS This outbreak is leading to additional health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear globally. Collective concerns influence daily behaviors, economy, prevention strategies and decision-making from policy makers, health organizations and medical centers, which can weaken strategies of COVID-19 control and lead to more morbidity and mental health needs at global level.

negative: Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks BACKGROUND: As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. METHODS: Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. RESULTS: The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. CONCLUSIONS: These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities.

negative: Severe Illnesses Associated With Outbreaks of Respiratory Syncytial Virus and Influenza in Adults BACKGROUND: Recent reports have described the contribution of adult respiratory syncytial virus (RSV) infections to the use of advanced healthcare resources and death. METHODS: Data regarding patients aged ≥18 years admitted to any of Maryland’s 50 acute-care hospitals were evaluated over 12 consecutive years (2001–2013). We examined RSV and influenza (flu) surveillance data from the US National Respiratory and Enteric Virus Surveillance System and the Centers for Disease Control and Prevention and used this information to define RSV and flu outbreak periods in the Maryland area. Outbreak periods consisted of consecutive individual weeks during which at least 10% of RSV and/or flu diagnostic tests were positive. We examined relationships of RSV and flu outbreaks to occurrence of 4 advanced medical outcomes (hospitalization, intensive care unit admission, intubated mechanical ventilation, and death) due to medically attended acute respiratory illness (MAARI). RESULTS: Occurrences of all 4 MAARI-related hospital advanced medical outcomes were consistently greater for all adult ages during RSV, flu, and combined RSV–flu outbreak periods compared to nonoutbreak periods and tended to be greatest in adults aged ≥65 years during combined RSV–flu outbreak periods. Rate ratios for all 4 MAARI-related advanced medical outcomes ranged from 1.04 to 1.38 during the RSV, flu, or combined RSV–flu outbreaks compared to the nonoutbreak periods, with all 95% lower confidence limits >1. CONCLUSIONS: Both RSV and flu outbreaks were associated with surges in MAARI-related advanced medical outcomes (hospitalization, intensive care unit admission, intubated mechanical ventilation, and death) for adults of all ages.

negative: Community's compliance with measures for the prevention of respiratory infections in Riyadh, Saudi Arabia BACKGROUND: Acute respiratory tract infections are the most common causes of both morbidity and mortality worldwid, and the management and prevention of acute respiratory infections is a global problem, especially in developing countries. This study sought to assess the community's compliance and practice of measures for the prevention of respiratory infections and discover their source of health information. MATERIALS AND METHODS: A cross-sectional study was carried out in the five biggest shopping malls in Riyadh city in July 2014. The required sample size was 980 persons aged 15 or older, with 196 from each of the five biggest shopping malls from each of the five geographic areas of Riyadh. Data was collected by face-to-face interview using standardised questionnaire, and analyzed using SPSS. RESULTS: Overall, 48.3% of the participants thought that they were susceptible to any of the respiratory infections of pandemic influenza; 59.7% always washed their hands with water and soap and 34.8% used antibacterial soap. About 29% reported avoiding touching their eyes, noses, and mouths directly with their hands; 63.5% covered their noses and mouths with tissue paper when sneezing or coughing. A substantial number said they “never” shared their personal stuff, including towels (70.5%) and utensils (49.0%) with others. Only 21.2% avoided crowded places or wore a mask (9.1%) in such a situation. A high proportion (62.8%) did not take the seasonal flu vaccine. The most common sources of health information included television/radio (47.9%), social media (29.4%), and friends/family (28.1%). CONCLUSIONS: Health authorities should seize every opportunity to prevent respiratory infections by adopting all evidence-based infection control measures to improve public awareness, attitude, and practice.

negative: Development of a realtime RT-PCR assay for the rapid detection of influenza A(H2) viruses Abstract Influenza and other acute respiratory infections are of great concern for public health, causing excessive morbidity and mortality throughout the world. Influenza virus A(H2N2), which caused a pandemic of so called “Asian flu” in 1957 was expelled from the human population by the new pandemic virus subtype H3N2 in 1968, however, influenza A(H2) viruses continue to circulate in wild birds and poultry. The lack of immunity in human population and the continued circulation of influenza A(H2) among animals makes emergence of a new pandemic virus possible. One of the basic techniques of molecular diagnostics of infectious diseases is the realtime polymerase chain reaction (PCR). The aim of this work was to design oligonucleotide primers and probes for the rapid detection of influenza A virus subtype H2 by realtime reverse transcription - polymerase chain reaction (rRT-PCR). Analysis of 539 sequences of influenza A(H2N2) virus hemagglutinin gene from GISAID EpiFlu database revealed conservative regions suitable for use as binding sites for primers and probes. 191 probes were designed and 2 sets of primers and probes (H2-1 and H2-2) were selected for further experimental evaluation. Detection limit of RT-PCR system was 50 copies of DNA per 25 μl reaction when 10-fold dilutions of pCI-neo-H2 plasmid used as template. Analytical specificity of selected sets of primers and probes were tested on wide range of influenza strains and non-influenza respiratory viruses. H2-2 set found to have insufficient specificity detecting seasonal influenza A(H1N1) viruses and was excluded from further analysis. Analytical sensitivity was further tested on vaccine strain A/17/California/66/395 (H2N2) and A/Japan/305/1957 (H2N2), limit of detection for primers-probe set H2-1 was 3.2 (CI95%: 3.07–3.48) lg EID50/ml. Designed primers and probes for the realtime RT-PCR universal detection of influenza A(H2) viruses could be used in clinical trials of vaccines against influenza A(H2) and screening for H2 in cases of unsubtypeable influenza A in humans.

negative: Coronavirus disease 2019 in an orthotopic liver transplant recipient living with human immunodeficiency virus Coronavirus disease 2019 (COVID‐19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can manifest with flu‐like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID‐19‐infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID‐19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well‐controlled HIV who successfully recovered from a mild, flu‐like illness attributed to SARS‐CoV‐2.

negative: Ambulance dispatch calls attributable to influenza A and other common respiratory viruses in the Netherlands (2014‐2016) BACKGROUND: Ambulance dispatches could be useful for syndromic surveillance of severe respiratory infections. We evaluated whether ambulance dispatch calls of highest urgency reflect the circulation of influenza A virus, influenza B virus, respiratory syncytial virus (RSV), rhinovirus, adenovirus, coronavirus, parainfluenzavirus and human metapneumovirus (hMPV). METHODS: We analysed calls from four ambulance call centres serving 25% of the population in the Netherlands (2014‐2016). The chief symptom and urgency level is recorded during triage; we restricted our analysis to calls with the highest urgency and identified those compatible with a respiratory syndrome. We modelled the relation between respiratory syndrome calls (RSC) and respiratory virus trends using binomial regression with identity link function. RESULTS: We included 211 739 calls, of which 15 385 (7.3%) were RSC. Proportion of RSC showed periodicity with winter peaks and smaller interseasonal increases. Overall, 15% of RSC were attributable to respiratory viruses (20% in out‐of‐office hour calls). There was large variation by age group: in <15 years, only RSV was associated and explained 11% of RSC; in 15‐64 years, only influenza A (explained 3% of RSC); and in ≥65 years adenovirus explained 9% of RSC, distributed throughout the year, and hMPV (4%) and influenza A (1%) mainly during the winter peaks. Additionally, rhinovirus was associated with total RSC. CONCLUSION: High urgency ambulance dispatches reflect the burden of different respiratory viruses and might be useful to monitor the respiratory season overall. Influenza plays a smaller role than other viruses: RSV is important in children while adenovirus and hMPV are the biggest contributors to emergency calls in the elderly.

negative: A Two-Tube Multiplex Reverse Transcription PCR Assay for Simultaneous Detection of Sixteen Human Respiratory Virus Types/Subtypes There is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. With an intended application in provincial Centers for Diseases Control and Prevention, in this study, we present a two-tube multiplex RT-PCR assay (two-tube assay) using automatic electrophoresis to simultaneously detect sixteen common respiratory viruses. The specificity and the sensitivity of the assay were tested. The assay could detect 20–200 copies per reaction when each viral type was assayed individually, 2000 copies with 9 premixed viral targets in the multiplexed assay in tube 1, and 200 copies with 8 premixed templates in tube 2. A total of 247 specimens were used to evaluate the two-tube assay, and the results were compared with those obtained from the Luminex xTAG RVP Fast assay. The discordant results were confirmed by sequencing or by the Seeplex RV15 ACE detection kit. There were no false positives, but six false negatives occurred with the two-tube assay. In conclusion, the two-tube assay is demonstrated to have great potential for routine surveillance of respiratory virus infection in China.

negative: Virological surveillance of influenza and other respiratory viruses during six consecutive seasons from 2006 to 2012 in Catalonia, Spain Abstract Most attention is given to seasonal influenza and respiratory syncytial virus outbreaks, but the cumulative burden caused by other respiratory viruses (RV) is not widely considered. The aim of the present study is to describe the circulation of RV in the general population during six consecutive seasons from 2006 to 2012 in Catalonia, Spain. Cell culture, immunofluorescence and PCR-based assays were used for the RV laboratory-confirmation and influenza subtyping. Phylogenetic and molecular characterizations of viral haemagglutinin, partial neuraminidase and matrix 2 proteins were performed from a representative sampling of influenza viruses. A total of 6315 nasopharyngeal samples were collected, of which 64% were laboratory-confirmed, mainly as influenza A viruses and rhinoviruses. Results show the significant burden of viral aetiological agents in acute respiratory infection, particularly in the youngest cases. The study of influenza strains reveals their continuous evolution through either progressive mutations or by segment reassortments. Moreover, the predominant influenza B lineage was different from that included in the recommended vaccine in half of the studied seasons, supporting the formulation and use of a quadrivalent influenza vaccine. Regarding neuraminidase inhibitors resistance, with the exception of the 2007/08 H275Y seasonal A(H1N1) strains, no other circulating influenza strains carrying known resistance genetic markers were found. Moreover, all circulating A(H1N1)pdm09 and A(H3N2) strains finally became genetically resistant to adamantanes. A wide knowledge of the seasonality patterns of the RV in the general population is well-appreciated, but it is a challenge due to the unpredictable circulation of RV, highlighting the value of local and global RV surveillance.

negative: One slip up from a worldwide pandemic Do the risks of a lethal flu virus escaping the lab outweigh the benefits of the research, ask Peter Aldhous and Debora MacKenzie

negative: Genotype and phenotype of COVID-19: Their roles in pathogenesis Abstract COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3′-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses.

negative: COVID‐19 diagnosis and management: a comprehensive review Severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2, a novel coronavirus from the same family as SARS‐CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS‐CoV‐2, coronavirus disease 2019 (COVID‐19), presents flu‐like symptoms which can become serious in high‐risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID‐19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: ‘COVID‐19’, ‘2019‐nCoV’, ‘coronavirus’ and ‘SARS‐CoV‐2’. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID‐19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real‐time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow‐up. To date, there is no evidence of any effective treatment for COVID‐19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence‐based treatment modality.

negative: Avian flu: Are we ready? On the cover, a Shanghai commuter takes precautions during the 2003 avian influenza outbreak. It is nearly 40 years since the last worldwide influenza pandemic, and though these things don't run to an orderly timetable, many believe that it is only a matter of time — not much time at that — until the next one. This adds to the public health implications of the recent avian influenza outbreaks in Hong Kong in 1997, 1998 and 2002/3, and the continuing spread of avian influenza in poultry populations in Asia. This week, in a series of News Features and Commentary pieces, we cover the ground on one of the major health concerns of the day. Turn to page 399 for an overview, and to page 385 for editorial comment. The latest developments are covered in News, on pages 390 and 391.

negative: Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases PURPOSE: Infection with COVID-19 potentially can result in severe outcomes and death from “cytokine storm syndrome”, resulting in novel coronavirus pneumonia (NCP) with severe dyspnea, acute respiratory distress syndrome (ARDS), fulminant myocarditis and multiorgan dysfunction with or without disseminated intravascular coagulation. No published treatment to date has been shown to adequately control the inflammation and respiratory symptoms associated with COVID-19, apart from oxygen therapy and assisted ventilation. We evaluated the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients with dyspnea secondary to COVID-19 pneumonia. METHODS: Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms. CONCLUSION: Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing “cytokine storm syndrome” and respiratory distress in patients with COVID-19 pneumonia.

negative: Infectious diseases and governance of global risks through public communication and participation. In recent years a succession of health emergencies connected with the threat of new, possibly global, infectious diseases has stimulated the attention of the mass media, the scientific community, and international public opinion, setting a tough test for the institutions whose job is to manage the risks. On the basis of experience in the fields of AIDS, BSE, SARS and bird flu, this study discusses the strong and weak points of governance procedures for health risks. In particular, the paper illustrates how risk management can be improved by adopting practices and procedures which actively involve the public in dealing with the emergency, by taking a transparent and accessible approach to communication with the public (including the provision of information about the risks) and by fostering the unrestricted exchange of scientific knowledge among researchers. Lastly, the text shows how the analysis of these themes provides starting points for understanding the crisis in the current relationship between science and society.

negative: Exploring determinants of acceptance of the pandemic influenza A (H1N1) 2009 vaccination in nurses This study investigated the anticipated vaccination rate against pandemic human influenza A (H1N1) 2009 in the health care setting. Self-administered questionnaires were used to assess nurses' acceptance of vaccination against seasonal flu and H1N1. They were sent to nurses by post through various nurses' unions before initiation of the vaccination program. Only 13.3% of the respondents planned to receive the H1N1 vaccine, compared with 37.5% for the seasonal influenza vaccine. Vaccination against seasonal influenza in the preceding season strongly predicted the likelihood of H1N1 vaccination. The main reason cited for H1N1 vaccination was self-protection, and reasons for rejecting vaccination included possible side effects, ineffectiveness of the vaccine, and the mild nature of the disease. Personal contact with patients with H1N1 or severe acute respiratory syndrome at work did not significantly increase the likelihood of receiving the H1N1 vaccine. More than 40% of the respondents were undecided at the time of the survey. The promotion of vaccination against seasonal influenza may play a role in improving H1N1 vaccination coverage. Efforts are needed to address concerns about vaccination risk and to incorporate H1N1 vaccination in standard infection control practice with policy support.

negative: Evaluation of a Phylogenetic Marker Based on Genomic Segment B of Infectious Bursal Disease Virus: Facilitating a Feasible Incorporation of this Segment to the Molecular Epidemiology Studies for this Viral Agent BACKGROUND: Infectious bursal disease (IBD) is a highly contagious and acute viral disease, which has caused high mortality rates in birds and considerable economic losses in different parts of the world for more than two decades and it still represents a considerable threat to poultry. The current study was designed to rigorously measure the reliability of a phylogenetic marker included into segment B. This marker can facilitate molecular epidemiology studies, incorporating this segment of the viral genome, to better explain the links between emergence, spreading and maintenance of the very virulent IBD virus (vvIBDV) strains worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Sequences of the segment B gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank Database; Cuban sequences were obtained in the current work. A phylogenetic marker named B-marker was assessed by different phylogenetic principles such as saturation of substitution, phylogenetic noise and high consistency. This last parameter is based on the ability of B-marker to reconstruct the same topology as the complete segment B of the viral genome. From the results obtained from B-marker, demographic history for both main lineages of IBDV regarding segment B was performed by Bayesian skyline plot analysis. Phylogenetic analysis for both segments of IBDV genome was also performed, revealing the presence of a natural reassortant strain with segment A from vvIBDV strains and segment B from non-vvIBDV strains within Cuban IBDV population. CONCLUSIONS/SIGNIFICANCE: This study contributes to a better understanding of the emergence of vvIBDV strains, describing molecular epidemiology of IBDV using the state-of-the-art methodology concerning phylogenetic reconstruction. This study also revealed the presence of a novel natural reassorted strain as possible manifest of change in the genetic structure and stability of the vvIBDV strains. Therefore, it highlights the need to obtain information about both genome segments of IBDV for molecular epidemiology studies.

negative: The Novel Coronavirus Outbreak: What We Know and What We Don’t

negative: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19? INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. SUMMARY: Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.

negative: Inclusive Costs of NPI Measures for COVID-19 Pandemic: Three Approaches The paper evaluates total inclusive costs of three public health approaches to address the COVID-19 epidemic in the US based on epidemiological projections in Ferguson et al (2020). We calculate and add costs of lost productivity and costs of mortality measured through the value of statistical life. We find that the aggressive approach which involves strict suppression measures and a drastic reduction of economic activity for three months with extensive testing and case tracking afterwards results in the lowest total costs for the society. The approach of doing no non-pharmaceutical measures results in the lowest total costs if the infection fatality rate falls below 0.15%.

negative: Epidemiology and etiology of influenza-like-illness in households in Vietnam; it’s not all about the kids! BACKGROUND: Household studies provide opportunities to understand influenza-like-illness (ILI) transmission, but data from (sub)tropical developing countries are scarce. OBJECTIVE: To determine the viral etiology and epidemiology of ILI in households. STUDY DESIGN: ILI was detected by active case finding amongst a cohort of 263 northern Vietnam households between 2008 and 2013. Health workers collected nose and throat swabs for virus detection by multiplex real-time RT-PCR. RESULTS: ILI was detected at least once in 219 (23.7%) of 945 household members. 271 (62.3%) of 435 nose/throat swabs were positive for at least one of the 15 viruses tested. Six viruses predominated amongst positive swabs: Rhinovirus (28%), Influenza virus (17%), Coronavirus (8%), Enterovirus (5%), Respiratory syncytial virus (3%), Metapneumovirus virus (2.5%) and Parainfluenza virus 3 (1.8%). There was no clear seasonality, but 78% of episodes occurred in Winter/Spring for Influenza compared to 32% for Rhinovirus. Participants, on average, suffered 0.49 ILI, and 0.29 virus-positive ILI episodes, with no significant effects of gender, age, or household size. In contrast to US and Australian community studies, the frequency of ILI decreased as the number of household members aged below 5 years increased (p = 0.006). CONCLUSION: The findings indicate the need for tailored ILI control strategies, and for better understanding of how local childcare practices and seasonality may influence transmission and the role of children.

negative: Pan-human coronavirus and human bocavirus SYBR Green and TaqMan PCR assays; use in studying influenza A viruses co-infection and risk of hospitalization PURPOSE: Influenza A viruses, human coronaviruses (hCoV) and human bocavirus (hBoV) are emerging respiratory viruses. This study investigated the association between influenza A viruses co-infection with hBoV and hCoV and severity and the sensitivity of a real-time polymerase chain reaction (RT-PCR) assay for identification of 15 coronaviruses. METHODOLOGY: Published sequences for the 15 human coronaviruses were used to design a consensus PCR targeting the replicase open reading frame 1b. A previously published PCR targeting the NS1 Gene of all known human bocavirus strains was also utilized. A series of 217 samples from patients aged 37.7 (SD ± 30.4)] with seasonal influenza A viruses (SeasFluA) identified between 06/2011 and 06/2012 in NW England were tested for hCoV and hBoV using RT-PCR. Association between co-infection and disease outcome was assessed using logistic regression. RESULTS: The limit of detection of hCoV RT-PCR assay was 2 copies/µl of human coronavirus RNA template, a sensitivity comparable to a previously published SYBR green assay for human coronaviruses. A total of 12 hCoV and 17 hBoV were identified in the 217 influenza A positive samples. A higher proportion (61.5 %; 8/13) of SeasFluA/hBoV co-infections were identified in patients that were admitted either to a general ward or the intensive care unit compared to 44.3 % (66/149) of single SeasFlu A virus infections (OR 2.5 95 % CI 0.67–9.34, p = 0.17). In a stratified analysis, there was a trend towards higher association between FluA, hCoV and hBoV with increasing age (especially in patients aged 24–45 years and >65 year old). CONCLUSION: Our hCoV RT-PCR protocol appeared to be of adequate analytical sensitivity for diagnosis. More and larger studies are needed to confirm the role of hCoV, hBoV in causing severe disease when they co-infect with influenza A viruses.

negative: An editorial perspective on the infamous COVID-19 studies retracted by Lancet and NEJM.

negative: Similar virus spectra and seasonality in paediatric patients with acute respiratory disease, Ghana and Germany Abstract Epidemiological differences between tropical and temperate regions regarding viruses causing acute respiratory infection are poorly understood. This is in part because methodological differences limit the comparability of data from these two regions. Using identical molecular detection methods, we tested 1174 Ghanaian and 539 German children with acute respiratory infections sampled over 12 months for the 15 most common respiratory viruses by PCR. A total 43.2% of the Ghanaian and 56.6% of the German children tested positive for at least one respiratory virus. The pneumoviruses respiratory syncytial virus and human metapneumovirus were most frequently detected, in 13.1% and 25.1% within the Ghanaian and German children, respectively. At both study sites, pneumoviruses were more often observed at younger ages (p <0.001). In the Ghanaian rainy season, enveloped viruses were detected twice as often as non-enveloped viruses (prevalence rate ratio (PR) 2.0, 95% CI 1.7–2.4). In contrast, non-enveloped viruses were more frequent during the Ghanaian dry season (PR 0.6, 95% CI 0.4–0.8). In Germany, enveloped viruses were also more frequently detected during the relatively colder winter season (PR 1.6, 95% CI 1.2–2.1) and non-enveloped viruses during summer (PR 0.7, 95% CI 0.5–0.9). Despite a distance of about 5000 km and a difference of 44° latitude separating Germany and Ghana, virus spectra, age associations and seasonal fluctuation showed similarities between sites. Neither respiratory viruses overall, nor environmentally stable (non-enveloped) viruses in particular were more frequent in tropical Ghana. The standardization of our sampling and laboratory testing revealed similarities in acute respiratory infection virus patterns in tropical and temperate climates.

negative: Mutual Moral Obligations in the Prevention of Infectious Diseases Not so long ago health policy was about little more than the provision of medical care. The availability of treatment is important for those in need of cure, but by now it is a well-shown fact that health is generally determined to a much greater extent by other factors. Genetic constitution, lifestyle choices and socio-economic environment largely explain why some of us become ill or die earlier than others who remain healthy (Mackenbach 1996; McKeown 1976; Wilkinson and Marmot 2003). While some of these factors fall under the control of an individual, the majority does not. Research increasingly indicates how remarkably sensitive our health seems to be to what has become known as the ‘social determinants of health’. These factors generally fall beyond the control of an individual, but can nonetheless be influenced on a population level. This causes a shift in the focus of health policy from the classic provision of health care to policies specifically designed to influence the causal factors of ill-health in different non-medical fields. The flipside of that evolution is a significant increase of the state’s influence in the sphere of individual lives. A pertinent question remains the one that asks for the legitimate role of governments in modifying, discouraging or prohibiting behaviors that lead to ill-health. To what extent can and should we hold public policy responsible for us leading a healthy life? Most scholars will argue that governments indeed have a role to play, but that the limits will be reached when public health measures would imply large sacrifices of individual liberty.

negative: People at Risk of Influenza Pandemics: The Evolution of Perception and Behavior Influenza pandemics can severely impact human health and society. Understanding public perception and behavior toward influenza pandemics is important for minimizing the effects of such events. Public perception and behavior are expected to change over the course of an influenza pandemic, but this idea has received little attention in previous studies. Our study aimed to understand the dynamics of public perception and behavior over the course of the 2009 H1N1 influenza pandemic. Three consecutive cross-sectional surveys were administered among Beijing residents with random-digit dialing techniques in March 2008 and August and November 2009. Effective samples of 507, 508 and 1006 respondents were interviewed in each of the three surveys, respectively. The mean scores of risk perception were low to moderate across the three surveys. The perceived risk of infection of self was significantly lower than that of the community, revealing an optimistic bias. Longitudinally, the perceived risk of contracting H1N1 increased, whereas the perceived risk of being unable to obtain medicine and medical care once influenza permeated the community first increased and then decreased. Responsive actions toward influenza varied. Most respondents took actions that required little extra effort, such as ventilating rooms; these actions did not change over time. Comparatively, a smaller number of respondents took actions for coping with influenza, such as vaccination; however, these actions were taken by an increasing number of respondents over time. The association between risk perception and behavior was unstable. Positive, insignificant, and negative associations were obtained in the three surveys. In conclusion, the evolving patterns of risk perception and responsive behavior over the course of an influenza pandemic are sensitive to how risk and behavior are defined and scoped.

negative: A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world(1,2,3). A new coronavirus (SARS-CoV) was identified as the SARS pathogen(4,5,6,7), which triggered severe pneumonia and acute, often lethal, lung failure(8). Moreover, among infected individuals influenza such as the Spanish flu(9,10) and the emergence of new respiratory disease viruses(11,12) have caused high lethality resulting from acute lung failure(13). In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor(14). The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1267) contains supplementary material, which is available to authorized users.

negative: Differences in sources of information used by the population between the affected area and the general population during the first phase of a bird flu outbreak. INTRODUCTION In March 2006, a few cases of bird flu were discovered in approximately 10 rural settlements in Israel. As a result, approximately one million birds were destroyed within a three kilometer radius of the settlements. The Israeli population was instructed to take preventive measures against the spread of the infection. OBJECTIVES The objective of this study was to compare the frequency of use of different sources of information by the population in the affected area with the general population during the first phase of a bird flu outbreak in Israel. METHODS A telephone survey among two randomly selected, representative samples of adults was conducted. One sample involved 500 adult Israeli residents; the other sample involved 103 adult residents from the affected area during the first phase of the outbreak. The use of different sources of information by the population concerning the disease was assessed. The differences in these parameters between the affected area and the nationwide population were analyzed using a chi-square and t-test analysis. A p-value of < 0.05 was considered statistically significant. RESULTS Television was a significantly more common source of information in Israel as a whole (p < 0.05), whereas friends (p < 0.05) and local authorities (p < 0.05) were significantly more common sources of information in the affected area. CONCLUSIONS The frequency of use of the sources of information by the population during the early phase of a bird flu outbreak is different in the affected area compared with the general population in the same country. Authorities must pay attention to this phenomenon and use the correct sources of information in each area in order to achieve better exposure of the population to the recommended behaviors during an outbreak.

negative: Covid19 Surveillance in Peru on April using Text Mining The present outbreak as consequence by coronavirus covid19 has generated an big impact over the world. South American countries had their own limitations, challengues and pandemic has highlighted what needs to improve. Peru is a country with good start with quarantine, social distancing policies but the policies was not enough during the weeks. So, the analysis over April is performed through infoveillance using posts from different cities to analyze what population was living or worried during this month. Results presents a high concern about international context, and national situation, besides Economy and Politics are issues to solve. By constrast, Religion and Transport are not very important for peruvian citizens.

negative: Virome of New York Presbyterian Hospital pediatric emergency Background: Viral infection of the respiratory tract is one of the major causes of hospital visits for young children. In this study, we report the occurrence and co-occurrence of different virus types and subtypes among the patients arriving at the pediatric emergency room of New York Presbyterian Hospital, a major urban hospital. Methods: We collected nasal swabs from the patients and their accompanying persons. We also recorded the levels (None, Mild, High, and Severe) of their symptoms (Fever, Chill, Muscle Pain, Watery Eye, Runny Nose, Sneezing, Sore throat and Cough). The collected swabs were tested for the presence of common viruses infecting the respiratory tract. Results: Human Rhinovirus was the most common virus among the patients, followed Influenza and Respiratory Syncytial Virus. Human Rhinovirus was most common in summer, autumn and spring. In contrast, influenza was more common in winter. Further, Influenza A virus was more likely to co-occur with Corona Virus 229E. In comparison, Influenza was less likely to co-occur with Human Rhinovirus. Moreover, Influenza, Parainfluenza and Corona virus were associated with more severe symptoms, while Human Rhinovirus was associated with less severe symptoms. In addition, we observed that Influenza and Respiratory Syncytial Virus were more likely to infect a patient when these viruses also infected the accompanying person. We also found that it was difficult to distinguish among viruses based on the symptoms. The inability to distinguish among different virus types and subtypes is explained by the fact that multiple viruses lead to similar symptoms. Conclusions: The findings of this study provide a better understanding of respiratory viral infections in small children presenting at a pediatric emergency room in New York.

negative: Adult outpatient experience of the 2009 H1N1 pandemic: Clinical course, pathogens, and evaluation of case definitions Summary Objectives The aim was to describe causative agents and clinical characteristics in adult outpatients with upper airway symptoms during the 2009 H1N1 pandemic and to evaluate case definitions that are used in clinical practice. Methods From August through December 2009, 964 symptomatic adult outpatients were included. RT-PCR was used to detect the following pathogens: influenza A (H1N1) and B, parainfluenza 1–4, adenovirus, respiratory syncytial virus, human rhinovirus, human metapneumovirus, human coronavirus (OC43, 229E, NL63), Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella species. The Dutch GHOR, American CDC and WHO, and British HPA case definitions were evaluated. Results A respiratory pathogen was detected in 41% of tested patient samples; influenza A (H1N1) and human rhinovirus were both detected in 16%. Clinical presentation of influenza cases was significantly more serious when compared to rhinovirus or negative-tested cases. Test characteristics were almost similar for all 4 case definitions, with an average sensitivity of 66%, specificity of 70%, positive predictive value of 34% and negative predictive value of 90%. Conclusions Influenza A (H1N1) and human rhinovirus were the major pathogens responsible for respiratory disease. The 2009 H1N1 pandemic in Amsterdam followed a mild course. Test characteristics of 4 different clinical case definitions seemed comparable but rather useless.

negative: SARS vs. flu: can you tell serious disease from common malady? Health officials caution that severe acute respiratory syndrome (SARS) may return this fall with the flu season, and the serious disease may be difficult to distinguish from the common malady. Paying attention to public health trends will help you determine how much a diagnosing concern SARS should be in your own ED. More use of rapid diagnostic tests for flu may help, but don't depend too much on them. Confirming a flu diagnosis means you're relatively safe in ruling out SARS. ED physicians may have to be overly cautious this year in identifying cases of potential SARS.

negative: Neurological Impact of Coronavirus Disease (COVID-19): Practical Considerations for the Neuroscience Community Abstract Background The coronavirus disease of 2019 (COVID-19) that is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been designated a pandemic by the World Health Organization, affecting 2.7 million individuals globally as of April 25, 2020 with over 187,000 deaths. A growing body of evidence supports central nervous system (CNS) involvement. Methods We conducted a review of the literature for articles concerning COVID-19 pathophysiology, neurological manifestations, and neuroscience provider recommendations and guidelines. Results CNS manifestations range from vague non-focal complaints to severe neurologic impairment associated with encephalitis. It is unclear whether neurological dysfunction is due to direct viral injury or systemic disease. The virus may affect brainstem pathways that lead to indirect respiratory dysfunction in addition to direct pulmonary injury. Necessary adaptations in patient management, triage, and diagnosis are evolving in light of ongoing scientific and clinical findings. Conclusions This review consolidates the current body of literature regarding the neurological impact of coronaviruses, discusses the reported neurologic manifestations of COVID-19, and highlights recommendations for patient management. Specific recommendations pertaining to clinical practice for neurologists and neurosurgeons are provided.

negative: ELM—the database of eukaryotic linear motifs Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.

negative: Influenza treatment with neuraminidase inhibitors: Cost-effectiveness and cost-utility in healthy adults in the United Kingdom We assessed the cost-effectiveness and cost-utility of treating influenza with neuraminidase inhibitors (oseltamivir and zanamivir) from a health care payer’s and societal perspective in the United Kingdom. A simulation model was developed to predict morbidity and mortality due to influenza and its specified complications, comparing neuraminidase inhibitors with usual care in an otherwise healthy adult population. Robustness of the results was tested by one-way and multiway as well as probabilistic sensitivity analyses. Treatment with either neuraminidase inhibitor results in reduced morbidity and faster return to normal activities. However, oseltamivir dominates zanamivir in cost-utility analysis due to its lower costs. Comparing oseltamivir with usual care, the costs are £14.36 per day of normal activity gained and £5,600 per quality-adjusted life-year gained from the healthcare payer perspective. Oseltamivir dominates usual care from the societal perspective. Treatment with oseltamivir is a cost-effective strategy for otherwise healthy adults in the UK from both the healthcare payer and societal perspective.

negative: What Can We Estimate from Fatality and Infectious Case Data using the Susceptible-Infected-Removed (SIR) model? A case Study of Covid-19 Pandemic The rapidly spreading Covid-19 that affected almost all countries, was first reported at the end of 2019. As a consequence of its highly infectious nature, countries all over the world have imposed extremely strict measures to control its spread. Since the earliest stages of this major pandemic, academics have done a huge amount of research in order to understand the disease, develop medication, vaccines and tests, and model its spread. Among these studies, a great deal of effort has been invested in the estimation of epidemic parameters in the early stage, for the countries affected by Covid-19, hence to predict the course of the epidemic but the variability of the controls over the course of the epidemic complicated the modeling processes. In this article, the determination of the basic reproduction number, the mean duration of the infectious period, the estimation of the timing of the peak of the epidemic wave is discussed using early phase data. Daily case reports and daily fatalities for ten countries over the period January 22, 2020 - April 18, 2020 are evaluated using the Susceptible-Infected-Removed (SIR) model. For each country, the SIR models fitting cumulative infective case data within 5% error are analysed. It is observed that the basic reproduction number and the mean duration of the infectious period can be estimated only in cases where the spread of the epidemic is over (for China and South Korea in the present case). Nevertheless, it is shown that the timing of the maximum and timings of the inflection points of the proportion of infected individuals can be robustly estimated from the normalized data. The validation of the estimates by comparing the predictions with actual data has shown that the predictions were realised for all countries except USA, as long as lock-down measures were retained.

negative: Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation The outbreak of a novel betacoronavirus (2019-nCov) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for urgently needed vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development we determined a 3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. The atomic-resolution structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.

negative: Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea BACKGROUND: Community–acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0–18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2–18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.

negative: Preferences for scarce medical resource allocation: Differences between experts and the general public and implications for the COVID‐19 pandemic This study concerns what lay people believe is the best way to allocate scarce medical resources. A sample of 515 individuals completed a short questionnaire asking them to rank‐order eight different ethical positions with respect to the allocation of scarce resources. They showed a strong preference for the ‘saves most lives’ and ‘sickest first’ options, with ‘reciprocity’ and a ‘lottery’ being least favoured. There was a reasonable degree of unanimity amongst respondents and comparatively few correlations with individual difference factors such as demography. The preference results are compared to expert recommendations (Emanuel et al., 2020, N. Engl. J. Med., 382, 2049) made in light of the current coronavirus pandemic, and differences are highlighted. Implications for scare medical resource allocations are discussed, and limitations of the study acknowledged.

negative: Clinical Impact of Human Coronaviruses 229E and OC43 Infection in Diverse Adult Populations Background. The incidence and clinical impact of coronavirus (CoV) infection in elderly persons and those with underlying cardiopulmonary disease over a long duration is not well described. We determined the incidence and clinical impact of 229E and OC43 CoV in this population during 4 consecutive winters, and compared illnesses to influenza A, respiratory syncytial virus, and human metapneumovirus. Methods. CoV 229E and OC43 were detected by reverse transcription polymerase chain reaction and serology in 4 adult populations under surveillance for acute respiratory illness during the winters of 1999–2003. Cohorts included healthy young adults, healthy elderly adults, high-risk adults with underlying cardiopulmonary disease, and a hospitalized group. Results. Three hundred ninety-eight CoV infections were identified, with annual infection rates ranging from 2.8% to 26% in prospective cohorts, and prevalence ranging from 3.3% to 11.1% in the hospitalized cohort. The incidence of infections with each strain was similar, although asymptomatic infection and viral coinfection was significantly more common with 229E than OC43 infection. Although the incidence and clinical manifestations were similar for each strain, OC43-infected subjects tended to seek more medical care, as OC43 was twice as common as 229E among the hospitalized cohort. Conclusions. CoV infections in the elderly are frequent, likely causing substantial medical disease burden.

negative: Cross‐species transmission of the newly identified coronavirus 2019‐nCoV The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.

negative: Transmission characteristics of the COVID-19 outbreak in China: a study driven by data The COVID-19 outbreak has been a serious public health threat worldwide. We use individually documented case descriptions of COVID-19 from China (excluding Hubei Province) to estimate the distributions of the generation time, incubation period, and periods from symptom onset to isolation and to diagnosis. The recommended 14-day quarantine period may lead to a 6.7% failure for quarantine. We recommend a 22-day quarantine period. The mean generation time is 3.3 days and the mean incubation period is 7.2 days. It took 3.7 days to isolate and 6.6 days to diagnose a patient after his/her symptom onset. Patients may become infectious on average 3.9 days before showing major symptoms. This makes contact tracing and quarantine ineffective. The basic reproduction number is estimated to be 1.54 with contact tracing, quarantine and isolation, mostly driven by super spreaders.

negative: Seasonal Influenza Vaccine Impact on Pandemic H1N1 Vaccine Efficacy BACKGROUND: In 2009, a novel influenza A (pH1N1) was identified, resulting in a pandemic with significant morbidity and mortality. A monovalent pH1N1 vaccine was separately produced in addition to the seasonal trivalent influenza vaccine. Formulation of the seasonal influenza vaccine (injectable trivalent inactivated influenza vaccine [TIV] vs. intranasal live, attenuated influenza vaccine [LAIV]) was postulated to have impacted the efficacy of the pH1N1 vaccination. METHODS: We reviewed electronic health and databases, which included vaccination records, and healthcare encounters for influenza-like illness (ILI), influenza, and pneumonia among US military members. We examined rates by vaccination type to identify factors associated with the risk for study outcomes. RESULTS: Compared with those receiving the seasonal influenza vaccine alone, subjects receiving the pH1N1 vaccine, either alone (RR, 0.49) or in addition to the seasonal vaccine (RR, 0.51), had an approximately 50% reduction in ILI, 88% reduction in influenza (RR, 0.11 and 0.12, respectively), and 63% reduction in pneumonia (RR, 0.37 and 0.35, respectively). There was no clinically significant difference in ILI, influenza, or pneumonia attack rates among those receiving the pH1N1 vaccine with or without presence of the seasonal vaccine. Similarly, there was no clinically relevant difference in pH1N1 effectiveness between seasonal TIV and LAIV recipients. CONCLUSIONS: During the 2009–2010 pandemic, the pH1N1 vaccination was effective in reducing rates of ILI, influenza, and pneumonia. Administration of the seasonal vaccine should continue without concern of potential interference with a novel pandemic vaccine, though more studies are needed to determine if this is applicable to other influenza seasons.

negative: US withdrawal from WHO is unlawful and threatens global and US health and security

negative: Clinical significance of IgM and IgG test for diagnosis of highly suspected COVID-19 infection Quick, simple and accurate diagnosis of suspected COVID-19 is very important for the screening and therapy of patients. Although several methods were performed in clinical practice, however, the IgM and IgG diagnostic value evaluation was little performed. 57 suspected COVID-19 infection patients were enrolled in our study. 24 patients with positive and 33 patients with negative nucleic acid test. The positive rate of COVID-19 nucleic acid was 42.10%. The positive detection rate of combination of IgM and IgG for patients with COVID-19 negative and positive nucleic acid test was 72.73% and 87.50%. The results were significantly higher than the nucleic acid or IgM, IgG single detection. hsCRP in the COVID-19 nucleic acid negative group showed significantly higher than the positive groups (P=0.0298). AST in the COVID-19 IgM negative group showed significantly lower than the positive groups (P=0.0365). We suggest a quick, simple, accurate aided detection method for the suspected patients and on-site screening in close contact with the population.

negative: Competition between Influenza A Virus Genome Segments Influenza A virus (IAV) contains a segmented negative-strand RNA genome. How IAV balances the replication and transcription of its multiple genome segments is not understood. We developed a dual competition assay based on the co-transfection of firefly or Gaussia luciferase-encoding genome segments together with plasmids encoding IAV polymerase subunits and nucleoprotein. At limiting amounts of polymerase subunits, expression of the firefly luciferase segment was negatively affected by the presence of its Gaussia luciferase counterpart, indicative of competition between reporter genome segments. This competition could be relieved by increasing or decreasing the relative amounts of firefly or Gaussia reporter segment, respectively. The balance between the luciferase expression levels was also affected by the identity of the untranslated regions (UTRs) as well as segment length. In general it appeared that genome segments displaying inherent higher expression levels were more efficient competitors of another segment. When natural genome segments were tested for their ability to suppress reporter gene expression, shorter genome segments generally reduced firefly luciferase expression to a larger extent, with the M and NS segments having the largest effect. The balance between different reporter segments was most dramatically affected by the introduction of UTR panhandle-stabilizing mutations. Furthermore, only reporter genome segments carrying these mutations were able to efficiently compete with the natural genome segments in infected cells. Our data indicate that IAV genome segments compete for available polymerases. Competition is affected by segment length, coding region, and UTRs. This competition is probably most apparent early during infection, when limiting amounts of polymerases are present, and may contribute to the regulation of segment-specific replication and transcription.

negative: COVID-19: Important Therapy Considerations and Approaches in this Hour of Need

negative: A fast and simple one-step duplex PCR assay for canine distemper virus (CDV) and canine coronavirus (CCoV) detection The one-step polymerase chain reaction (one-step PCR) detection assay is an innovative PCR detection method, eliminating nucleic acid extraction steps, in which samples can be directly added to PCR reagents for testing. For simultaneous detection of CDV and CCoV, a sensitive and specific one-step duplex PCR (one-step dPCR) assay was developed with two pairs of primers that were designed based on H and M gene sequences of CDV and CCoV, respectively. The one-step dPCR with optimized detection conditions has high specificity and sensitivity; independent sequencing assays further verified these results.

negative: Are the COVID19 restrictions really worth the cost? A comparison of estimated mortality in Australia from COVID19 and economic recession There has been considerable public debate about whether the economic impact of the current COVID19 restrictions are worth the costs. Although the potential impact of COVID19 has been modelled extensively, very few numbers have been presented in the discussions about potential economic impacts. For a good answer to the question - will the restrictions cause as much harm as COVID19? - credible evidence-based estimates are required, rather than simply rhetoric. Here we provide some preliminary estimates to compare the impact of the current restrictions against the direct impact of the virus. Since most countries are currently taking an approach that reduces the number of COVID19 deaths, the estimates we provide for deaths from COVID19 are deliberately taken from the low end of the estimates of the infection fatality rate, while estimates for deaths from an economic recession are deliberately computed from double the high end of confidence interval for severe economic recessions. This ensures that an adequate challenge to the status quo of the current restrictions is provided. Our analysis shows that strict restrictions to eradicate the virus are likely to lead to at least eight times fewer total deaths than an immediate return to work scenario.

negative: Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries Abstract The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 °C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.

negative: Human coronavirus OC43 and other respiratory viruses from acute respiratory infections of Egyptian children. Respiratory infections have a significant impact on health worldwide. Viruses are major causes of acute respiratory infections among children. Limited information regarding its prevalence in Egypt is available. This study investigated prevalence of 10 respiratory viruses; Adenovirus, influenza A, B, respiratory syncytial virus (RSV), Parainfluenza virus (PIV)type 1-4, enterovirus, and human coronavirus OC43 (HCoV-OC43) among children in Alexandria, Egypt presenting with acute lower respiratory tract infections. The study was conducted on children <14 years of age selected from ElShatby Pediatric Hospital, Alexandria University, Egypt. One hundred children presenting during winter season with influenza-like illness were eligible for the study. Oropharyngeal swabs were collected and subjected to viral RNA and DNA extraction followed by polymerase chain reaction. Viral infections were detected in 44% of cases. Adenovirus was the most common, it was found in 19% of the patients. Prevalence of PIV (3 and 4) and enterovirus was 7% each. Prevalence of RSV and HCoV-OC43 was 5% and 3% respectively. Two percentage were Influenza A positive and 1% positive for influenza B. Mixed viral infection was observed in 7%. To the best of our knowledge, this is the first report of the isolation of HCoV-OC43 from respiratory infections in Alexandria, Egypt.

negative: Global health concerns stirred by emerging viral infections Emerging viral infections continue to pose a major threat to global public health. In 1997, a highly pathogenic avian influenza A (H5N1) virus was found to directly spread from poultry to humans unlike previously reported transmission routs of human-to-human and livestock-to-human, stirring a grave concern for a possible influenza pandemic. This article is protected by copyright. All rights reserved.

negative: The Role of Sociodemographic and Psychological Variables on Risk Perception of the Flu Influenza is a source of mortality and morbidity, and vigilance of health authorities for flu viruses is high. The World Health Organization (WHO) highlighted that the first lines of defense against infectious diseases are behavioral, and risk perception affects behavioral measures. This study investigated risk perception of influenza and the role of sociodemographic and psychological variables on perceived risk. Participants were 442 adults. The research was conducted using three measures: an adjustment of the “Risk Perception of Infectious Disease Questionnaire,” the “General Self-Efficacy Scale,” and the short form of the “Italian Personality Inventory.” The results showed that age, education, self-efficacy, and personality influenced risk perception. The evidence that sociodemographic and psychological factors contribute to risk perception of a disease shows the need to take into account these variables in the planning of informative campaigns, with the aim to achieve favorable changes in public behavior. These issues might have implications for the ameliorating health communication efforts and successful response to new influenza outbreaks.

negative: Influenza A non-H1N1 associated with acute respiratory failure and acute renal failure in a previously vaccinated cystic fibrosis patient In the 2014 - 2015 season, most influenza infections were due to A (H3N2) viruses. More than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014 - 2015 northern and southern Hemisphere seasonal influenza vaccines. The purpose of this paper is to report a case of seasonal influenza A non-H1N1 infection that occurred in June 2015 in an adult cystic fibrosis patient with severe lung disease previously vaccinated with the anti-flu trivalent vaccine. The patient evolved to respiratory and renal failure (without rhabdomyolysis) and was placed under mechanical ventilation and hemodialysis. The clinical outcome was positive after 39 days of hospital stay. In addition, the patient was clinically stable after 18 months of follow-up. With the recent advances in critical care medicine and in cystic fibrosis treatment, survival with advanced pulmonary disease in cystic fibrosis presents new questions and potential problems, which are still being formulated.

negative: Survey on the Likely Behavioural Changes of the General Public in Four European Countries During the 2009/2010 Pandemic In order to assess the likely impact of public health interventions, it is important to predict the acceptance of control measures, as well as the behavioural changes that may occur among the general public in response to epidemics, in particular lethal ones. The emergence of 2009 pandemic allowed us to assess the general public’s behaviour during the pandemic, via two surveys: one at the beginning and one after the first wave of the 2009 pandemic, in four European countries.Results showed some differences between participating countries in previous behaviours relating to seasonal flu and in beliefs and knowledge about 2009 pandemic influenza. No substantial differences were detected among the four countries in the first survey with respect to the intended behaviours in anticipation of the spread of the pandemic virus. However, results from the second survey showed differences within and among the four participating countries. The two surveys were useful in showing differences between behavioural intentions and actual actions related to the 2009 pandemic influenza. To our knowledge this is the first study investigating the actual behaviour of the population in four EU countries and provides crucial descriptions of pandemic impact on social-network dynamics parameters which can be included in mathematical models.

negative: An update on swine-origin influenza virus A/H1N1: a review Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. The recent flu pandemic caused by a swine-origin influenza virus A/H1N1 (S-OIV) presents an opportunity to examine virulence factors, the spread of the infection and to prepare for major influenza outbreaks in the future. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it probably arose through reassortment of two viruses of swine origin. Specific markers for virulence can be evaluated in the viral genome, PB1-F2 is a molecular marker of pathogenicity but is not present in the new S-OIV. While attention was focused on a threat of an avian influenza H5N1 pandemic emerging from Asia, a novel influenza virus of swine origin emerged in North America, and is now spreading worldwide. However, S-OIV demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. There are concerns that this virus may mutate or reassort with existing influenza viruses giving rise to more transmissible or more pathogenic viruses. The 1918 Spanish flu pandemic virus was relatively mild in its first wave and acquired more virulence when it returned in the winter. Thus preparedness on a global scale against a potential more virulent strain is highly recommended. Most isolates of the new S-OIVs are susceptible to neuraminidase inhibitors, and currently a vaccine against the pandemic strain is being manufactured and will be available this fall. This review summarizes the current information on the new pandemic swine-origin influenza virus A/H1N1.

negative: Immuno-epidemiological model of two-stage epidemic growth Epidemiological data on seasonal influenza show that the growth rate of the number of infected individuals can increase passing from one exponential growth rate to another one with a larger exponent. Such behavior is not described by conventional epidemiological models. In this work an immuno-epidemiological model is proposed in order to describe this two-stage growth. It takes into account that the growth in the number of infected individuals increases the initial viral load and provides a passage from the first stage of epidemic where only people with weak immune response are infected to the second stage where people with strong immune response are also infected. This scenario may be viewed as an increase of the effective number of susceptible increasing the effective growth rate of infected.

negative: Immune-epidemiological parameters of the novel coronavirus – a perspective Introduction: At the end of 2019, Wuhan, a city in China with a population of about 11 million, witnessed the outbreak of unusual pneumonia. As of 29 March 2020, the disease has spread to more 199 countries and territories worldwide. The 2019 novel coronavirus, 2019-nCoV, is known as the probable causative agent of the illness. Areas covered: Here, the epidemiological dynamics of the coronavirus disease 2019 (COVID-19) that stand in close relation to distinct immunogenetic characters of the pathogen are discussed, to understand the ability and inability of the immune system in combatting COVID-19. Expert opinion: The elderly population is at increased risk of developing and dying from COVID-19. Comorbidity is present in more than 30% of cases with COVID-19. Except for less than 1% of the total, a chronic condition has been found in all cases that died from COVID-19. Men are more than 1.5 times more likely to die from COVID-19. Evidence links aging to cytokine dysregulation and T-cell repertoire reduction, male population to relatively reduced anti-viral immunity, and COVID-19-related comorbidities to hyper inflammation. The transmission of COVID-19 is influenced by the host-related factors that are known to be associated with immune dysregulation.

negative: Porcine Epidemic Diarrhea Virus 3C-Like Protease Regulates Its Interferon Antagonism by Cleaving NEMO. UNLABELLED Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus causing lethal watery diarrhea in piglets. Since 2010, a PEDV variant has spread rapidly in China, and it emerged in the United States in 2013, posing significant economic and public health concerns. The ability to circumvent the interferon (IFN) antiviral response, as suggested for PEDV, promotes viral survival and regulates pathogenesis of PEDV infections, but the underlying mechanisms remain obscure. Here, we show that PEDV-encoded 3C-like protease, nsp5, is an IFN antagonist that proteolytically cleaves the nuclear transcription factor kappa B (NF-κB) essential modulator (NEMO), an essential adaptor bridging interferon-regulatory factor and NF-κB activation. NEMO is cleaved at glutamine 231 (Q231) by PEDV, and this cleavage impaired the ability of NEMO to activate downstream IFN production and to act as a signaling adaptor of the RIG-I/MDA5 pathway. Mutations specifically disrupting the cysteine protease activity of PEDV nsp5 abrogated NEMO cleavage and the inhibition of IFN induction. Structural analysis suggests that several key residues outside the catalytic sites of PEDV nsp5 probably impact NEMO cleavage by modulating potential interactions of nsp5 with their substrates. These data show that PEDV nsp5 disrupts type I IFN signaling by cleaving NEMO. Previously, we and others demonstrated that NEMO is also cleaved by 3C or 3C-like proteinases of picornavirus and artertivirus. Thus, NEMO probably represents a prime target for 3C or 3C-like proteinases of different viruses. IMPORTANCE The continued emergence and reemergence of porcine epidemic diarrhea virus (PEDV) underscore the importance of studying how this virus manipulates the immune responses of its hosts. During coevolution with its hosts, PEDV has acquired mechanisms to subvert host innate immune responses for its survival advantage. At least two proteins encoded by PEDV have been identified as interferon (IFN) antagonists, papain-like protease (PLP) and N protein. Here, we report that the PEDV nsp5 gene, which encodes the 3C-like protease of PEDV, is another IFN antagonist. Mechanistically, the cysteine protease activity of PEDV nsp5 mediates proteolysis of NEMO, the key adaptor for IFN synthesis, and NEMO is cleaved at glutamine 231 (Q231). The new molecular details and determinants impacting NEMO scission by PEDV nsp5 delineated in this study are fundamental to our understanding of critical virus-host interactions that determine PEDV pathogenesis.

negative: Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function (“dysbiosis”) in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.

negative: Analytical performance of the Alere™ i Influenza A&B assay for the rapid detection of influenza viruses The analytical performance of the new Alere™ i Influenza A&B kit (AL-Flu) assay, based on isothermal nucleic acids amplification, was evaluated and compared with an antigen detection method, SD Bioline Influenza Virus Antigen Test (SDB), and an automated real-time RT-PCR, Simplexa™ Flu A/B & VRS Direct assay (SPX), for detection of influenza viruses. An “in-house” RT-PCR was used as the reference method. Sensitivity of AL-Flu, SDB, and SPX was 71.7%, 34.8%, and 100%, respectively. Specificity was 100% for all techniques. The turnaround time was 13 min for AL-Flu, 15 min for SDB, and 75 min for SPX. The Alere™ i Influenza A&B assay is an optimal point-of-care assay for influenza diagnosis in clinical emergency settings, and is more sensitive and specific than antigen detection methods.

negative: CHAPTER 4 Keeping Track of Viruses Publisher Summary This chapter introduces basic concepts of virology and exemplifies the usage of current technology for identifying and tracking viral pathogens. Virus structure, lifestyle, replication strategies, classication, the varied modes of transmission, infection, and disease manifestations are focussed upon in the chapter. Viruses are extremely simple “life” forms without metabolic capacity, organelles, translational machinery, or autonomous replicative potential; the essential elements of a virus are consequently minimal. A virus enters the host through any opportunistic opening of the body—; such as minute breaks in the skin barrier or mucosal linings of the eye, nose, etc. Antibodies produced during an infection often have the ability to bind the virus and reduce infectivity. An immediate question to solve during a virus outbreak is the mechanism by which the virus spreads. Viruses frequently infect animal or insect vectors that serve to pass the virus to humans. By identifying the virus through sequence analysis, a hypothetical reservoir can be predicted by the placement of the sequence on the phylogenetic tree‥ The varied modes of transmission, infection, and disease manifestations as they relate to the different diagnostic methods for virus identification are highlighted. Examples of naturally emerging viruses; such as Sin Nombre, Nipah, West Nile conclude the chapter. New technologies that allow the creation of manmade or “engineered” viruses, new frontiers in viral diagnostics, and a few thoughts on the future of virology are also presented. The global eradication of smallpox ranks as one of humankind's greatest accomplishments yet many viral challenges remain. HIV, hepatitis B and C, influenza, dengue, rotavirus, and many other viral diseases continue to affect tens of millions.

negative: Changing virulence of the SARS virus: the epidemiological evidence.

negative: SARS‐CoV‐2 coinfections: Could influenza and the common cold be beneficial? The novel coronavirus SARS‐CoV‐2 has rapidly spread around the world, causing serious illness and death and creating a heavy burden on the health care systems of many countries. Since the virus first emerged in late November 2019, its spread has coincided with peak circulation of several seasonal respiratory viruses, yet some studies have noted limited coinfections between SARS‐CoV‐2 and other viruses. We use a mathematical model of viral coinfection to study SARS‐CoV‐2 coinfections, finding that SARS‐CoV‐2 replication is easily suppressed by many common respiratory viruses. According to our model, this suppression is because SARS‐CoV‐2 has a lower growth rate (1.8 /d) than the other viruses examined in this study. The suppression of SARS‐CoV‐2 by other pathogens could have implications for the timing and severity of a second wave. This article is protected by copyright. All rights reserved.

negative: Trends in global warming and evolution of matrix protein 2 family from influenza A virus The global warming is an important factor affecting the biological evolution, and the influenza is an important disease that threatens humans with possible epidemics or pandemics. In this study, we attempted to analyze the trends in global warming and evolution of matrix protein 2 family from influenza A virus, because this protein is a target of anti-flu drug, and its mutation would have significant effect on the resistance to anti-flu drugs. The evolution of matrix protein 2 of influenza A virus from 1959 to 2008 was defined using the unpredictable portion of amino-acid pair predictability. Then the trend in this evolution was compared with the trend in the global temperature, the temperature in north and south hemispheres, and the temperature in influenza A virus sampling site, and species carrying influenza A virus. The results showed the similar trends in global warming and in evolution of M2 proteins although we could not correlate them at this stage of study. The study suggested the potential impact of global warming on the evolution of proteins from influenza A virus.

negative: Mutated COVID-19 may foretell a great risk for mankind in the future Coronavirus disease 2019 SARS-CoV-2 (COVID-19) is a zoonotic virus causing a variety of severe respiratory diseases. SARS-CoV-2 is closest to SARS-CoV and MERS-CoV in structure. The high prevalence of COVID-19 is a result of a lack of symptoms at onset. Our study aimed to present an overview of the virus in terms of structure, epidemiology, symptoms, treatment and prevention. Whole genome sequences and some viral proteins were investigated to determine gaps and changes in alternation of nucleotides and amino acid sequences. We evaluate 11 complete genome sequences of different coronaviruses using BAST and MAFFT software. We also selected seven types of structural proteins. We conclude that COVID-19 might produce new mutations, specifically in glycoproteins, so caution and complete preparation by health authorities is required.

negative: Analytical performance of the automated multianalyte point-of-care mariPOC® for the detection of respiratory viruses Abstract The analytical performance of mariPOC® respi test (ArcDia® Laboratories, Turku, Finland) was evaluated using nucleic acid amplification techniques (NAATs) as the gold standard. The mariPOC assay allows automated detection of antigens from 8 respiratory viruses: influenza A and B viruses, respiratory syncytial virus, adenovirus, human metapneumovirus, and parainfluenza viruses 1–3. Positive results from samples with high viral load are available in 20min. Nasopharyngeal aspirates (n=192) from patients with acute respiratory infection and from previously positive samples were analyzed by mariPOC and NAATs (SimplexaTM FluA/FluB & RSV kit [n=118] and Luminex® Respiratory virus panel xTAG® RVP FAST [n=74]). Sensitivity, specificity, positive predictive value, and negative predictive value of mariPOC were 85.4%, 99.2%, 95.9%, and 97%, respectively, and 84.6% of positive results were reported in 20min. The good analytical performance and extended portfolio of mariPOC show this rapid assay as a good alternative for the etiological diagnosis of acute respiratory infection in laboratories that are not equipped with molecular assays.

negative: The Effectiveness of Social Distancing in Mitigating COVID-19 Spread: a modelling analysis Background The novel coronavirus COVID19 has been classified by the World Health Organisation as a pandemic due to its worldwide spread. The ability of countries to contain and control transmission is critical in the absence of a vaccine. We evaluated a range of social distancing measures to determine which strategies are most effective in reducing the peak daily infection rate, and consequential pressure on the health care system. Methods Using COVID19 transmission data from the outbreak source in Hubei Province, China, collected prior to activation of containment measures, we adapted an established individual based simulation model of the city of Newcastle, Australia, population 272,409. Simulation of virus transmission in this community model without interventions provided a baseline from which to compare alternative social distancing strategies. The infection history of each individual was determined, as was the time infected. From this model generated data, the rate of growth in cases, the magnitude of the epidemic peak, and the outbreak duration were obtained. Findings The application of all four social distancing interventions: school closure, workplace non-attendance, increased case isolation, and community contact reduction is highly effective in flattening the epidemic curve, reducing the maximum daily case numbers, and lengthening outbreak duration. These were also found to be effective even after 10 weeks delay from index case arrivals. The most effective single intervention was found to be increasing case isolation, to 100 percent of children and 90 percent of adults. Interpretation As strong social distancing intervention strategies had the most effect in reducing the epidemic peak, this strategy may be considered when weaker strategies are first tried and found to be less effective. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society. Tradeoffs may need to be made between the effectiveness of social distancing strategies and population willingness to adhere to them.

negative: The Possible of Immunotherapy for COVID-19: a Systematic Review The novel coronavirus (2019-nCoV) is an emerging pathogen that was first described in late December 2019 and causes a severe respiratory infection in humans. Since the outbreak of COVID-19, international attention has raised to develop treatment and control options such as types of immunotherapies. The immunotherapy is an effective method for fighting against similar viral infections such as SARS-CoV, and MERS-CoV. These methods include several types of vaccines, monoclonal antibody candidates, and etc. This systematic review article was designed to evaluate the existing evidence and experience related to immunotherapy for 2019-nCoV. Web of Science (ISI), PubMed, and Scopus databases were used to search for suitable keywords such as 2019-nCoV, novel coronavirus, Immunotherapy, interleukin, vaccine and the related words for relevant publications up to 24.3.2020. The present systematic review was performed based on PRISMA protocol. Data extraction and quality valuation of articles were performed by two reviewers. 51 articles were the results of the search and based on the inclusions and exclusions criteria, 7 articles were included in the final review. As a conclusion of these studies demonstrated that although no serious research has been done on this subject at the time of writing this article, similar studies on the related viruses showed notable results. So immunotherapy for this virus can also be a suitable option.

negative: Characterization and mutational analysis of haemagglutinin and neuraminidase of H3N2 and H1N1pdm09 human influenza A viruses in Egypt Seasonal influenza viruses constitute a major global concern. Currently, H3N2 and H1N1pdm09 are the commonly circulating influenza A viruses. The haemagglutin and neuraminidase genes of influenza A(H3N2) and A(H1N1)pdm09 viruses from Egyptian paediatric patients with respiratory distress were sequenced. Mutational analysis of all published sequences from Egypt was evolutionary tracked for both HA and NA genes. Phylogenetic analysis of H3N2 HA showed that the Egyptian strains belong to 3C2 subclade while Egyptian A(H1N1)pdm09 strains belong to 6B1 subclade. Some Egyptian A(H1N1)pdm09, 2013–2014, strains form a new subclade; 6B3. High score of mutations were recorded in HA of H1N1pdm09 but higher was recorded in H3N2 strains. These findings confirmed a high mutation rate of influenza A subtypes specially H3N2 strains.

negative: Trends in influenza vaccination coverage in Portugal from 1998 to 2010: effect of major pandemic threats BACKGROUND: Vaccination is the key measure available for prevention of the public health burden of annual influenza epidemics. This article describes national trends in seasonal influenza vaccine (IV) coverage in Portugal from 1998/99 to 2010/11, analyzes progress towards meeting WHO 2010 coverage goals, and addresses the effect of major public health threats of the last 12 years (SARS in 2003/04, influenza A (H5N1) in 2005/06, and the influenza A (H1N1)2009 pandemic) on vaccination trends. METHODS: The National Institute of Health surveyed (12 times) a random sample of Portuguese families. IV coverage was estimated and was adjusted for age distribution and country region. Independence of age and sex coverage distribution was tested using a modified F-statistic with a 5% significance level. The effect of SARS, A (H5N1), and the A (H1N1)2009 pandemic was tested using a meta-regression model. The model was adjusted for IV coverage in the general population and in the age groups. RESULTS: Between 1998/99 and 2010/11 IV, coverage in the general population varied between 14.2% (CI (95%): 11.6%–16.8%) and 17.5% (CI (95%): 17.6%–21.6%). There was no trend in coverage (p = 0.097). In the younger age group (<15 years) a declining trend was identified until 2008/09 (p = 0.005). This trend reversed in 2009/10. There was also a gradual and significant increase in seasonal IV coverage in the elderly (p for trend < 0.001). After 2006/07, IV coverage remained near 50%. Adjusting for baseline trends, there was significantly higher coverage in the general population in 2003/04 (p = 0.032) and 2005/06 (p = 0.018). The high coverage observed in the <15-year age group in season 2009/10 was also significant (p = 0.015). CONCLUSIONS: IV coverage in the elderly population displayed an increasing trend, but the 75% WHO 2010 target was not met. This result indicates that influenza vaccination strategy should be improved to meet the ambitious WHO coverage goals. The major pandemic threats of the past decade had a modest but significant effect on seasonal influenza vaccination. There was an increase in vaccine uptake proportion in the general population in 2003/04 and in 2005/06, and in individuals <15 years old in 2009/10.

negative: Estimating required lockdown cycles before immunity to SARS-CoV-2: Model-based analyses of susceptible population sizes, S0, in seven European countries including the UK and Ireland Background: Following stringent social distancing measures, some European countries are beginning to report a slowed or negative rate of growth of daily case numbers testing positive for the novel coronavirus. The notion that the first wave of infection is close to its peak begs the question of whether future peaks or second waves are likely. We sought to determine the current size of the effective (i.e. susceptible) population for seven European countries - to estimate immunity levels following this first wave. We compare these numbers to the total population sizes of these countries, in order to investigate the potential for future peaks. Methods: We used Bayesian model inversion to estimate epidemic parameters from the reported case and death rates from seven countries using data from late January 2020 to April 5th 2020. Two distinct generative model types were employed: first a continuous time dynamical-systems implementation of a Susceptible-Exposed-Infectious-Recovered (SEIR) model and second: a partially observable Markov Decision Process (MDP) or hidden Markov model (HMM) implementation of an SEIR model. Both models parameterise the size of the initial susceptible population (S0), as well as epidemic parameters. Parameter estimation (data fitting) was performed using a standard Bayesian scheme (variational Laplace) designed to allow for latent unobservable states and uncertainty in model parameters. Results: Both models recapitulated the dynamics of transmissions and disease as given by case and death rates. The peaks of the current waves were predicted to be in the past for four countries (Italy, Spain, Germany and Switzerland) and to emerge in 0.5-2 weeks in Ireland and 1-3 weeks in the UK. For France one model estimated the peak within the past week and the other in the future in two weeks. Crucially, Maximum a posteriori (MAP) estimates of S0 for each country indicated effective population sizes of below 20% (of total population size), under both the continuous time and HMM models. Using for all countries, with a Bayesian weighted average across all seven countries and both models, we estimated that 6.4% of the total population would be immune. From the two models the maximum percentage of the effective population was estimated at 19.6% of the total population for the UK, 16.7% for Ireland, 11.4% for Italy, 12.8% for Spain, 18.8% for France, 4.7% for Germany and 12.9% for Switzerland. Conclusion: Our results indicate that after the current wave, a large proportion of the total population will remain without immunity. This suggests that in the absence of strong seasonal effects, new medications or more comprehensive contact tracing, a further set of epidemic waves in different geographic centres are likely. These findings may have implications for exit strategies from any lockdown stage.

negative: Fevers Are Rarest in the Morning: Could We Be Missing Infectious Disease Cases by Screening for Fever Then? Body temperatures are less likely to reach the fever range in the morning, but it is unknown how this affects practice during disease outbreaks. We retrospectively investigated fever-range temperatures ([≥]100.4{degrees}F, [≥]38.0{degrees}C) during seasonal influenza outbreaks and the 2009 H1N1 (swine flu) pandemic, which have recently been used as preparatory models for coronavirus disease 2019 (COVID-19). Our analyses included a nationally representative sample of records from adult visits to US emergency departments (n=202,181) and data from a Boston emergency department (n=93,225). Fever-range temperatures were about half as common in the morning as in the evening, suggesting that morning temperatures can be much less diagnostic, and that revisions may be needed to the practice of once-daily temperature screens at morning arrival to workplaces and schools. Twice-daily screens could be a simple solution, but similar research is still needed on fevers in COVID-19 itself.

negative: Decoding the lethal effect of SARS-CoV-2 (novel coronavirus) strains from global perspective: molecular pathogenesis and evolutionary divergence Background COVID-19 is a disease with global public health emergency that have shook the world since its’ first detection in China in December, 2019. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen responsible behind this pandemic. The lethality of different viral strains is found to vary in different geographical locations but the molecular mechanism is yet to be known. Methods Available data of whole genome sequencing of different viral strains published by different countries were retrieved and then analysed using Multiple Sequence Alignment and Pair-wise Sequence Alignment leading to Phylogenetic tree construction. Each location and the corresponding genetic variations were screened in depth. Then the variations are analysed at protein level giving special emphasis on Non Synonymous amino acid substitutions. The fatality rates in different countries were matched against the mutation number, rarity of the nucleotide alterations and functional impact of the Non Synonymous changes at protein level, separately and in combination. Findings All the viral strains have been found to evolve from the viral strain of Taiwan (MT192759) which is 100% identical with the ancestor SARS-CoV-2 sequences of Wuhan (NC 045512.2; submitted on 5th Jan, 2020). Transition from C to T (C>T) is the most frequent mutation in this viral genome and mutations A>T, G>A, T>A are the rarest ones, found in countries with maximum fatality rate i.e Italy, Spain and Sweden. 20 Non Synonymous mutations are located in viral genome spanning Orf1ab polyprotein, Surface glycoprotein, Nucleocapsid protein etc. The functional effect on the structure and function of the protein can favourably or unfavourably interact with the host body. Interpretation The fatality outcome depends on three important factors (a) number of mutation (b) rarity of the allelic variation and (c) functional consequence of the mutation at protein level. The molecular divergence, evolved from the ancestral strain (S) lead to extremely lethal (E), lethal(L) and non lethal (N) strains with the involvement of an Intermediate strain(I).

negative: Political Intrusions into the International Health Regulations Treaty and Its Impact on Management of Rapidly Emerging Zoonotic Pandemics: What History Tells Us For a large number of health care providers world-wide, the coronavirus disease 2019 (COVID-19) pandemic is their first experience in population-based care. In past decades, lower population densities, infectious disease outbreaks, epidemics, and pandemics were rare and driven almost exclusively by natural disasters, predatory animals, and war. In the early 1900s, Sir William Osler first advanced the knowledge of zoonotic diseases that are spread from reservoir animals to human animals. Once rare, they now make up 71% or more of new diseases. Globally, zoonotic spread occurs for many reasons. Because the human population has grown in numbers and density, the spread of these diseases accelerated though rapid unsustainable urbanization, biodiversity loss, and climate change. Furthermore, they are exacerbated by an increasing number of vulnerable populations suffering from chronic deficiencies in food, water, and energy. The World Health Organization (WHO) and its International Health Regulation (IHR) Treaty, organized to manage population-based diseases such as Influenza, severe acute respiratory syndrome (SARS), H1N1, Middle East respiratory syndrome (MERS), HIV, and Ebola, have failed to meet population-based expectations. In part, this is due to influence from powerful political donors, which has become most evident in the current COVID-19 pandemic. The global community can no longer tolerate an ineffectual and passive international response system, nor tolerate the self-serving political interference that authoritarian regimes and others have exercised over the WHO. In a highly integrated globalized world, both the WHO with its IHR Treaty have the potential to become one of the most effective mechanisms for crisis response and risk reduction world-wide. Practitioners and health decision-makers must break their silence and advocate for a stronger treaty, a return of the WHO's singular global authority, and support highly coordinated population-based management. As Osler recognized, his concept of "one medicine, one health" defines what global public health is today.

negative: Attempted early detection of influenza A (H1N1) pandemic with surveillance data of influenza‐like illness and unexplained pneumonia Please cite this paper as: Qian et al. (2011) Attempted early detection of influenza A (H1N1) pandemic with surveillance data of influenza‐like illness and unexplained pneumonia. Influenza and Other Respiratory Viruses 5(6), e479–e486. Background To collect disease information and provide data for early detection of epidemics, two surveillance systems were established for influenza‐like illness (ILI) and unexplained pneumonia (UP) in Wuxi, People’s Republic of China. Objectives The current study aims to describe the performance of these surveillance systems during 2004–2009 and to evaluate the value of surveillance data in detection of influenza epidemics. Methods Two national ILI sentinel hospitals and three UP sentinel hospitals provided data to the surveillance systems. The surveillance data from hospital‐based outpatient clinics and emergency rooms were compared by year. The ILI data of 2009 were further modeled based on previous data using both a control chart method and a moving average regression method. Alarms of potential epidemics would be raised when the input surveillance data surpassed a threshold. Results In 2009, the proportions of ILI and respiratory illness with fever (one surveillance syndrome of the UP system) to total patient visits (3·40% and 11·76%, respectively) were higher than the previous years. The surveillance data of both systems also showed developing trends similar to the influenza A (H1N1) pandemic in 2009. When the surveillance data of 2009 were fitted in the two detection models, alarms were produced on the occurrence of the first local case of influenza A (H1N1), outbreaks in schools and in general populations. Conclusions The results indicated the potential for using ILI and UP surveillance data as syndromic indicators to detect and provide an early warning for influenza epidemics.

negative: The Time for Universal Masking of the Public for Coronavirus Disease 2019 Is Now In this perspective, we recommend universal masking of the US public during coronavirus disease 2019 due to the high contagiousness of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), viral shedding of viable SARS-CoV-2 from asymptomatic individuals, and the likely contribution of masking to core distancing public health strategies for curbing transmission.

negative: Pollen likely seasonal factor in inhibiting flu-like epidemics. A Dutch study into the inverse relation between pollen counts, hay fever and flu-like incidence 2016–2019 Abstract There is uncertainty if current models for the Covid-19 pandemic should already take into account seasonality. That is because current environmental factors do not provide a powerful explanation of such seasonality, especially given climate differences between countries with moderate climates. It is hypothesized that one major factor is overlooked: pollen count. Pollen are documented to invoke strong immune responses and might create an environmental factor that makes it more difficult for flu-like viruses to survive outside a host. This Dutch study confirms that there is a (highly) significant inverse correlation between pollen count and weekly changes in medical flu consults, and that there is a highly significant inverse correlation between hay fever incidence, as measured by prescribed medication revenues, and weekly flu consults. This supports the idea that pollen are a direct or indirect factor in the seasonality of flu-like epidemics. If seasonality will be observed during the covid-19 spread as well, it is not unlikely that pollen play a role.

negative: Annotation of long non-coding RNAs expressed in Collaborative Cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions of host lncRNAs in response to influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) based on their similarity in expression with genes of known function. We performed total RNA-Seq on viral-infected lungs from eight mouse strains, yielding a large data set of transcriptional responses. Overall 5,329 lncRNAs were differentially expressed after infection. Most of the lncRNAs were co-expressed with coding genes in modules enriched in genes associated with lung homeostasis pathways or immune response processes. Each lncRNA was further individually annotated using a rank-based method, enabling us to associate 5,295 lncRNAs to at least one gene set and to predict their potential cis effects. We validated the lncRNAs predicted to be interferon-stimulated by profiling mouse responses after interferon-α treatment. Altogether, these results provide a broad categorization of potential lncRNA functions and identify subsets of lncRNAs with likely key roles in respiratory virus pathogenesis. These data are fully accessible through the MOuse NOn-Code Lung interactive database (MONOCLdb).

negative: Travellers give wings to novel coronavirus (2019-nCoV) A novel coronavirus, probably of bat origin, has caused an outbreak of severe respiratory infection in humans in Wuhan, China and has been dispersed globally by travelers. The WHO has declared the spread of the infection a Public Health Emergency of International Concern.

negative: The reaction of elderly Asian tourists to avian influenza and SARS Several cases of the H5N1 virus, or bird flu, have recently been discovered in Asia. In some isolated cases, the virus was found to have been transmitted from animals to human beings. However, most research suggested that the virus has low virulence in man. In 2005, the World Health Organisation urged vigilance, since as with other forms of influenza, the virus could mutate into form more easily communicable among human beings. As a result, some countries, issued travel alerts to their citizens to avoid all-but-essential travel to the affected areas. Visitors to Asian countries were told to avoid contact with and the consumption of poultry. This study investigates the impact of the avian influenza on elderly tourists in Asia, evaluating its findings in light of the earlier SARS outbreak in the region. It concludes that neither of these diseases significantly discouraged this group of tourists from undertaking their planned itineraries.

negative: General Guidelines in the Management of an Obstetrical Patient on the Labor and Delivery Unit during the COVID-19 Pandemic Novel coronavirus disease 2019 (COVID-19) is a respiratory tract infection that was first identified in China. Since its emergence in December 2019, the virus has rapidly spread, transcending geographic barriers. The World Health Organization and the Centers for Disease Control and Prevention have declared COVID-19 as a public health crisis. Data regarding COVID-19 in pregnancy is limited, consisting of case reports and small cohort studies. However, obstetric patients are not immune from the current COVID-19 pandemic, and obstetric care will inevitably be impacted by the current epidemic. As such, clinical protocols and practice on labor and delivery units must adapt to optimize the safety of patients and health care workers and to better conserve health care resources. In this commentary, we provide suggestions to meet these goals without impacting maternal or neonatal outcomes. KEY POINTS: â¢ Novel coronavirus disease 2019 (COVID-19) is a pandemic.â¢ COVID-19 impacts care of obstetric patients.â¢ Health care should be adapted for the COVID-19 pandemic.

negative: HEALTH STATUS OF LIVER TRANSPLANTED PATIENTS DURING THE CORONAVIRUS OUTBREAK IN ITALY: A LARGE SINGLE CENTER EXPERIENCE FROM MILAN

negative: Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR BACKGROUND: The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. AIM: We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. METHODS: Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. RESULTS: The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. CONCLUSION: The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.

negative: From “A”IV to “Z”IKV: Attacks from Emerging and Re-emerging Pathogens 100 years after the infamous “Spanish flu” pandemic, the 2017–2018 flu season has been severe, with numerous infections worldwide. In between, there have been continuous, relentless attacks from (re-)emerging viruses. To fully understand viral pathogenesis and develop effective medical countermeasures, we must strengthen current surveillance and basic research efforts.

negative: Clinical Manifestations of Children with COVID-19: a Systematic Review Context: The coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. Objective: To describe the clinical, laboratorial and radiological characteristics of children with COVID-19. Data Sources: The Medline database was searched between December 1st 2019 and March 30th 2020. Study Selection: Inclusion criteria were: (1) studied patients younger than 18 years old; (2) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (3) contained descriptions of clinical manifestations, laboratory tests or radiological examinations. Data Extraction: Number of cases, gender, age, clinical manifestations, laboratory tests, radiological examinations and outcomes. Results: A total of 34 studies (1,118 cases) were included. From all the cases, 1,111 had their severity classified: 14.3% were asymptomatic, 36.4% were mild, 46.0% were moderate, 2.2% were severe and 1.2% were critical. The most prevalent symptom was fever (16.3%), followed by cough (14.4%), nasal symptoms (3.6%), diarrhea (2.7%) and nausea/vomiting (2.5%). One hundred forty-five (12.9%) children were diagnosed with pneumonia and 43 (3.8%) upper airway infections were reported. Reduced lymphocyte count were reported in 13.1% of cases. Abnormalities on computed tomography was reported in 62.7% of cases. The most prevalent abnormalities reported were ground glass opacities, patchy shadows and consolidations. Only one death was reported. Conclusions: Clinical manifestations of children with COVID-19 differ widely from adults cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.

negative: Viral Kinetics and Antibody Responses in Patients with COVID-19 Background A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort. Methods We conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM). Results The median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011). Conclusions Nasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity.

negative: [Analysis of the pregnancy outcomes in pregnant women with COVID-19 in Hubei Province]. Objective: To study the effect of COVID-19 on pregnancy outcomes and neonatal prognosis in Hubei Province. Methods: A retrospective comparison of the pregnancy outcomes was done between 16 women with COVID-19 and 45 women without COVID-19. Also, the results of laboratory tests, imaging examinations, and the 2019-nCoV nucleic acid test were performed in 10 cases of neonatal deliverd from women with COVID-19. Results: (1) Of the 16 pregnant women with COVID-19, 15 cases were ordinary type and 1 case was severe type. No one has progressed to critical pneumonia. The delivery method of the two groups was cesarean section, and the gestational age were (38.7±1.4) and (37.9±1.6) weeks, there was no significant difference between the two groups (P> 0.05). Also, there wee no significant differences in the intraoperative blood loss and birth weight of the newborn between the two groups (all P>0.05). (2) Ten cases of neonates delivered from pregnant women with COVID-19 were collected. The 2019-nCoV nucleic acid test were all negative. There were no significant differences in fetal distress, meconium-stained amniotic fluid, preterm birth, and neonatal asphyxia between the two groups (all P>0.05). (3) In the treatment of uterine contraction fatigue, carbetocin or carboprost tromethamine was used more in cesarean section for pregnant women with COVID-19 (1.3±0.6), compared with Non-COVID-19 group (0.5±0.7), the difference was statistically significant (P=0.001). Conclusions: If there is an indication for obstetric surgery or critical illness of COVID-19 in pregnant women, timely termination of pregnancy will not increase the risk of premature birth and asphyxia of the newborn, but it is beneficial to the treatment and rehabilitation of maternal pneumonia. Preventive use of long-acting uterotonic agents could reduce the incidence of postpartum hemorrhage during surgery. 2019-nCoV infection has not been found in neonates deliverd from pregnant women with COVID-19.

negative: Nidovirales: Evolving the largest RNA virus genome Abstract This review focuses on the monophyletic group of animal RNA viruses united in the order Nidovirales. The order includes the distantly related coronaviruses, toroviruses, and roniviruses, which possess the largest known RNA genomes (from 26 to 32kb) and will therefore be called ‘large’ nidoviruses in this review. They are compared with their arterivirus cousins, which also belong to the Nidovirales despite having a much smaller genome (13–16kb). Common and unique features that have been identified for either large or all nidoviruses are outlined. These include the nidovirus genetic plan and genome diversity, the composition of the replicase machinery and virus particles, virus-specific accessory genes, the mechanisms of RNA and protein synthesis, and the origin and evolution of nidoviruses with small and large genomes. Nidoviruses employ single-stranded, polycistronic RNA genomes of positive polarity that direct the synthesis of the subunits of the replicative complex, including the RNA-dependent RNA polymerase and helicase. Replicase gene expression is under the principal control of a ribosomal frameshifting signal and a chymotrypsin-like protease, which is assisted by one or more papain-like proteases. A nested set of subgenomic RNAs is synthesized to express the 3′-proximal ORFs that encode most conserved structural proteins and, in some large nidoviruses, also diverse accessory proteins that may promote virus adaptation to specific hosts. The replicase machinery includes a set of RNA-processing enzymes some of which are unique for either all or large nidoviruses. The acquisition of these enzymes may have improved the low fidelity of RNA replication to allow genome expansion and give rise to the ancestors of small and, subsequently, large nidoviruses.

negative: COVID: How to explain differences in lethality between different populations?

negative: The COVID-19 pandemic and health inequalities This essay examines the implications of the COVID-19 pandemic for health inequalities. It outlines historical and contemporary evidence of inequalities in pandemics—drawing on international research into the Spanish influenza pandemic of 1918, the H1N1 outbreak of 2009 and the emerging international estimates of socio-economic, ethnic and geographical inequalities in COVID-19 infection and mortality rates. It then examines how these inequalities in COVID-19 are related to existing inequalities in chronic diseases and the social determinants of health, arguing that we are experiencing a syndemic pandemic. It then explores the potential consequences for health inequalities of the lockdown measures implemented internationally as a response to the COVID-19 pandemic, focusing on the likely unequal impacts of the economic crisis. The essay concludes by reflecting on the longer-term public health policy responses needed to ensure that the COVID-19 pandemic does not increase health inequalities for future generations.

negative: Emerging Viruses Emerging viruses are viruses that appear suddenly in the human population. These are viruses to which man has no history of exposure and thus no or limited immunity; they are not new evolutionary creations, but are viruses than man meets due to environmental changes, such as deforestation, entering into new habitats, or viruses that are transmitted from one species of animal to humans. Most of these viruses are terrifying, and cause hemorrhagic fever, a complete destruction of the circulation system; they include Lassa fever, Nipah virus, Ebola, HIV, Severe acute respiratory syndrome (SARS), and, recently, Middle East respiratory syndrome (MERS), which is the latest in a series of “new” respiratory viruses infecting man. It is possible that unknown emerging viruses are the cause of death, often listed as “death due to an unknown cause,” as in the retrospective cases of HIV. Emerging viruses might also include poliovirus and influenza, since their introduction into the human population is (was) often sudden and due to changes in the environment or due to contact with other animal species. For examples, polio was a result of changes in sanitation in the countries of North America and Western Europe, and influenza is constantly jumping from aquatic birds to man and other animal species where genomic reassortment occurs.

negative: COVID-19: Immunology and treatment options Abstract The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.

negative: Evaluation of twenty‐two rapid antigen detection tests in the diagnosis of Equine Influenza caused by viruses of H3N8 subtype BACKGROUND: Equine influenza (EI) is a highly contagious disease caused by viruses of the H3N8 subtype. The rapid diagnosis of EI is essential to reduce the disease spread. Many rapid antigen detection (RAD) tests for diagnosing human influenza are available, but their ability to diagnose EI has not been systematically evaluated. OBJECTIVES: The aim of this study was to compare the performance of 22 RAD tests in the diagnosis of EI. METHODS: The 22 RAD tests were performed on fivefold serial dilutions of EI virus to determine their detection limits. The four most sensitive RAD tests (ImmunoAce Flu, BD Flu examan, Quick chaser Flu A, B and ESPLINE Influenza A&B‐N) were further evaluated using nasopharyngeal samples collected from experimentally infected and naturally infected horses. The results were compared to those obtained using molecular tests. RESULTS: The detection limits of the 22 RAD tests varied hugely. Even the four RAD tests showing the best sensitivity were 125‐fold less sensitive than the molecular techniques. The duration of virus detection in the experimentally infected horses was shorter using the RAD tests than using the molecular techniques. The RAD tests detected between 27% and 73% of real‐time RT‐PCR‐positive samples from naturally infected horses. CONCLUSIONS: The study demonstrated the importance of choosing the right RAD tests as only three of 22 were fit for diagnosing EI. It was also indicated that even RAD tests with the highest sensitivity serve only as an adjunct to molecular tests because of the potential for false‐negative results.

negative: A single centre study of viral community-acquired pneumonia in children: no evidence of SARS-CoV-2 from October 2019 to March 2020 Abstract Pneumonia is an important cause of morbidity and mortality in children. We described viral aetiologies, with particular interest in detecting SARS-CoV-2, in hospitalized pneumonia children. Human rhinovirus was the most frequently detected agent. No children tested positive for SARS-CoV-2. Our findings suggest that SARS-CoV-2 infection is rare in children and it was not circulating in Rome before COVID-19 outbreak.

negative: Differences in power-law growth over time and indicators of COVID-19 pandemic progression worldwide An automated statistical and error analysis of 45 countries or regions with more than 1000 cases of COVID-19 as of March 28, 2020, has been performed. This study reveals differences in the rate of disease spreading rate over time in different countries. This survey observes that most countries undergo a beginning exponential growth phase, which transitions into a power-law phase, as recently suggested by Ziff and Ziff. Tracking indicators of growth, such as the power-law exponent, are a good indication of the relative danger different countries are in and show when social measures are effective towards slowing the spread. The data compiled here are usefully synthesizing a global picture, identifying country to country variation in spreading, and identifying countries most at risk. This analysis may factor into how best to track the effectiveness of social distancing policies and quarantines in real-time as data is updated each day.

negative: Performance evaluation of direct fluorescent antibody, Focus Diagnostics Simplexa™ Flu A/B & RSV and multi-parameter customized respiratory Taqman® array card in immunocompromised patients Abstract Background Molecular assays for diagnosis of Flu A, Flu B, and RSV with short turn-around-time (TAT) are of considerable clinical importance. In addition, rapid and accurate diagnosis of a large panel of viral and atypical pathogens can be crucial in immunocompromised patients. Objectives First, to evaluate the performance of the Simplexa™ Direct assay system in comparison with direct fluorescent antibody (DFA) and customized Taqman® Array Card (TAC) testing for RSV, Flu A, and Flu B in immunocompromised patients. Second, to evaluate different algorithms for the detection of respiratory pathogens in terms of cost, turn-around-time (TAT) and diagnostic yield. Study design We collected 125 nasopharyngeal swabs (NTS) and 25 BAL samples from symptomatic immunocompromised patients. Samples for which Simplexa™ and TAC results were discordant underwent verification testing. The TAC assay is based on singleplex RT-PCR, targeting 24 viruses, 8 bacteria and 2 fungi simultaneously. Results The overall sensitivity was significantly lower for DFA testing than for the two molecular methods (p <0.05). Performance characteristics of Simplexa™ testing were not significantly different compared to TAC testing (p >0.1). For BAL samples only, the sensitivity and specificity of the Simplexa™ assay was 100%. In total, 6.7, 16 and 18% of samples were positive for Flu A, Flu B or RSV by DFA, Simplexa™ and TAC testing, respectively. When considering not only these pathogens but also all results for TAC, the method identified 93 samples with one or more respiratory pathogens (62%). A co-infection rate of 15.3% was found by TAC. The estimated costs and TAT were 8.2€ and 2h for DFA, 31.8€ and 1.5h for Simplexa™ and 55€ and 3h for TAC testing. Conclusions Performing the Simplexa™ test 24h a day/7 days a week instead of DFA would considerably improve the overall sensitivity and time-to-result, albeit at a higher cost generated in the laboratory. Performing the TAC would increase the diagnostic yield and detection of co-infections significantly.

negative: Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK’s largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity.

negative: Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections.

negative: Emergence of Novel Coronavirus and COVID-19: whether to stay or die out? The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus "SARS-CoV-2" (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect naïve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.

negative: Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses. Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease. Here, we describe a new technology that automatically collects body temperatures during triage. The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics. METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs. Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer. The data were summarized in terms of rates of fever (temperatures ≥100.4 °F [≥38.0 °C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts. RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers. The period of study included the autumn–winter wave of the 2009–2010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010–2011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %. The periods of peak fever rates corresponded with the periods of regionally elevated flu activity. CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years. The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems. Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical. However, the system’s validity and generalizability should be evaluated in additional years and settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.

negative: Does culture matter social distancing under the COVID-19 pandemic? This paper is the first to examine the role of the cultural dimension in practising social distancing across the world. By drawing the data from the Google COVID-19 community mobility reports and the Hofstede cultural factors for 58 countries over the period from 16 February to 29 March 2020, we find that countries with higher ‘Uncertainty Avoidance Index’ predict the lower proportion of people gathering in public such as retail and recreation, grocery and pharmacy, parks, transit stations, workplaces. However, we do not find any predictive factor in having a relationship with the percentage of citizens staying in their residential areas. Our results are robust by adding the control variable as the wealth status, GDP per capita. Hence, this paper suggests some effective communications to contain the COVID-19 pandemic by emphasizing the role of uncertainties.

negative: Transmission dynamics of SARS-COV-2 in China: impact of public health interventions COVID-19 has become a global pandemic. However, the impact of the public health interventions in China needs to be evaluated. We established a SEIRD model to simulate the transmission trend of China. In addition, the reduction of the reproductive number was estimated under the current forty public health interventions policies. Furthermore, the infection curve, daily transmission replication curve, and the trend of cumulative confirmed cases were used to evaluate the effects of the public health interventions. Our results showed that the SEIRD curve model we established had a good fit and the basic reproductive number is 3.38 (95% CI, 3.25-3.48). The SEIRD curve show a small difference between the simulated number of cases and the actual number; the correlation index (H2) is 0.934, and the reproductive number (R) has been reduced from 3.38 to 0.5 under the current forty public health interventions policies of China. The actual growth curve of new cases, the virus infection curve, and the daily transmission replication curve were significantly going down under the current public health interventions. Our results suggest that the current public health interventions of China are effective and should be maintained until COVID-19 is no longer considered a global threat.

negative: Influence of COVID-19 confinement in students performance in higher education This study explores the effects of COVID-19 confinement in the students performance in higher education. Using a field experiment of 458 students from three different subjects in Universidad Autonoma de Madrid (Spain), we study the differences in assessments by dividing students into two groups. The first group (control) corresponds to academic years 2017/2018 and 2018/2019. The second group (experimental) corresponds to students from 2019/2020, which is the group of students that interrupted their face-to-face activities because of the confinement. The results show that there is a significant positive effect of the COVID-19 confinement on students performance. This effect is also significative in activities that did not change their format when performed after the confinement. We find that this effect is significative both in subjects that increased the number of assessment activities and subjects that did not change the workload of students. Additionally, an analysis of students learning strategies before confinement shows that students did not study in a continuous basis. Based on these results, we conclude that COVID-19 confinement changed students learning strategies to a more continuous habit, improving their efficiency. For these reasons, better scores in students assessment are expected due to COVID-19 confinement that can be explained by an improvement in their learning performance.

negative: COVID-19: Development of a robust mathematical model and simulation package with consideration for ageing population and time delay for control action and resusceptibility The current global health emergency triggered by the pandemic COVID-19 is one of the greatest challenges mankind face in this generation. Computational simulations have played an important role to predict the development of the current pandemic. Such simulations enable early indications on the future projections of the pandemic and is useful to estimate the efficiency of control action in the battle against the SARS-CoV-2 virus. The SEIR model is a well-known method used in computational simulations of infectious viral diseases and it has been widely used to model other epidemics such as Ebola, SARS, MERS, and influenza A. This paper presents a modified SEIRS model with additional exit conditions in the form of death rates and resusceptibility, where we can tune the exit conditions in the model to extend prediction on the current projections of the pandemic into three possible outcomes; death, recovery, and recovery with a possibility of resusceptibility. The model also considers specific information such as ageing factor of the population, time delay on the development of the pandemic due to control action measures, as well as resusceptibility with temporal immune response. Owing to huge variations in clinical symptoms exhibited by COVID-19, the proposed model aims to reflect better on the current scenario and case data reported, such that the spread of the disease and the efficiency of the control action taken can be better understood. The model is verified using two case studies for verification and prediction studies, based on the real-world data in South Korea and Northern Ireland, respectively.

negative: First genome sequences of buffalo coronavirus from water buffaloes in Bangladesh We report the complete genome sequences of a buffalo coronavirus (BufCoV HKU26) detected from the faecal samples of two domestic water buffaloes (Bubalus bubalis) in Bangladesh. They possessed 98–99% nucleotide identities to bovine coronavirus (BCoV) genomes, supporting BufCoV HKU26 as a member of Betacoronavirus 1. Nevertheless, BufCoV HKU26 possessed distinct accessory proteins between spike and envelope compared to BCoV. Sugar-binding residues in the N-terminal domain of S protein in BCoV are conserved in BufCoV HKU26.

negative: Genomic characterization of equine coronavirus Abstract The complete genome sequence of the first equine coronavirus (ECoV) isolate, NC99 strain was accomplished by directly sequencing 11 overlapping fragments which were RT–PCR amplified from viral RNA. The ECoV genome is 30,992 nucleotides in length, excluding the polyA tail. Analysis of the sequence identified 11 open reading frames which encode two replicase polyproteins, five structural proteins (hemagglutinin esterase, spike, envelope, membrane, and nucleocapsid) and four accessory proteins (NS2, p4.7, p12.7, and I). The two replicase polyproteins are predicted to be proteolytically processed by three virus-encoded proteases into 16 non-structural proteins (nsp1–16). The ECoV nsp3 protein had considerable amino acid deletions and insertions compared to the nsp3 proteins of bovine coronavirus, human coronavirus OC43, and porcine hemagglutinating encephalomyelitis virus, three group 2 coronaviruses phylogenetically most closely related to ECoV. The structure of subgenomic mRNAs was analyzed by Northern blot analysis and sequencing of the leader–body junction in each sg mRNA.

negative: Coronavirus Goes Viral: Quantifying the COVID-19 Misinformation Epidemic on Twitter Background Since the beginning of the coronavirus disease 2019 (COVID-19) epidemic, misinformation has been spreading uninhibited over traditional and social media at a rapid pace. We sought to analyze the magnitude of misinformation that is being spread on Twitter (Twitter, Inc., San Francisco, CA) regarding the coronavirus epidemic. Materials and methods We conducted a search on Twitter using 14 different trending hashtags and keywords related to the COVID-19 epidemic. We then summarized and assessed individual tweets for misinformation in comparison to verified and peer-reviewed resources. Descriptive statistics were used to compare terms and hashtags, and to identify individual tweets and account characteristics. Results The study included 673 tweets. Most tweets were posted by informal individuals/groups (66%), and 129 (19.2%) belonged to verified Twitter accounts. The majority of included tweets contained serious content (91.2%); 548 tweets (81.4%) included genuine information pertaining to the COVID-19 epidemic. Around 70% of the tweets tackled medical/public health information, while the others were pertaining to sociopolitical and financial factors. In total, 153 tweets (24.8%) included misinformation, and 107 (17.4%) included unverifiable information regarding the COVID-19 epidemic. The rate of misinformation was higher among informal individual/group accounts (33.8%, p: <0.001). Tweets from unverified Twitter accounts contained more misinformation (31.0% vs 12.6% for verified accounts, p: <0.001). Tweets from healthcare/public health accounts had the lowest rate of unverifiable information (12.3%, p: 0.04). The number of likes and retweets per tweet was not associated with a difference in either false or unverifiable content. The keyword “COVID-19” had the lowest rate of misinformation and unverifiable information, while the keywords “#2019_ncov” and “Corona” were associated with the highest amount of misinformation and unverifiable content respectively. Conclusions Medical misinformation and unverifiable content pertaining to the global COVID-19 epidemic are being propagated at an alarming rate on social media. We provide an early quantification of the magnitude of misinformation spread and highlight the importance of early interventions in order to curb this phenomenon that endangers public safety at a time when awareness and appropriate preventive actions are paramount.

negative: Global response to pandemic flu: more research needed on a critical front If and when sustained human-to-human transmission of H5N1 becomes a reality, the world will no longer be dealing with sporadic avian flu borne along migratory flight paths of birds, but aviation flu – winged at subsonic speed along commercial air conduits to every corner of planet Earth. Given that air transportation is the one feature that most differentiates present day transmission scenarios from those in 1918, our present inability to prevent spread of influenza by international air travel, as reckoned by the World Health Organization, constitutes a major weakness in the current global preparedness plan against pandemic flu. Despite the lessons of SARS, it is surprising that aviation-related health policy options have not been more rigorously evaluated, or scientific research aimed at strengthening public health measures on the air transportation front, more energetically pursued.

negative: Of Viruses, Vaccines, and Variability: Qualitative Meaning Matters Abstract Deaths from COVID-19 depend on millions of people understanding risk and translating this understanding into risk-reduction behaviors. Although numerical information about risk is helpful, numbers are surprisingly ambiguous, and there are predictable mismatches in risk perception between laypeople and experts. Hence, risk communication should convey the qualitative, contextualized meaning of risk.

negative: Influenza vaccine coverage rates and perceptions on vaccination in South Korea Summary Objective This survey was performed to assess the level of influenza vaccine coverage, to understand the driving forces and barriers to vaccination and determine vaccination interventions for the following year in Korean population. Methods A national sample of 1720 community dwelling adults of age 18 and older were surveyed by individual visits during April 2005. Demographics, state of influenza vaccination, reasons for vaccination or non-vaccination and perceptions on vaccinations were asked by questionnaire. Results Influenza vaccination coverage in general population and high risk group was 34.3% and 61.3%, respectively. Predictors for vaccination were ≥65 of age, performance of regular exercise, vaccination in the previous season, experience of influenza-like illness, belief that vaccine can prevent common cold and opinion that vaccine must be taken annually. The most common reason for vaccination for both whole population and high risk groups was to prevent both influenza and common cold, while the most common reason for non-vaccination was the thought that he/she was healthy enough not to be in need for vaccination. Having more information on influenza and vaccination as well as doctor's recommendation for vaccination appeared to be the most important modus operandi to encourage influenza vaccination among non-vaccinees. Conclusions Doctor's recommendation was the most important factor in encouraging people to be vaccinated against influenza. Doctors should be geared up with precise information and actively encourage high risk population in order to increase vaccination coverage.

negative: Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA) and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0193-x) contains supplementary material, which is available to authorized users.

negative: Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes We analyse global data for COVID-19 deaths and recoveries and show that outbreak severity displays a striking latitude relationship with a northern hemisphere bias. Transmission rates can be explained by seasonal weather conditions, but this does not account for observed variations in fatality rates. Many factors point to Vitamin D as a candidate explanation but historical controversy surrounding Vitamin D studies and the lack of a coherent framework for causal inference has hampered acceptance of this explanation despite a wealth of evidence in its favour. We analyse global COVID-19 data using Causal Inference, constructing two contrasting directed acyclic graph (DAG) models, one causal and one acausal, and set out clearly multiple predictions made by each model. We show that observed data strongly match predictions made by the causal model but largely contradict those of the acausal model. We explore historic evidence further supporting the causal model. We review biochemical mechanisms that may explain the various ways in which vitamin D acts. We detail the mechanisms by which the SARS-Cov-2 virus causes the disease and known pathways that involve Vitamin D and show how these both protect against viral infection, as well as ameliorating disease symptoms in COVID-19 and other respiratory diseases. We examine the factors that govern confidence in causal inference models and conclude that a high level of confidence in a causal beneficial role for Vitamin D is justified.

negative: Perspective: COVID-19, implications of nasal diseases and consequences for their management

negative: Trends of SARS-Cov-2 infection in 67 countries: Role of climate zone, temperature, humidity and curve behavior of cumulative frequency on duplication time Summary Objective. To analyze the role of temperature, humidity, date of first case diagnosed (DFC) and the behavior of the growth-curve of cumulative frequency (CF) [number of days to rise (DCS) and reach the first 100 cases (D100), and the difference between them (ΔDD)] with the doubling time (Td) of Covid-19 cases in 67 countries grouped by climate zone. Design. Retrospective incident case study. Setting. WHO based register of cumulative incidence of Covid-19 cases. Participants. 1,706,914 subjects diagnosed between 12-29-2019 and 4-15-2020. Exposures. SARS-Cov-2 virus, ambient humidity, temperature and climate areas (temperate, tropical/subtropical). Main outcome measures. Comparison of DCS, D100, ΔDD, DFC, humidity, temperature, Td for the first (Td10) and second (Td20) ten days of the CF growth-curve between countries according to climate zone, and identification of factors involved in Td, as well as predictors of CF using lineal regression models. Results. Td10 and Td20 were ≥3 days longer in tropical/subtropical vs. temperate areas (2.8[plusmn]1.2 vs. 5.7[plusmn]3.4; p=1.41E-05 and 4.6[plusmn]1.8 vs. 8.6[plusmn]4.2; p=9.7E-05, respectively). The factors involved in Td10 (DFC and ΔDD) were different than those in Td20 (Td10 and climate areas). After D100, the fastest growth-curves during the first 10 days, were associated with Td10<2 and Td10<3 in temperate and tropical/subtropical countries, respectively. The fold change Td20/Td10 >2 was associated with earlier flattening of the growth-curve. In multivariate models, Td10, DFC and ambient temperature were negatively related with CF and explained 44.7% (r2 = 0.447) of CF variability at day 20 of the growth-curve, while Td20 and DFC were negatively related with CF and explained 63.8% (r2 = 0.638) of CF variability towards day 30 of the growth-curve. Conclusions. The larger Td in tropical/subtropical countries is positively related to DFC and temperature. Td and environmental factors explain 64% of CF variability in the best of cases. Therefore, other factors, such as pandemic containment measures, would explain the remaining variability.

negative: Detection of Covid-19 From Chest X-ray Images Using Artificial Intelligence: An Early Review In 2019, the entire world is facing a situation of health emergency due to a newly emerged coronavirus (COVID-19). Almost 196 countries are affected by covid-19, while USA, Italy, China, Spain, Iran, and France have the maximum active cases of COVID-19. The issues, medical and healthcare departments are facing in delay of detecting the COVID-19. Several artificial intelligence based system are designed for the automatic detection of COVID-19 using chest x-rays. In this article we will discuss the different approaches used for the detection of COVID-19 and the challenges we are facing. It is mandatory to develop an automatic detection system to prevent the transfer of the virus through contact. Several deep learning architecture are deployed for the detection of COVID-19 such as ResNet, Inception, Googlenet etc. All these approaches are detecting the subjects suffering with pneumonia while its hard to decide whether the pneumonia is caused by COVID-19 or due to any other bacterial or fungal attack.

negative: Are dental schools adequately preparing dental students to face outbreaks of infectious diseases such as COVID-19? The recent 2019-novel coronavirus (2019-nCoV, also known as SARS-CoV-2) has caused >2,622,571 confirmed cases of coronavirus disease 2019 (COVID-19) in >185 countries, and >182,359 deaths globally. More than 9000 healthcare workers have also been infected by 2019-nCoV. Prior to the present pandemic of COVID-19, there have been multiple large-scale epidemics and pandemics of other viral respiratory infections, such as seasonal flu, Spanish flu (H1N1), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and others. Dental professionals are at an increased risk for contracting these viruses from dental patients, as dental practice involves face-to-face communication with the patients and frequent exposure to saliva, blood, and other body fluids. Dental education can play an important role in the training of dentists, helping them to adopt adequate knowledge and attitudes related to infection control measures. The current dental curriculum does not cover infection control adequately, especially from airborne pathogens. Infection control education needs to be included in the dental curriculum itself, and students should be trained adequately to protect them and prevent the infection from disseminating even before they see their first patient.

negative: Global research trend in the treatment of the new Coronavirus diseases (COVID-19) : bibliometric analysis. The Coronavirus 2019 (COVID-19) pandemic has caused worldwide concern and has become a major medical problem. Vaccines and therapeutics are important interventions for the management of this outbreak. This study aims to used bibliometric methods to identify research trends in the domain of therapeutics and vaccines to cure patients with COVID-19 since the beginning of the pandemic. The Web of Science Core Collection database was retrieved for articles on therapeutic approaches to coronavirus disease management published between January 1, 2020 and May 20, 2020. Identified and analyzed the data included title, corresponding author, language, publication time, publication type, research focus. A total of 1569 articles on coronavirus therapeutic means from 84 countries were published in 620 journals. We note the remarkable progressive increase in the number of publications related to research on therapies and vaccines for COVID-19. The United States provided the largest number of articles (405), followed by China (364). Journal of Medical Virology published most of them (n=40). 1005 (64.05%) were articles, 286 (18.23%) were letters, 230 (14.66%) were reviews. The terms "COVID- 19" or "SARS-CoV-2" or "Coronavirus" or "hydroxychloroquine" or "chloroquine" or "2019-nCOV" or "ACE2" or "treatment" or "remdesivir" or "pneumonia" were most frequently used, as shown in the density visualization map. A network analysis based on keyword co-occurrence revealed five distinct types of studies: clinical, biological, epidemiological, pandemic management, and therapeutics (vaccines and treatments). COVID-19 is a major disease that has had an impact on international public health at the global level. Several avenues for treatment and vaccines have been explored. Most of them focus on older drugs used to treat other diseases that have been effective for other types of coronaviruses. There is a discrepancy in the results obtained from the studies of the drugs included in this study. Randomized clinical trials are needed to evaluate older drugs and develop new treatment options.

negative: ElaD, a Deubiquitinating Protease Expressed by E. coli BACKGROUND: Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases. One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses. FINDINGS: We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs). Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria. CONCLUSION: The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity. As a counterpoint, our phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an early common origin of this peptidase clan.

negative: Pandemic Influenza: Potential Contribution to Disease Burden Records of disease outbreaks resembling influenza date to the writings of Hippocrates (fifth century BPE). Since then, influenza has afflicted humans around the globe. The most severe (“Spanish Flu” 10.1007/978-0-387-78665-0_6287) of three major outbreaks of the twentieth century killed approximately 20–50 million people worldwide. More recently, the global spread of highly pathogenic bird-adapted strain H5N1 is considered a significant pandemic threat. Since 2003, a total of 379 cases and 239 deaths have been reported. This chapter provides an overview of the genetic characteristics of the virus that elucidate its ability to continuously evade a host’s immune system; it describes some of the approaches used to quantify the burden of influenza and discusses their implications for the prevention and containment of future pandemics. The preliminary findings of the studies discussed here suggest that influenza-related burden is highly underestimated in tropical and subtropical regions of the world. This implicates that proper assessment of influenza-related morbidity and mortality worldwide is essential in planning and allocating resources to protect against what could be one of mankind’s most devastating challenges. A summary of learned lessons from past influenza pandemics are described and new intervention strategies aim at curtailing a future pandemic are discussed. More importantly, however, is the discussion of today’s challenges such as antiviral resistance, limited resources in a world that is globally connected and the imminent gap between the capacity (resources available) of developed and developing parts of the world to respond to a pandemic.

negative: Coronavirus disease 2019 (COVID-19): What we need to know

negative: Influenza Vaccination Is Not Associated With Detection of Noninfluenza Respiratory Viruses in Seasonal Studies of Influenza Vaccine Effectiveness Background. The test-negative control study design is the basis for observational studies of influenza vaccine effectiveness (VE). Recent studies have suggested that influenza vaccination increases the risk of noninfluenza respiratory virus infection. Such an effect could create bias in VE studies using influenza-negative controls. We investigated the association between influenza infection, vaccination, and detection of other respiratory viruses among children <5 years old and adults ≥50 years old with acute respiratory illness who participated in seasonal studies of influenza vaccine effectiveness. Methods. Nasal/nasopharyngeal samples collected from 2004–2005 through 2009–2010 were tested for 19 respiratory virus targets using a multiplex reverse-transcription polymerase chain reaction (RT-PCR) platform. Vaccination status was determined using a validated registry. Adjusted odds ratios for influenza and vaccination status were calculated using three different control groups: influenza-negative, other respiratory virus positive, and pan-negative. Results. Influenza was detected in 12% of 2010 children and 20% of 1738 adults. Noninfluenza respiratory viruses were detected in 70% of children and 38% of adults without influenza. The proportion vaccinated did not vary between virus-positive controls and pan-negative controls in children (P = .62) or adults (P = .33). Influenza infection was associated with reduced odds of vaccination, but adjusted odds ratios differed by no more than 0.02 when the analysis used influenza-negative or virus-positive controls. Conclusions. Influenza vaccination was not associated with detection of noninfluenza respiratory viruses. Use of influenza-negative controls did not generate a biased estimate of vaccine effectiveness due to an effect of vaccination on other respiratory virus infections.

negative: Challenges and Strategies of Laboratory Diagnosis for Newly Emerging Influenza Viruses in Taiwan: A Decade after SARS Since the first case of severe acute respiratory syndrome (SARS) in Taiwan was identified in March 2003, viral respiratory infections, in particular the influenza virus, have become a national public health concern. Taiwan would face a serious threat of public health problems if another SARS epidemic overlapped with a flu outbreak. After SARS, the Taiwan Centers for Disease Control accelerated and strengthened domestic research on influenza and expanded the exchange of information with international counterparts. The capacity of influenza A to cross species barriers presents a potential threat to human health. Given the mutations of avian flu viruses such as H7N9, H6N1, and H10N8, all countries, including Taiwan, must equip themselves to face a possible epidemic or pandemic. Such preparedness requires global collaboration.

negative: Surveillance of 16 respiratory viruses in patients with influenza‐like illness in Nanjing, China Much less is known about the etiology of influenza‐like illness in China. A continuous surveillance of 16 respiratory viruses was conducted from November 2010 to October 2011 of outpatients with influenza‐like illness in Nanjing, China. The two largest general hospitals and a provincial virus laboratory in Nanjing participated in this study. Throat swabs were collected from outpatients during medical visits for influenza‐like illness and were tested for 16 respiratory viruses using PCR. Three hundred seventeen viruses were detected in samples from 246 (50.6%) patients with influenza‐like illness. The viruses found mostly commonly were influenza, rhinovirus, hCoV HKU1, and adenovirus. The identification rates of respiratory viruses differed significantly among different sampling seasons (P = 0.0002). The rates of influenza A and hCoV HKU1 were much higher during the influenza‐like illness winter peak than during the influenza‐like illness summer peak and other months. Co‐infections were detected in 57 (11.7%) patients and were found most commonly in adults older than 60 years. RSV was detected in 5.9% and 2.6% of patients who were 0–5 and 6–15 years old, respectively, but was not detected in other age groups. This study confirmed that multiple respiratory viruses may circulate concurrently in the population and account for a large proportion of influenza‐like illness. In addition to influenza virus, hCoV HKU1 may be associated with the influenza‐like illness winter peak in Nanjing, China. J. Med. Virol. 84:1980–1984, 2012. © 2012 Wiley Periodicals, Inc.

negative: Simulation-based Estimation of the Spread of COVID-19 in Iran Background: The 2019 Coronavirus (COVID-19) has turned into a global pandemic with unprecedented challenges for the global community. Understanding the state of the disease and planning for future trajectories relies heavily on data on the spread and mortality. Yet official data coming from various countries are highly unreliable: symptoms similar to common cold in majority of cases and limited screening resources and delayed testing procedures may contribute to under-estimation of the burden of disease. Anecdotal and more limited data are available, but few have systematically combined those with official statistics into a coherent view of the epidemic. This study is a modeling-in-real-time of the emerging outbreak for understanding the state of the disease. Our focus is on the case of the spread of disease in Iran, as one of the epicenters of the disease in the first months of 2020. Method: We develop a simple dynamic model of the epidemic to provide a more reliable picture of the state of the disease based on existing data. Building on the generic SEIR (Susceptible, Exposed, Infected, and Recovered) framework we incorporate two behavioral and logistical considerations. First we capture the endogenous changes in contact rate (average contact per person) as more death are reported. As a result the reproduction number changes endogenously in the model. Second we differentiate reported and true cases by including simple formulations for how only a fraction of cases might be diagnosed, and how that fraction changes in response to epidemic's progression. In estimating the model we use both the official data as well as the discovered infected travelers and unofficial medical community estimates and triangulate these sources to build a more complete picture. Calibration is completed by forming a likelihood function for observing the actual time series data conditional on model parameters, and conducting a Markov Chain Monte Carlo simulations. The model is used to estimate current "true" cases of infection and death. We analyze the future trajectory of the disease under six conditions related to the seasonal effects and policy measures targeting social distancing. Findings: The model closely replicates the past data but also shows the true number of cases is likely far larger. We estimate about 493,000 current infected cases (90% CI: 271K-810K) as of March 20th, 2020. Our estimate for cumulative cases of infection until that date is 916,000 (90% CI: 508K, 1.5M), and for total death is 15,485 (90% CI: 8.4K, 25.8K). These numbers are significantly (more than one order of magnitude) higher than official statistics. The trajectory of the epidemic until the end of June could take various paths depending on the impact of seasonality and policies targeting social distancing. In the most optimistic scenario for seasonal effects, depending on policy measures, 1.6 million Iranians (90% CI: 0.9M-2.6M) are likely to get infected, and death toll will reach about 58,000 cases (90% CI: 32K-97K), while in the more pessimistic scenarios, death toll may exceed 103,000 cases (90% CI: 56K-172K). Implication: Our results suggest that the number of cases and deaths may be over an order of magnitude larger than official statistics in Iran. Absent extended testing capacity other countries may face a significant under-count of existing cases and thus be caught off guard about the actual toll of the epidemic.

negative: How necessary is a fast testkit for mitigation of pandemic flu? It is widely feared that a novel, highly pathogenic, human transmissible influenza virus may evolve that could cause the next global pandemic. Mitigating the spread of such an influenza pandemic would require not only the timely administration of antiviral drugs to those infected, but also the implementation of suitable intervention policies for stunting the spread of the virus. Towards this end, mathematical modelling and simulation studies are crucial as they allow us to evaluate the predicted effectiveness of the various intervention policies before enforcing them. Diagnosis plays a vital role in the overall pandemic management framework by detecting and distinguishing the pathogenic strain from the less threatening seasonal strains and other influenza-like illnesses. This allows treatment and intervention to be deployed effectively, given limited antiviral supplies and other resources. However, the time required to design a fast and accurate testkit for novel strains may limit the role of diagnosis. Herein, we aim to investigate the cost and effectiveness of different diagnostic methods using a stochastic agent-based city-scale model, and then address the issue of whether conventional testing approaches, when used with appropriate intervention policies, can be as effective as fast testkits in containing a pandemic outbreak. We found that for mitigation purposes, fast and accurate testkits are not necessary as long as sufficient medication is given, and are generally recommended only when used with extensive contact tracing and prophylaxis. Additionally, in the event of insufficient medication and fast testkits, the use of slower, conventional testkits together with proper isolation policies while waiting for the diagnostic results can be an equally effective substitute.

negative: Otitis Media and Sinusitis Otitis media (OM) and sinusitis are common and costly maladies that are often preceded by the development of a viral upper respiratory infection (vURI). Although antibiotics have been shown to be somewhat effective in the treatment of these disorders, increasing concern over the emergence of pathogen resistence to these agents underscores the need for the development of other treatment options, including agents to treat and/or prevent vURIs. Earlier research implicated roles for cytopathology, cellular infiltration, and inflammatory mediators such as bradykinin, in the pathogenesis of vURIs and its complications, including OM and sinusitis, but these factors are now recognized as late events with specific and limited contributions to disease expression. Current therapies are relatively ineffective and aimed at reducing symptoms rather than moderating underlying mechanisms. Nasal elevations of proinflammatory cytokines and leukotrienes track symptom expression during vURIs, and it is hypothesized that these chemicals orchestrate a common response to infection with many different viruses causing vURIs. Moreover, recent evidence demonstrates that specific cytokine gene polymorphisms may modulate the severity of illness and incidence of complications during episodes of vURI. Additionally, other evidence supports a role for neurogenic inflammation in the development of complications. Future studies should dissect the role of proinflammatory cytokines, leukotrienes, and neuropeptides in the expression of symptoms, signs, pathophysiologies, and complications of vURIs.

negative: Comparison of Cepheid® Xpert Flu and Roche RealTime Ready Influenza A/H1N1 Detection Set for detection of influenza A/H1N1 Abstract Objective To compare two influenza polymerase chain reaction (PCR) methods. Methods A total of 749 suspected MERS-CoV patients presenting at Johns Hopkins Aramco Healthcare, Saudi Arabia, each submitted a clinical sample for influenza A reflex testing using the on-site Cepheid® Xpert Flu assay and at the Ministry of Health laboratory by the Roche PCR assay. Results There was 92.12% overall agreement between the two methods. Specificity of the Cepheid® Xpert Flu was 95.8% for H1N1 and 94.4% for total influenza A. Cepheid® Xpert Flu sensitivity for influenza A was 100% for younger patients (0–19-year age group) but significantly lower both for older patients (68.2% for 60–79-year and 50% for ≥80-year age groups) and overall for males compared to females (72.6% and 94.0%, respectively). Conclusions Specificity of the Cepheid® Xpert Flu test was high; however, sensitivity for total influenza A was lower particularly in males and older patients.

negative: Risk perception in Northeast Asia Multi-country surveys of the public’s perception of risk using the same questionnaire were sequentially implemented from April to December 2006 in Japan, China, and South Korea. Statistical analyses, such as traditional mean tests, rank order tests, two-step cluster analysis, and principal component analysis were used to analyze the survey data. The results revealed that Chinese tend to be more tolerant of risk than Japanese and South Koreans. In all three countries, the threats of global warming, cancer, traffic accidents, and fire were perceived as higher-order risks, while infectious diseases and threats from high technology were perceived as lower-order risks. Looking across the entire multi-country sample, we found that Chinese participants perceived greater risk in typhoons, SARS, and drugs; Japanese saw greater risk from gas explosions and potential threats coming over the Internet; while people in all three countries identified earthquakes as a primary risk. These differences in risk perception reflect the natural and socioeconomic conditions in the three countries. Although the study did not emphasize differences in risk perception within countries based on demographic factors such as education, age, and gender, we found that differences based on education and age tended to be greater in China and South Korea than in Japan. We also found that men perceived greater risks than women in China and South Korea, while in Japan it was the opposite with women perceiving greater risks. A comparison of these results with previous studies reveals a bias in past studies toward student samples and indicates the need for more representative samples in multi-country surveys.

negative: COVID-19 Pandemia and Public and Global Mental Health from the Perspective of Global Health Securit The Coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China and has spread all over the world and has caused huge threats to health and lives. It has affected different frontiers of lives and induced many psychiatric individual and collective problems such as panic, anxiety, depression, post-traumatic stress disorders, suspiciousness, infodemia, cacophony, xenophobia, racisms, etc. The COVID-19 outbreak has induced public and global mental health crisis as well as a huge psycho-social experiment. Psychiatry and other mental health sciences can play very useful role in supporting the well-being of COVID-19 patients and their families, healthcare personnel and the society. For successful fighting with present and future pandemics we have to learn more about psychiatric and psychological aspects of COVID-19 from the perspectives of public and global mental health.

negative: Pandemic and Bank Lending: Evidence from the 2009 H1N1 Pandemic This paper empirically analyzes the impact of pandemic on the contracting of bank loans. Using data on syndicated loans during the season of H1N1 Swine Flu, we find that more flu is associated with higher loan spreads and smaller loan size. The adverse impact of pandemic was alleviated by the approval of vaccines.

negative: Public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey Objective To assess whether perceptions of the swine flu outbreak predicted changes in behaviour among members of the public in England, Scotland, and Wales. Design Cross sectional telephone survey using random digit dialling. Setting Interviews by telephone between 8 and 12 May. Participants 997 adults aged 18 or more who had heard of swine flu and spoke English. Main outcome measures Recommended change in behaviour (increases in handwashing and surface cleaning or plans made with a “flu friend”) and avoidance behaviours (engaged in one or more of six behaviours such as avoiding large crowds or public transport). Results 37.8% of participants (n=377) reported performing any recommended behaviour change “over the past four days . . . because of swine flu.” 4.9% (n=49) had carried out any avoidance behaviour. Controlling for personal details and anxiety, recommended changes were associated with perceptions that swine flu is severe, that the risk of catching it is high risk, that the outbreak will continue for a long time, that the authorities can be trusted, that good information has been provided, that people can control their risk of catching swine flu, and that specific behaviours are effective in reducing the risk. Being uncertain about the outbreak and believing that the outbreak had been exaggerated were associated with a lower likelihood of change. The strongest predictor of behaviour change was ethnicity, with participants from ethnic minority groups being more likely to make recommended changes (odds ratio 3.2, 95% confidence interval 2.0 to 5.3) and carry out avoidance behaviours (4.1, 2.0 to 8.4). Conclusions The results support efforts to inform the public about specific actions that can reduce the risks from swine flu and to communicate about the government’s plans and resources. Tackling the perception that the outbreak has been “over-hyped” may be difficult but worthwhile. Additional research is required into differing reactions to the outbreak among ethnic groups.

negative: Pneumonia The chapter will begin with an overview of pathological-clinical correlates in pneumonia, and of the principles of diagnosis and treatment that can be broadly applied to all pneumonias. Thereafter, community-acquired pneumonia, hospital-acquired and ventilator-associated pneumonia, and aspiration pneumonia will be considered separately, considering aspects of management specifically relevant to each. The chapter will end by discussing preventive strategies, and with a brief outline of future challenges for the management of pneumonia.

negative: Influenza Virus Infections Abstract Influenza, commonly known as flu, is a contagious, febrile viral disease. Common symptoms are chills, fever, sore throat, coughing, sneezing, muscle pains, headache, myalgia, etc. Influenza viruses (IVs) belonging to orthomyxovirus group are of three types (types A, B, and C). IVs are enveloped, segmented, negative-stranded RNA viruses containing eight distinct RNA segments (types A and B) and seven RNA segments (type C). Only type A viruses exhibit different subtypes. Currently, 18 hemagglutination (HA) subtypes (H1 to H18) and 11 neuraminidase (NA) subtypes (N1 to N11) are known in humans and other warm-blooded animals. Flu outbreaks occur as annual epidemics in fall and winter and infrequently, as worldwide pandemics. Annual epidemics are caused by antigenic drift due to mutations in HA and NA antigens, whereas pandemics are caused by antigenic shift due to genetic reassortment among different subtype viruses. The first pandemic of the twenty-first century, declared by the World Health Organization (WHO) in 2009, was caused by an H1N1 virus, derived from quadruple reassortment among swine, avian, and human IVs. Currently, two types of antiinfluenza drugs, based on either blocking the M2 proton channel (amantadine and rimantadine) or inhibiting NA (oseltamivir or Tamiflu by Roche and zanamivir or Relanza by GlaxoSmithKline) are available. The virus is commonly spread by aerosol droplets and by fingertips. Therefore, washing hands and avoiding contact with infected persons are the first lines of defense. Indoor living and closeness of people in an enclosed environment in winter facilitate virus transmission leading to epidemics. Annual vaccination is the best preventative measure. Currently, two types of vaccines (subunit vaccine by injection and live attenuated vaccine by nasal spray) are available and recommended by WHO and Centers for Disease Control.

negative: Lethal Influenza in Two Related Adults with Inherited GATA2 Deficiency The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-018-0512-0) contains supplementary material, which is available to authorized users.

negative: A Chinese Case of Coronavirus Disease 2019 (COVID-19) Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey Controversy remains over whether the coronavirus disease 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period.

negative: Cross-subtype Immunity against Avian Influenza in Persons Recently Vaccinated for Influenza Avian influenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease. The aim of this study was to evaluate the immune cross-reactivity between human and avian influenza (H5N1) strains in healthy donors vaccinated for seasonal influenza A (H1N1)/(H3N2). A small frequency of CD4 T cells specific for subtype H5N1 was detected in several persons at baseline, and seasonal vaccine administration enhanced the frequency of such reactive CD4 T cells. We also observed that seasonal vaccination is able to raise neutralizing immunity against influenza (H5N1) in a large number of donors. No correlation between influenza-specific CD4 T cells and humoral responses was observed. N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point. These findings highlight the possibility of boosting cross-type cellular and humoral immunity against highly pathogenic avian influenza A virus subtype H5N1 by seasonal influenza vaccination.

negative: Duration of Stay of Patients with Community-Acquired Pneumonia in Influenza Season. OBJECTIVES There is a seasonal variation in the incidence of some infectious diseases. We analyzed the impact of influenza season (IS) on duration of stay (DOS) and some other characteristics of patients with community-acquired pneumonia (CAP). MATERIALS AND METHODS In our retrospective cohort study, we analyzed data of 369 patients with CAP. RESULTS The mean patient age was 65.5±16.69 years, and 267 (72.4%) patients were male. There was no difference between patients with CAP admitted to hospital and intensive care unit during IS and non-influenza season (NIS) with respect to age, mortality, and DOS. There was no difference in leukocyte and neutrophil counts, C-reactive protein level, and erythrocyte sedimentation rate in different seasons. Although most comorbid disease rates were similar, only cancer, especially lung cancer, was more prevalent in NIS. Bilateral CAP confirmed using thorax computed tomography was more frequent in IS. CONCLUSION Although more patients with bilateral pneumonias were hospitalized in IS, DOS was not different between IS and NIS.

negative: Distinguishing Characteristics between Pandemic 2009–2010 Influenza A (H1N1) and Other Viruses in Patients Hospitalized with Respiratory Illness BACKGROUND: Differences in clinical presentation and outcomes among patients infected with pandemic 2009 influenza A H1N1 (pH1N1) compared to other respiratory viruses have not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was performed of all hospitalized patients at the peak of the pH1N1 season in whom a single respiratory virus was detected by a molecular assay targeting 18 viruses/subtypes (RVP, Luminex xTAG). Fifty-two percent (615/1192) of patients from October, 2009 to December, 2009 had a single respiratory virus (291 pH1N1; 207 rhinovirus; 45 RSV A/B; 37 parainfluenza; 27 adenovirus; 6 coronavirus; and 2 metapneumovirus). No seasonal influenza A or B was detected. Individuals with pH1N1, compared to other viruses, were more likely to present with fever (92% & 70%), cough (92% & 86%), sore throat (32% & 16%), nausea (31% & 8%), vomiting (39% & 30%), abdominal pain (14% & 7%), and a lower white blood count (8,500/L & 13,600/L, all p-values<0.05). In patients with cough and gastrointestinal complaints, the presence of subjective fever/chills independently raised the likelihood of pH1N1 (OR 10). Fifty-five percent (336/615) of our cohort received antibacterial agents, 63% (385/615) received oseltamivir, and 41% (252/615) received steroids. The mortality rate of our cohort was 1% (7/615) and was higher in individuals with pH1N1 compared to other viruses (2.1% & 0.3%, respectively; p = 0.04). CONCLUSIONS/SIGNIFICANCE: During the peak pandemic 2009–2010 influenza season in Rhode Island, nearly half of patients admitted with influenza-like symptoms had respiratory viruses other than influenza A. A high proportion of patients were treated with antibiotics and pH1N1 infection had higher mortality compared to other respiratory viruses.

negative: Global Preparedness Against COVID-19: We Must Leverage the Power of Digital Health The coronavirus disease (COVID-19) pandemic has revealed many areas of public health preparedness that are lacking, especially in lower- and middle-income countries. Digital interventions provide many opportunities for strengthening health systems and could be vital resources in the current public health emergency. We provide several use cases for infection control, home-based diagnosis and screening, empowerment through information, public health surveillance and epidemiology, and leveraging crowd-sourced data. A thoughtful, concerted effort—leveraging existing experience and robust enterprise-grade technologies—can have a substantive impact on the immediate and distal consequences of COVID-19.

negative: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms Abstract The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals’ lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.

negative: The contribution of respiratory pathogens to the seasonality of NHS Direct calls Summary Objectives Primary care is thought to bear half the cost of treating infections in the UK. We describe the seasonal variation in NHS Direct respiratory calls (a new source of primary care data) and estimate the contribution of specific respiratory pathogens to this variation. Methods Linear regression models were used to estimate the weekly contribution of specific respiratory pathogens to the volume of NHS Direct respiratory calls (England and Wales, 2002–2004, all ages and 0–4years). Results Annual peaks in NHS Direct cough and difficulty breathing calls occurred in late December, with peaks in ‘cold/flu’ and fever calls occurring between November and April. The main explanatory variables were influenza (estimated to account for 72.5 calls per 100,000/year; 22% of ‘cold/flu’ calls; 15% of cough; and 13% of fever) and Streptococcus pneumoniae (55.5 per 100,000; 33% of ‘cold/flu’ calls; 20% of cough; and 15% of fever (0–4years)). Conclusions It is estimated that respiratory viruses, notably influenza and RSV, are responsible for at least 50% of the seasonal variation in NHS Direct respiratory calls. These results provide estimates of the burden of specific respiratory diseases reported to NHS Direct, and will help interpret syndromic surveillance data used to provide early warning of rises in community morbidity.

negative: Why tocilizumab could be an effective treatment for severe COVID-19? A severe pneumonia-associated respiratory syndrome caused by a new coronavirus was identified in December 2019 (COVID-19), spread rapidly and has become a world-wide public health challenge. About 25% of COVID-19 patients experienced severe complications including acute respiratory distress syndrome (ARDS), and even progressed into an intensive care unit (ICU) admission and died. The exploration for the mortality causes and advancing novel therapeutic development of severe COVID-19 is crucial at the moment. The biopsy samples analysis at autopsy suggested that increased alveolar exudate caused by aberrant host immune response and inflammatory cytokine storm probably impedes alveolar gas exchange and contributes to the high mortality of severe COVID-19 patients. Our research has identified that pathogenic T cells and inflammatory monocytes incite inflammatory storm with large amount of interleukin 6, therefore monoclonal antibody that targets the IL-6 pathways may potentially curb inflammatory storm. Moreover, Tocilizumab treatment that blocking IL-6 receptors showed inspiring clinical results including temperature returned to normal quickly and respiratory function improved. Therefore, we suggest that Tocilizumab is an effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality.

negative: Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern There is scanty knowledge on the actual pandemic potential of this new SARS-like virus It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases;(ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods

negative: Pandemic dynamics of COVID-19 using epidemic stage, instantaneous reproductive number and pathogen genome identity (GENI) score: modeling molecular epidemiology Background: Global spread of COVID-19 created an unprecedented infectious disease crisis that progressed to a pandemic with >180,000 cases in >100 countries. Reproductive number (R) is an outbreak metric estimating the transmission of a pathogen. Initial R values were published based on the early outbreak in China with limited number of cases with whole genome sequencing. Initial comparisons failed to show a direct relationship viral genomic diversity and epidemic severity was not established for SARS-Cov-2. Methods: Each country's COVID-19 outbreak status was classified according to epicurve stage (index, takeoff, exponential, decline). Instantaneous R estimates (Wallinga and Teunis method) with a short and standard serial interval examined asymptomatic spread. Whole genome sequences were used to quantify the pathogen genome identity score that were used to estimate transmission time and epicurve stage. Transmission time was estimated based on evolutionary rate of 2 mutations/month. Findings: The country-specific R revealed variable infection dynamics between and within outbreak stages. Outside China, R estimates revealed propagating epidemics poised to move into the takeoff and exponential stages. Population density and local temperatures had variable relationship to the outbreaks. GENI scores differentiated countries in index stage with cryptic transmission. Integration of incidence data with genome variation directly increases in cases with increased genome variation. Interpretation: R was dynamic for each country and during the outbreak stage. Integrating the outbreak dynamic, dynamic R, and genome variation found a direct association between cases and genome variation. Synergistically, GENI provides an evidence-based transmission metric that can be determined by sequencing the virus from each case. We calculated an instantaneous country-specific R at different stages of outbreaks and formulated a novel metric for infection dynamics using viral genome sequences to capture gaps in untraceable transmission. Integrating epidemiology with genome sequencing allows evidence-based dynamic disease outbreak tracking with predictive evidence.

negative: The Global Impact of the Coronavirus Pandemic The coronavirus pandemic has engulfed the nations of the world for the first five months of 2020 and altered the pace, fabric and nature of our lives. In this overview accompanying the Special Issue of Cytokine & Growth Factor Reviews, we examine some of the many social and scientific issues impacted by SARS-CoV2 – personal lives, economy, scientific communication, the environment. International members of Istituto Pasteur in Rome and INITIATE, the Marie Curie Training Network reflect on the lasting global impact of the coronavirus pandemic.

negative: The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China Abstract The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002–2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

negative: Using a novel rapid viral test to improve triage of emergency department patients with acute respiratory illness during flu season Abstract Background Acute respiratory illnesses (ARI) are mostly viral in etiology and cause significant morbidity and mortality. Point of care PCR (POC-PCR) is a promising new technology for rapid virus identification but utility in the Emergency Department (ED) is not yet defined. Objectives Primarily, to investigate the value of POC-PCR in rapidly identifying RSV and influenza in the setting of ED triage. Additionally, to assess whether rapid knowledge of accurate test results would improve patient management by preventing nosocomial transmission and optimizing the prescription of antimicrobials for ARIs. Study Design A prospective cohort study of consecutive ED patients with ARI symptoms during peak flu season was conducted. Patient nasopharyngeal swabs were collected and tested using a POC-PCR device; physicians and patients were blinded to results. Virus positive and negative groups were compared by ED patient room placement and antimicrobial therapy ordered. Specificity and sensitivity were calculated using laboratory-PCR as the gold standard. Results Of 119 participants, 52.9% were POC-PCR positive - Influenza A (42.9%), RSV (41.3%), influenza B (15.9%). Nearly 70% of virus positive patients were placed rooms shared with non-ARI patients. Antibiotics were prescribed for 27.3% of virus positive patients, and 77.8% of oseltamivir-eligible patients did not receive therapy. POC-PCR was 100% sensitive (95% CI, 80.5–100.0%) and 95.2% specific (95% CI, 76.2–99.9%). Conclusions Rapid POC-PCR for influenza and RSV in ED triage has excellent sensitivity and specificity and the potential to improve social distancing practices through better triage and increase appropriate prescription of antimicrobials.

negative: The Ivory Tower Lost: How College Students Respond Differently than the General Public to the COVID-19 Pandemic Recently, the pandemic of the novel Coronavirus Disease-2019 (COVID-19) has presented governments with ultimate challenges. In the United States, the country with the highest confirmed COVID-19 infection cases, a nationwide social distancing protocol has been implemented by the President. For the first time in a hundred years since the 1918 flu pandemic, the US population is mandated to stay in their households and avoid public contact. As a result, the majority of public venues and services have ceased their operations. Following the closure of the University of Washington on March 7th, more than a thousand colleges and universities in the United States have cancelled in-person classes and campus activities, impacting millions of students. This paper aims to discover the social implications of this unprecedented disruption in our interactive society regarding both the general public and higher education populations by mining people's opinions on social media. We discover several topics embedded in a large number of COVID-19 tweets that represent the most central issues related to the pandemic, which are of great concerns for both college students and the general public. Moreover, we find significant differences between these two groups of Twitter users with respect to the sentiments they expressed towards the COVID-19 issues. To our best knowledge, this is the first social media-based study which focuses on the college student community's demographics and responses to prevalent social issues during a major crisis.

negative: Comparative Seasonal Respiratory Virus Epidemic Timing in Utah Previous studies have found evidence of viral interference between seasonal respiratory viruses. Using laboratory-confirmed data from a Utah-based healthcare provider, Intermountain Health Care, we analyzed the time-specific patterns of respiratory syncytial virus (RSV), influenza A, influenza B, human metapneumovirus, rhinovirus, and enterovirus circulation from 2004 to 2018, using descriptive methods and wavelet analysis (n = 89,462) on a local level. The results showed that RSV virus dynamics in Utah were the most consistent of any of the viruses studied, and that the other seasonal viruses were generally in synchrony with RSV, except for enterovirus (which mostly occurs late summer to early fall) and influenza A and B during pandemic years.

negative: PepMapper: A Collaborative Web Tool for Mapping Epitopes from Affinity-Selected Peptides Epitope mapping from affinity-selected peptides has become popular in epitope prediction, and correspondingly many Web-based tools have been developed in recent years. However, the performance of these tools varies in different circumstances. To address this problem, we employed an ensemble approach to incorporate two popular Web tools, MimoPro and Pep-3D-Search, together for taking advantages offered by both methods so as to give users more options for their specific purposes of epitope-peptide mapping. The combined operation of Union finds as many associated peptides as possible from both methods, which increases sensitivity in finding potential epitopic regions on a given antigen surface. The combined operation of Intersection achieves to some extent the mutual verification by the two methods and hence increases the likelihood of locating the genuine epitopic region on a given antigen in relation to the interacting peptides. The Consistency between Intersection and Union is an indirect sufficient condition to assess the likelihood of successful peptide-epitope mapping. On average from 27 tests, the combined operations of PepMapper outperformed either MimoPro or Pep-3D-Search alone. Therefore, PepMapper is another multipurpose mapping tool for epitope prediction from affinity-selected peptides. The Web server can be freely accessed at: http://informatics.nenu.edu.cn/PepMapper/

negative: Are co-infections with COVID-19 and Influenza low or underreported? An observational study examining current published literature including three new unpublished cases. As the COVID-19 pandemic continues, one major point of uncertainty is the impact this novel pathogen will have during the upcoming 2020-2021 flu season. While the influenza virus is a known contributor to human morbidity and mortality, the question of how a coinfection between COVID-19 and influenza might manifest is of utmost concern. The aim of this study was to review the limited cases of COVID-19/influenza coinfection currently available in the literature, along with cases in the community of El Paso, Texas, to determine whether any patterns of clinical presentation and morbidity emerged. An international review of the literature was conducted. Six published articles describing COVID-19/influenza coinfection were identified, with a total of thirteen patients described therein. Three additional patients were identified from the El Paso, Texas data. The most common presenting symptoms were fever and cough. The most common laboratory findings were elevated C-reactive protein and lymphocytopenia. Thirteen patients presented with viral pneumonia findings on CT, and nine had findings of ground-glass opacity. Finally, complications were reported in six patients, with most common complication being acute respiratory distress syndrome (ARDS). The results of the review indicate that, due to the similarity in presentation between COVID-19 and influenza, further analysis will be required to understand the effects of coinfection on morbidity and mortality. However, the limited number of coinfection cases in the literature indicates that the implementation of COVID-19 control measures may continue to play a role in limiting the spread of these human respiratory pathogens. This article is protected by copyright. All rights reserved.

negative: Genomic Analysis of Influenza A Viruses, including Avian Flu (H5N1) Strains This study was designed to conduct genomic analysis in two steps, such as the overall relative synonymous codon usage (RSCU) analysis of the five virus species in the orthomyxoviridae family, and more intensive pattern analysis of the four subtypes of influenza A virus (H1N1, H2N2, H3N2, and H5N1) which were isolated from human population. All the subtypes were categorized by their isolated regions, including Asia, Europe, and Africa, and most of the synonymous codon usage patterns were analyzed by correspondence analysis (CA). As a result, influenza A virus showed the lowest synonymous codon usage bias among the virus species of the orthomyxoviridae family, and influenza B and influenza C virus were followed, while suggesting that influenza A virus might have an advantage in transmitting across the species barrier due to their low codon usage bias. The ENC values of the host-specific HA and NA genes represented their different HA and NA types very well, and this reveals that each influenza A virus subtype uses different codon usage patterns as well as the amino acid compositions. In NP, PA and PB2 genes, most of the virus subtypes showed similar RSCU patterns except for H5N1 and H3N2 (A/HK/1774/1999) subtypes which were suspected to be transmitted across the species barrier, from avian and porcine species to human beings, respectively. This distinguishable synonymous codon usage patterns in non-human origin viruses might be useful in determining the origin of influenza A viruses in genomic levels as well as the serological tests. In this study, all the process, including extracting sequences from GenBank flat file and calculating codon usage values, was conducted by Java codes, and these bioinformatics-related methods may be useful in predicting the evolutionary patterns of pandemic viruses.

negative: Mathematical model of infection kinetics and its analysis for COVID-19, SARS and MERS Abstract The purpose of this paper is to reveal the spread rules of the three pneumonia: COVID-19, SARS and MERS. We compare the new spread characteristics of COVID-19 with those of SARS and MERS. By considering the growth rate and inhibition constant of infectious diseases, their propagation growth model is established. The parameters of the three coronavirus transmission growth models are obtained by nonlinear fitting. Parametric analysis shows that the growth rate of COVID-19 is about twice that of the SARS and MERS, and the COVID-19 doubling cycle is two to three days, suggesting that the number of COVID-19 patients would double in two to three days without human intervention. The infection inhibition constant in Hubei is two orders of magnitude lower than in other regions, which reasonably explains the situation of the COVID-19 outbreak in Hubei.

negative: Inside China and COVID-19: Questions and answers

negative: Application of three duplex real-time PCR assays for simultaneous detection of human seasonal and avian influenza viruses This study was performed to develop real-time PCR (qPCR) for detection of human seasonal and avian influenza viruses in duplex format. First duplex qPCR detects haemagglutinin (HA) gene of influenza virus A(H1N1)pdm09 and HA gene of influenza virus A(H3N2), the second reaction detects neuraminidase (NA) gene of influenza virus A(H3N2) and NA gene of influenza virus A(H1N1)pdm09 and A(H5N1), and the third reaction detects HA gene of influenza A(H5N1) and nonstructural protein gene of influenza B virus. Primers and probes were designed using multiple alignments of target gene sequences of different reference strains. Assays were optimised for identical thermocycling conditions. Their specificity was confirmed by conventional PCR and monoplex qPCR with nucleic acids isolated from different influenza viruses and other respiratory pathogens. Plasmid constructs with a fragment of specific gene were used to assess sensitivity of the assay. The limit of detection ranged from 27 to 96 cDNA copies/reaction. Clinical specimens (n = 107) have been tested using new assays, immunofluorescence and monoplex qRT-PCR. It has been shown that developed assays have been capable of rapid and accurate simultaneous detection and differentiation of influenza viruses. They are more sensitive than immunofluorescence and at least as sensitive as monoplex qRT-PCR.

negative: COVID-19: what has been learned and to be learned about the novel coronavirus disease The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.

negative: Return of the Coronavirus: 2019-nCoV The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.

negative: Development of an intervention to reduce transmission of respiratory infections and pandemic flu: measuring and predicting hand-washing intentions. This was an exploratory pilot study forming part of a programme of work to develop and trial an effective web-based intervention to reduce the risk of transmission of respiratory infections by promoting hand washing and other preventive behaviours in pandemic and non-pandemic contexts. The main purpose of this study was to confirm that the behavioural determinants we had identified from theory were related as predicted to intentions and to establish the validity of our measures of behavioural intentions. Participants (N = 84) completed a self-report web-delivered questionnaire measuring intentions to engage in hand washing and the hypothesised behavioural determinants of intentions, based on the theory of planned behaviour and protection motivation theory. In a factorial 2 × 2 design, half of the participants were first randomised to receive messages about potential negative consequences of pandemic flu (the "high-threat" condition) and half were assigned to receive "coping" messages describing the rationale and effectiveness of hand washing for reducing the risk of infection. A substantial proportion of variance in intentions was explained by measures of attitudes (instrumental and affective), social norms (descriptive and injunctive), perceived behavioural control (especially, access to hand gel) and perceived risk (in particular, the likelihood of catching pandemic flu). Our measures of intentions were sensitive to between-group differences, and although our design did not permit causal inference (particularly in view of selective dropout among those required to read most web pages), the pattern of differences was in the expected direction, that is, hand-washing intentions tended to be stronger in those receiving the high-threat message and coping messages. This study provided encouraging confirmation that our intervention development was proceeding correctly. Measures of intentions proved sensitive to group differences, and the behavioural determinants included in the study explained a substantial proportion of the variance in intentions. The study also provided useful indications that our high-threat message might increase hand-washing intentions, that providing hand gel might be beneficial and that it would be necessary to actively manage the risk of selective dropout in the intervention group.

negative: Evaluation of a polymerase chain reaction–electrospray ionization time-of-flight mass spectrometry for the detection and subtyping of influenza viruses in respiratory specimens Abstract Background PCR coupled to electrospray ionization mass spectrometry technology (PCR/ESI-TOF-MS) (PLEX-ID system, Abbott Ibis Biosciences) was developed to characterize microbial pathogens. Objectives To evaluate the performance of the PLEX-ID flu detection™ kit for detecting Influenza viruses by comparison with the multiplex RespiFinder® Kit (PathoFinder). Study design Acute-phase respiratory samples (n =293) were analysed for this purpose. A subpopulation of influenza type A positive samples, identified with the RespiFinder® kit (n =64), were subtyped with the RealTime ready Inf A/H1N1 Detection Set® (Roche Molecular Diagnostics) and results were compared to the PLEX-ID Flu Detection™ kit. Results 274 samples gave concordant results (93.5%, p <0.0001): 65 influenza A-positive, 18 influenza B-positive and 191 negative samples. Of these, 7 samples were PLEX-ID positive/RespiFinder® negative (5 influenza A and 2 influenza B) and 12 were PLEX-ID positive/RespiFinder® negative (10 influenza A and 2 influenza B). PLEX-ID showed one sample as an influenza A and B co-infection while the RespiFinder® assay showed it to be influenza A-positive. The sensitivity, specificity, positive and negative predictive values of the PLEX-ID™ system were 87.4%, 96.5%, 92.2% and 94.1% respectively. Thirteen of 19 discordant samples available for retesting were investigated further with the Anyplex™II RV16 Detection kit (Seegene): seven were RespiFinder® concordant, while six were PLEX-ID™ concordant. Subtyping of 61/64 influenza A samples was concordant (95.3%): 55 were H1N1pdm09 and six were non-H1N1pdm09. Three samples gave negative PLEX-ID™ results (one H1N1pdm09 and two non-H1N1pdm09). Conclusions PCR/ESI-TOF-MS technology showed good diagnostic performances to detect and subtype influenza viruses.

negative: Zoonotic Influenza and Human Health—Part 2: Clinical Features, Diagnosis, Treatment, and Prevention Strategies PURPOSE OF REVIEW: Zoonotic influenza viruses are those influenza viruses that cross the animal-human barrier and can cause disease in humans, manifesting from minor respiratory illnesses to multiorgan dysfunction. The increasing incidence of infections caused by these viruses worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. In this second part of a two-part review, we discuss the clinical features, diagnostic modalities, and treatment of zoonotic influenza, and provide an overview of prevention strategies. RECENT FINDINGS: Illnesses caused by novel reassortant avian influenza viruses continue to be detected and described; most recently, a human case of avian influenza A(H7N4) has been described from China. We continue to witness increasing rates of A(H7N9) infections, with the latest (fifth) wave, from late 2016 to 2017, being the largest to date. The case fatality rate for A(H7N9) and A(H5N1) infections among humans is much higher than that of seasonal influenza infections. Since the emergence of the A(H1N1) 2009 pandemic, and subsequently A(H7N9), testing and surveillance for novel influenzas have become more effective. Various newer treatment options, including peramivir, favipiravir (T-705), and DAS181, and human or murine monoclonal antibodies have been evaluated in vitro and in animal models. SUMMARY: Armed with robust diagnostic modalities, antiviral medications, vaccines, and advanced surveillance systems, we are today better prepared to face a new influenza pandemic and to limit the burden of zoonotic influenza than ever before. Sustained efforts and robust research are necessary to efficiently deal with the highly mutagenic zoonotic influenza viruses.

negative: Interactive web-based graphs of novel coronavirus COVID-19 cases and deaths per population by country An accurate grasp of COVID-19 situation is considered highly important. The website we launched provides graphs of COVID-19 cases and deaths per one million population over time including trajectory analysis, and one can easily grasp the COVID-19 trend and adequately compare the situation between countries through this interactive graph system.

negative: Myocardial injury and COVID-19: Possible mechanisms Abstract Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.

negative: Differences in the seasonality of MERS-CoV and influenza in the Middle East

negative: “Differential risk of hospitalization among single virus infections causing influenza‐like illnesses” BACKGROUND: Acute respiratory infections are a major cause of morbidity in children and are often caused by viruses. However, the relative severity of illness associated with different viruses is unclear. The objective of this study was to evaluate the risk of hospitalization from different viruses in children presenting with an influenza‐like illness (ILI). METHODS: Data from children 5 years old or younger participating in an ILI natural history study from April 2010 to March 2014 was analyzed. The adjusted odds ratio for hospitalization was estimated in children with infections caused by respiratory syncytial virus (RSV), metapneumovirus, bocavirus, parainfluenza viruses, rhinovirus/enterovirus, coronavirus, adenovirus, and influenza. RESULTS: A total of 1486 children (408 outpatients and 1078 inpatients) were included in this analysis. At least one virus was detected in 1227 (82.6%) patients. The most frequent viruses detected as single pathogens were RSV (n = 286), rhinovirus/enterovirus (n = 251), parainfluenza viruses (n = 104), and influenza A or B (n = 99). After controlling for potential confounders (age, sex, recruitment site, days from symptom onset to enrollment, and underlying illnesses), children with RSV and metapneumovirus infections showed a greater likelihood of hospitalization than those infected by parainfluenza viruses (OR 2.7 and 1.9, respectively), rhinovirus/enterovirus (OR 3.1 and 2.1, respectively), coronaviruses (OR 4.9 and 3.4, respectively), adenovirus (OR 4.6 and 3.2, respectively), and influenza (OR 6.3 and 4.4, respectively). CONCLUSIONS: Children presenting with ILI caused by RSV and metapneumovirus were at greatest risk for hospitalization, while children with rhinovirus/enterovirus, parainfluenza, coronavirus, adenovirus, and influenza were at lower risk of hospitalization.

negative: Newly identified respiratory viruses associated with acute lower respiratory tract infections in children in Lanzou, China, from 2006 to 2009 Nasopharyngeal aspirates were collected from 813 children <14 years old with acute lower respiratory tract infections in Lanzhou, China, from December 2006 to November 2009. PCR or RT-PCR was used to screen for the presence of 10 respiratory viruses. Viral agents were identified in 73.92% (601/813) of specimens, including RSV in 40.71%, hMPV in 6.15%, IFVA in 7.13%, IFVB in 0.98%, PIV1-3 in 7.87%, HCoV-HKU1 in 2.21%, HCoV-NL63 in 3.81%, HRV in 19.93%, AdV in 7.50% and HBoV in 11.56%. Two or more viruses were detected in 34.44% (280/813) of cases. The newly identified respiratory viruses, HBoV, hMPV, HCoV-HKU1 and HCoV-NL63, accounted for 22.01% of the detected viral pathogens. RSV and HRV were frequently detected in patients with bronchiolitis, and hMPV was frequently associated with pneumonia. HCoV-NL63 was found to be one of the causative agents of acute respiratory wheezing in young children. No seasonal variation was found in the incidence of detection of HCoV-HKU1, HCoV-NL63 or HBoV. This 3-year study demonstrated that viral pathogens play an important role in children with ALRTIs, and more attention should be paid to these newly identified viral agents.

negative: The cutting edge of thoracic anesthesia during the 2019 coronavirus disease (COVID-19) outbreak Coronavirus disease 2019 (COVID-19) has quickly spread globally, causing a real pandemic. In this critical scenario, lung cancer patients scheduled for surgical treatment need to continue to receive optimal care while protecting them from an eventual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Adequate use of personal protective equipment (PPE) during aerosol-generating procedures (AGPs) and a COVID-19 specific intraoperative management are paramount in order to prevent cross infections. New suggestions or improvement of existing contagion control guidance are needed, even in case of non-symptomatic patients, possibly responsible for virus spread.

negative: Similarities and Evolutionary Relationships of COVID-19 and Related Viruses Today, we are all threatened by an unprecedented pandemic: COVID-19. How different is it from other coronaviruses? Will it be attenuated or become more virulent? Which animals may be its original host? In this study, we analyzed 377 publicly available complete genome sequences for the COVID-19 virus, the previously known flu-causing coronaviruses (HCov-229E, HCov-OC43, HCov-NL63 and HCov-HKU1) and the lethal, pathogenic viruses, SARS, MERS, Victoria, Lassa, Yamagata, Ebola, and Dengue. We found strong similarities between the current circulating COVID-19 and SARS and MERS, as well as COVID-19 in rhinolophines and pangolins. On the contrary, COVID-19 shares little similarity with the flu-causing coronaviruses and the other known viruses. Strikingly, we observed divergence of COVID-19 strains isolated from human hosts has steadily increased from December 2019 to March 2020, suggesting COVID-19 is actively evolving in human hosts. From all existing human COVID-19 genome sequences, we calculated the first common model that represents the shared sequences of the human COVID-19 strains, which provides important information for vaccine and antibody development. Geographic and time -course analysis of the evolutionary trees of the human COVID-19 reveals possible evolutional paths among strains from 21 countries. This finding has important implications to the management of COVID-19 and the development of vaccines.

negative: Initial evidence on the relationship between the coronavirus pandemic and crime in the United States The COVID-19 pandemic led to substantial changes in the daily activities of millions of Americans, with many businesses and schools closed, public events cancelled and states introducing stay-at-home orders. This article used police-recorded open crime data to understand how the frequency of common types of crime changed in 16 large cities across the United States in the early months of 2020. Seasonal auto-regressive integrated moving average (SARIMA) models of crime in previous years were used to forecast the expected frequency of crime in 2020 in the absence of the pandemic. The forecasts from these models were then compared to the actual frequency of crime during the early months of the pandemic. There were no significant changes in the frequency of serious assaults in public or (contrary to the concerns of policy makers) any change to the frequency of serious assaults in residences. In some cities, there were reductions in residential burglary but little change in non-residential burglary. Thefts of motor vehicles decreased in some cities while there were diverging patterns of thefts from motor vehicles. These results are used to make suggestions for future research into the relationships between the coronavirus pandemic and different crimes.

negative: Impact of Middle East Respiratory Syndrome coronavirus (MERS‐CoV) on pregnancy and perinatal outcome BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a viral respiratory disease. Most people infected with MERS-CoV develop severe acute respiratory illness. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries. We report the clinical course of MERS-CoV infection in a pregnant woman who acquired the infection during the last trimester. CASE PRESENTATION: The patient is a 33-year-old female working as a critical care nurse. She was 32 weeks pregnant when she presented with respiratory symptoms after direct contact with a MERS-COV patient. Although the patient was in respiratory failure, necessitated mechanical ventilation, and intensive care (ICU) admission, a healthy infant was delivered. The mother recovered. To the best of our knowledge, this is the first reported case of a laboratory-confirmed Middle East Respiratory Syndrome Coronavirus in a pregnant woman. CONCLUSIONS: Middle East Respiratory Syndrome coronavirus (MERS-CoV) known to cause severe acute respiratory illness associated with a high risk of mortality Various factors may have contributed to the successful outcome of this patient such as young age, presentation during the last stages of pregnancy, and possible differences in immune response.

negative: Influenza and rhinovirus infections among health‐care workers Background and objective: Health‐care workers (HCWs) are at higher risk of acquisition and transmission of respiratory virus infections. Nosocomial transmission of influenza has been documented but whether this is so for other respiratory viruses has not been assessed. Methods: Epidemiological, clinical and viral laboratory surveillance was carried out on HCWs presenting with acute respiratory infection in a university hospital. Results: Over a 2‐year period, 203 subjects were recruited: rhinovirus was the most frequently detected virus (37.7% in flu negative samples) and influenza A/B was positive in only 12.3% of subjects. Only 19.7% of HCWs were immunized against influenza. High detection of rhinovirus occurred even during the peak of the influenza season and half of the infected subjects reported an influenza‐like illness. Conclusion: Rhinovirus infection occurred frequently in this study population and probably contributes to influenza misdiagnosis. Educational interventions about different viruses causing respiratory symptoms and an increase in standards of infection control besides influenza immunization among HCWs is needed.

negative: Tracking and visualization of space-time activities for a micro-scale flu transmission study BACKGROUND: Infectious diseases pose increasing threats to public health with increasing population density and more and more sophisticated social networks. While efforts continue in studying the large scale dissemination of contagious diseases, individual-based activity and behaviour study benefits not only disease transmission modelling but also the control, containment, and prevention decision making at the local scale. The potential for using tracking technologies to capture detailed space-time trajectories and model individual behaviour is increasing rapidly, as technological advances enable the manufacture of small, lightweight, highly sensitive, and affordable receivers and the routine use of location-aware devices has become widespread (e.g., smart cellular phones). The use of low-cost tracking devices in medical research has also been proved effective by more and more studies. This study describes the use of tracking devices to collect data of space-time trajectories and the spatiotemporal processing of such data to facilitate micro-scale flu transmission study. We also reports preliminary findings on activity patterns related to chances of influenza infection in a pilot study. METHODS: Specifically, this study employed A-GPS tracking devices to collect data on a university campus. Spatiotemporal processing was conducted for data cleaning and segmentation. Processed data was validated with traditional activity diaries. The A-GPS data set was then used for visual explorations including density surface visualization and connection analysis to examine space-time activity patterns in relation to chances of influenza infection. RESULTS: When compared to diary data, the segmented tracking data demonstrated to be an effective alternative and showed greater accuracies in time as well as the details of routes taken by participants. A comparison of space-time activity patterns between participants who caught seasonal influenza and those who did not revealed interesting patterns. CONCLUSIONS: This study proved that tracking technology an effective technique for obtaining data for micro-scale influenza transmission research. The findings revealed micro-scale transmission hotspots on a university campus and provided insights for local control and prevention strategies.

negative: Environmental factors and seasonal influenza onset in Okayama city, Japan: case-crossover study. Seasonal influenza infection is a major challenge in public health. The term "seasonal influenza" refers to the typical increase in the number of influenza patients in the winter season in temperature zones. However, it is not clear how environmental factors within a single flu season affect influenza infection in a human population. Therefore, we evaluated the effects of temperature and humidity in the 2006-7 flu season on the onset of seasonal influenza using a case-crossover study. We targeted patients who attended one pediatric clinic in Okayama city, Japan and who were diagnosed as being infected with the seasonal influenza virus. Using 2 references (time-stratified and symmetric bidirectional design), we estimated the effects of average temperature and relative humidity from the onset day (lag0) to 10 days before (lag10). The total number of subjects was 419, and their onset days ranged from 26 December 2006 to 30 April 2007. While the onset was significantly associated with lower temperature, relative humidity was not related. In particular, temperatures before the 3-day incubation period had higher-magnitude odds ratios. For example, the odds ratio and 95% confidence interval for average temperature at time lag 8 was 1.12 (1.08-1.17) per 1.0℃ decrease. Low environmental temperature significantly increased the risk of seasonal influenza onset within the 2006-7 winter season.

negative: Corona Epidemic in Indian context: Predictive Mathematical Modelling The novel Coronavirus pathogen Covid-19 is a cause of concern across the world as the human-to-human infection caused by it is spreading at a fast pace. The virus that first manifested in Wuhan, China has travelled across continents. The increase in number of deaths in Italy, Iran, USA, and other countries has alarmed both the developed and developing countries. Scientists are working hard to develop a vaccine against the virus, but until now no breakthrough has been achieved. India, the second most populated country in the world, is working hard in all dimensions to stop the spread of community infection. Health care facilities are being updated; medical and paramedical staffs are getting trained, and many agencies are raising awareness on the issues related to this virus and its transmission. The administration is leaving no stone unturned to prepare the country to mitigate the adverse effects. However, as the number of infected patients, and those getting cured is changing differently in different states everyday it is difficult to predict the spread of the virus and its fate in Indian context. Different states have adopted measures to stop the community spread. Considering the vast size of the country, the population size and other socio-economic conditions of the states, a single uniform policy may not work to contain the disease. In this paper, we discuss a predictive mathematical model that can give us some idea of the fate of the virus, an indicative data and future projections to understand the further course this pandemic can take. The data can be used by the health care agencies, the Government Organizations and the Planning Commission to make suitable arrangements to fight the pandemic. Though the model is preliminary, it can be used at regional level to manage the health care system in the present scenario. The recommendations can be made, and advisories prepared based on the predictive results that can be implemented at regional levels.

negative: Prior and Novel Coronaviruses, COVID-19, and Human Reproduction: What Is Known? Structured Abstract Objective To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. Design Review of English publications in PubMed and Embase to April 6, 2020. Methods Manuscripts were screened for reports including coronavirus, reproduction, including pathophysiology and pregnancy. Intervention(s) None. Main Outcome Measure(s) Reproductive outcomes; effects on gametes; pregnancy outcomes; neonatal complications. Results Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. SARS-CoV-1 may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following COVID-19 infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-CoV-2 adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or MERS, but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. COVID-19 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. Conclusion COVID-19 infection may adversely affect some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.

negative: New threat: 2019 novel Coronavirus infection and infection control perspective in Turkey

negative: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China BACKGROUND: The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small–medium cities and rural areas. OBJECTIVES: To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. METHODS: Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. RESULTS: Of the 2025 children enrolled in the study, 971 (48·0%) were positive for at least one viral pathogen, in which 890 (91·7%) were <4 years of age. The three most prevalent viruses were influenza A (IAV; 35·8%), respiratory syncytial virus (RSV; 30·5%) and human rhinovirus (HRV; 21·5%). Co-infections were found in 302 cases (31·1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in co-infection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. CONCLUSIONS: This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong.

negative: Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020, making it the most lethal pandemic since the Spanish flu of 1918.1, 2 COVID-19 may preferentially infect individuals with cardiovascular conditions, is more severe in subjects with cardiovascular comorbidities, may directly or indirectly affect the heart and may interact with cardiovascular medications.3 In addition, the widespread effects of the pandemic on the global healthcare system affects the routine and emergency cardiac care for patients who are, may be, or are not infected with COVID-19.

negative: Influenza and SARS: the impact of viral pandemics on maritime health. Global travel and transport play a critical role in the spread of infections. We see this clearly in the first two pandemics of the 21st century: SARS and influenza H1N1-2009. Although air travel contributed to dissemination in these two pandemics, the travel restrictions, quarantines, and heightened vigilance which resulted had an impact on maritime health. Seasonal, pandemic, and avian influenza have some important differences with regards to exposure risks, infectivity, and severity. Most of the data for maritime influenza outbreaks focus on seasonal influenza on cruise ships, but influenza among crew members occurs due to close working conditions and is potentially preventable with staff vaccination programs. To date, avian influenza has low human-to-human transmission; infection typically requires close contact with poultry, but presents with severe disease and a high fatality rate. Pandemic (swine) influenza was readily transmitted between people, including young adults, and caused severe illness in high-risk groups including pregnant women, children, and those with co-morbidities and obesity. In contrast, SARS had lower infectivity compared to influenza, and a longer incubation period. These characteristics slowed its propagation enough that outbreak control measures, such as isolation of infected cases and quarantine of exposed but well persons, were effective in terminating this pandemic. No effective vaccine exists for SARS at this time, whereas countries were able to deploy millions of doses of pandemic influenza vaccine within 7 months after the outbreak was first recognized in Mexico. The lack of a protective vaccine and the higher case fatality rate in SARS will mean that stringent quarantine measures may still be required for outbreak control if SARS ever occurs again. Compliance with international health regulations, and the ability to adapt these to maritime health needs, will be important in the shipping industry.

negative: Emerging diseases at the interface of people, domestic animals and wildlife. The role of wildlife in our understanding of highly pathogenic avian influenza.

negative: Seasonal and pandemic influenza during pregnancy and risk of fetal death: A Norwegian registry-based cohort study Previous studies of fetal death with maternal influenza have been inconsistent. We explored the effect of maternal influenza-like illness (ILI) in pregnancy on the risk of fetal death, distinguishing between diagnoses during regular influenza seasons and the 2009/2010 pandemic and between trimesters of ILI. We used birth records from the Medical Birth Registry of Norway to identify fetal deaths after the first trimester in singleton pregnancies (2006–2013). The Norwegian Directorate of Health provided dates of clinical influenza diagnoses by primary-health-care providers, whereas dates of laboratory-confirmed influenza A (H1N1) diagnoses were provided by the Norwegian Surveillance System for Communicable Diseases. We obtained dates and types of influenza vaccinations from the Norwegian Immunisation Registry. Cox proportional-hazards regression models were fitted to estimate hazard ratios (HRs) of fetal death, with associated 95% confidence intervals (CIs), comparing women with and without an ILI diagnosis in pregnancy. There were 2510 fetal deaths among 417,406 eligible pregnancies. ILI during regular seasons was not associated with increased risk of fetal death: adjusted HR = 0.90 (95% CI 0.64–1.27). In contrast, ILI during the pandemic was associated with substantially increased risk of fetal death, with an adjusted HR of 1.75 (95% CI 1.21–2.54). The risk was highest following first-trimester ILI (adjusted HR = 2.28 [95% CI 1.45–3.59]). ILI during the pandemic—but not during regular seasons—was associated with increased risk of fetal death in the second and third trimester. The estimated effect was strongest with ILI in first trimester. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10654-020-00600-z) contains supplementary material, which is available to authorized users.

negative: Infection by rhinovirus: Similarity of clinical signs included in the case definition of influenza IAn/H1N1 INTRODUCTION: Although new influenza virus (IAn/H1N1) infections are mild and indistinguishable from any other seasonal influenza virus infections, there are few data on comparisons of the clinical features of infection with (IAn/H1N1) and with other respiratory viruses. The incidence, clinical aspects and temporal distribution of those respiratory viruses circulating during flu pandemic period were studied. METHODS: Respiratory samples from patients with acute influenza-like symptoms were collected from May 2009 to December 2009. Respiratory viruses were detected by conventional culture methods and genome amplification techniques. RESULTS: Although IAn/H1N1 was the virus most frequently detected, several other respiratory viruses co-circulated with IAn/H1N1 during the pandemic period, especially rhinovirus. The similarity between clinical signs included in the clinical case definition for influenza and those caused by other respiratory viruses, particularly rhinovirus, suggest that a high percentage of viral infections were clinically diagnosed as case of influenza. CONCLUSIONS: Our study offers useful information to face future pandemics caused by influenza virus, indicating that differential diagnoses are required in order to not overestimate the importance of the pandemic.

negative: Self-reported anosmia and dysgeusia as key symptoms of coronavirus disease 2019 OBJECTIVES: To slow down the transmission of coronavirus disease 2019 (COVID-19), it is important to identify specific symptoms for effective screening. While anosmia/hyposmia and dysgeusia/ageusia have been identified as highly prevalent symptoms, there are wide geographic variations, necessitating the regional evaluation of the prevalence of the symptoms. METHODS: A cross-sectional study was performed to evaluate the self-reported symptoms among adults (over 18 years old) who underwent COVID-19 tests at an ambulatory assessment centre. We identified 1,345 patients (102 positive and 1,243 negative) who visited the assessment centre between March 16 and April 15, 2020. We randomly sampled negative patients in a 1:3 ratio. The primary outcome was the prevalence of self-reported anosmia/hyposmia and dysgeusia/ageusia. Logistic regression was performed to evaluate the association between COVID-19 positivity and loss of smell and taste. RESULTS: Fifty-six of 102 (50%) positive patients and 72 of 306 (23.5%) negative patients completed the survey. Anosmia/hyposmia and dysgeusia/ageusia were more prevalent among COVID-19 positive patients (41.1% v. 4.2%, p < 0.001 for smell and 46.4% v. 5.6%, p < 0.001 for taste). Anosmia/hyposmia and dysgeusia/ageusia were independently highly associated with COVID-19 positivity (adjusted odds ratios 14.4 and 11.4 for smell and taste, respectively). CONCLUSION: In this Canadian study, smell and taste loss may be key symptoms of COVID-19. This evidence can be helpful in the clinical diagnosis of COVID-19, particularly settings of limited testing capacity.

negative: Viroporins in the Influenza Virus Influenza is a highly contagious virus that causes seasonal epidemics and unpredictable pandemics. Four influenza virus types have been identified to date: A, B, C and D, with only A–C known to infect humans. Influenza A and B viruses are responsible for seasonal influenza epidemics in humans and are responsible for up to a billion flu infections annually. The M2 protein is present in all influenza types and belongs to the class of viroporins, i.e., small proteins that form ion channels that increase membrane permeability in virus-infected cells. In influenza A and B, AM2 and BM2 are predominantly proton channels, although they also show some permeability to monovalent cations. By contrast, M2 proteins in influenza C and D, CM2 and DM2, appear to be especially selective for chloride ions, with possibly some permeability to protons. These differences point to different biological roles for M2 in types A and B versus C and D, which is also reflected in their sequences. AM2 is by far the best characterized viroporin, where mechanistic details and rationale of its acid activation, proton selectivity, unidirectionality, and relative low conductance are beginning to be understood. The present review summarizes the biochemical and structural aspects of influenza viroporins and discusses the most relevant aspects of function, inhibition, and interaction with the host.

negative: Epidemiology characteristics of respiratory viruses found in children and adults with respiratory tract infections in southern China Summary Background The World Health Organization (WHO) ranks respiratory tract infection (RTI) as the second leading cause of death worldwide for children under 5 years of age. The aim of this work was to evaluate the epidemiology characteristics of respiratory viruses found in children and adults with RTI from July 2009 to June 2012 in southern China. Methods In this work, a total of 14 237 nasopharyngeal swabs (14 237 patients from 25 hospitals) were analyzed, and seven respiratory viruses (influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human metapneumovirus, human coronavirus, human bocavirus) were detected using PCR/RT-PCR from nasopharyngeal swabs. Results The demographic characteristics, viral prevalence, age distribution, seasonal distribution, and pathogen spectrum of the patients with RTIs were analyzed. Co-infection was observed in 483 specimens, but it was more common in male patients, inpatients, children, and young adults. It varied by season, being more prevalent in the spring and summer and less so in the winter. Human coronavirus and human bocavirus were the most common pathogens, tending to occur in co-infection with other respiratory viruses. Conclusions This work adds to our knowledge of the epidemiology characteristics of these seven common respiratory viruses among patients with RTI in southern China. The detection of the specific viral causes of infection provides a useful starting point for an understanding of illness attributable to respiratory infection, and might also provide data relevant to the development of prevention strategies.

negative: Understanding Epidemic Data and Statistics: A case study of COVID-19 The 2019-Novel-Coronavirus (COVID-19) has affected 181 countries and out of about 1197405 confirmed cases (By April 5). Understanding the transmission dynamics of the infection in each country which affected on a daily basis and evaluating the effectiveness of control policies is critical for our further actions. To date, the statistics of COVID-19 reported cases show more than 80 percent of infected had a mild case of disease, while around 14 percent of infected experienced a severe one and about 5 percent are categorized as critical disease victims. Today's report (2020-04-05; daily updates in the prepared website) shows the confirmed cases of COVID-19 in the US, Spain, Italy, and Germany are 308850, 126168, 124632, and 96092; respectively. Calculating the total Case Fatality Rate (CFR) of Italy (2020-04-04), about 13.3% of confirmed cases passed away. Compared to South Korea's rate of 1.8% (7 times lower than Italy) and China's 4% (69% lower than Italy), the CFR of Italy is too high. There are some effective policies that yield significant changes in the trend of cases. The lockdown policy in China, Italy, and Spain (the effect observed after some days), Shutdown of all non-essential companies in Hubei (the effect observed after 5 days), combined policy in South Korea, and reducing working hours in Iran.

negative: VAPiD: a lightweight cross-platform viral annotation pipeline and identification tool to facilitate virus genome submissions to NCBI GenBank BACKGROUND: With sequencing technologies becoming cheaper and easier to use, more groups are able to obtain whole genome sequences of viruses of public health and scientific importance. Submission of genomic data to NCBI GenBank is a requirement prior to publication and plays a critical role in making scientific data publicly available. GenBank currently has automatic prokaryotic and eukaryotic genome annotation pipelines but has no viral annotation pipeline beyond influenza virus. Annotation and submission of viral genome sequence is a non-trivial task, especially for groups that do not routinely interact with GenBank for data submissions. RESULTS: We present Viral Annotation Pipeline and iDentification (VAPiD), a portable and lightweight command-line tool for annotation and GenBank deposition of viral genomes. VAPiD supports annotation of nearly all unsegmented viral genomes. The pipeline has been validated on human immunodeficiency virus, human parainfluenza virus 1–4, human metapneumovirus, human coronaviruses (229E/OC43/NL63/HKU1/SARS/MERS), human enteroviruses/rhinoviruses, measles virus, mumps virus, Hepatitis A-E Virus, Chikungunya virus, dengue virus, and West Nile virus, as well the human polyomaviruses BK/JC/MCV, human adenoviruses, and human papillomaviruses. The program can handle individual or batch submissions of different viruses to GenBank and correctly annotates multiple viruses, including those that contain ribosomal slippage or RNA editing without prior knowledge of the virus to be annotated. VAPiD is programmed in Python and is compatible with Windows, Linux, and Mac OS systems. CONCLUSIONS: We have created a portable, lightweight, user-friendly, internet-enabled, open-source, command-line genome annotation and submission package to facilitate virus genome submissions to NCBI GenBank. Instructions for downloading and installing VAPiD can be found at https://github.com/rcs333/VAPiD.

negative: Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses Abstract Several research lines are currently ongoing to address the multitude of facets of the pandemic COVID-19. In line with the One-Health concept, extending the target of the studies to the animals which humans are continuously interacting with may favor a better understanding of the SARS-CoV-2 biology and pathogenetic mechanisms; thus, helping to adopt the most suitable containment measures. The last two decades have already faced severe manifestations of the coronavirus infection in both humans and animals, thus, circulating epitopes from previous outbreaks might confer partial protection from SARS-CoV-2 infections. In the present study, we provide an in-silico survey of the major nucleocapsid protein epitopes and compare them with the homologues of taxonomically-related coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Protein sequence alignment provides evidence of high sequence homology for some of the investigated proteins. Moreover, structural epitope mapping by homology modelling revealed a potential immunogenic value also for specific sequences scoring a lower identity with SARS-CoV-2 nucleocapsid proteins. These evidence provide a molecular structural rationale for a potential role in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies.

negative: The Hypothesis of Testing: Paradoxes arising out of reported coronavirus case-counts Many statisticians, epidemiologists, economists and data scientists have registered serious reservations regarding the reported coronavirus case-counts. Limited testing capacity across the country has been widely identified as a key driver of suppressed coronavirus case-counts. The calls to increase testing capacity are well-justified as they become a more frequent point of discussion in the public sphere. While expanded testing is a laudable goal, selection bias will impact estimates of disease prevalence and the effective reproduction number until the entire population is sampled. Moreover, tests are imperfect as false positive/negative rates interact in complex ways with selection bias. In this paper, we attempt to clarify this interaction. Through simple calculations, we demonstrate pitfalls and paradoxes that can arise when considering case-count data in the presence of selection bias and measurement error. The discussion guides several suggestions on how to improve current case-count reporting.

negative: The matrix segment of the “Spanish flu” virus originated from intragenic recombination between avian and human influenza A viruses The 1918 Spanish flu virus has claimed more than 50 million lives. However, the mechanism of its high pathogenicity remains elusive; and the origin of the virus is controversial. The matrix (M) segment regulates the replication of influenza A virus, thereby affecting its virulence and pathogenicity. This study found that the M segment of the Spanish flu virus is a recombinant chimera originating from avian influenza virus and human influenza virus. The unique mosaic M segment might confer the virus high replication capacity, showing that the recombination might play an important role in inducing high pathogenicity of the virus. In addition, this study also suggested that the NA and NS segments of the virus were generated by reassortment between mammalian and avian viruses. Direct phylogenetic evidence was also provided for its avian origin.

negative: Influenza A☆ Abstract The influenza viruses, which contain single-stranded RNA, are classified into 3 types, A, B, and C and belong to the Orthomyxoviridae family of viruses. Types A and B cause annual epidemics and often pandemics of influenza illness, while type C is a less common disease with fewer symptoms.

negative: A scientometric overview of CORD-19 As the COVID-19 pandemic unfolds, researchers from all disciplines are coming together and contributing their expertise. CORD-19, a dataset of COVID-19 and coronavirus publications, has recently been published alongside calls to help mine the information it contains, and to create tools to search it more effectively. Here, we focus on the delineation of the publications included in CORD-19, and analyse this delineation from a scientometric perspective. We find that CORD-19 contains research not only on COVID-19 and coronaviruses, but on viruses in general. Publications from CORD-19 mostly focus on a few, well-defined areas, including: coronaviruses (primarily SARS, MERS, COVID-19); public health and viral epidemics; the molecular biology of viruses; influenza and other families of viruses; immunology and antivirals; methodology (testing, diagnosing, clinical trials). CORD-19 publications published in 2020, especially focused on topics of pressing relevance (spread, infection, efficacy of counter-measures), are disproportionately popular on social media. While we fully endorse the initiative that led to CORD-19, we also advise to consider its relatively broad content critically.

negative: Multiple Viral Infection Detected from Influenza-Like Illness Cases in Indonesia Influenza is one of the common etiologies of the upper respiratory tract infection (URTI). However, influenza virus only contributes about 20 percent of influenza-like illness patients. The aim of the study is to investigate the other viral etiologies from ILI cases in Indonesia. Of the 334 samples, 266 samples (78%) were positive at least for one virus, including 107 (42%) cases of multiple infections. Influenza virus is the most detected virus. The most frequent combination of viruses identified was adenovirus and human rhinovirus. This recent study demonstrated high detection rate of several respiratory viruses from ILI cases in Indonesia. Further studies to determine the relationship between viruses and clinical features are needed to improve respiratory disease control program.

negative: Novel coronavirus pandemic: A global health threat The world is facing one of its worst public health crises in modern history. Coronavirus 2019 (COVID-19) has shown how fragile our global preparedness for infectious diseases is. The world is a small-connected globe with short travel time between its remote parts. COVID-19 has spread globally and swiftly with major impacts on health, economy, and quality of life of communities. At this point in the time, April 9, 2020, >1,500,000 patients have been infected and >88,000 patients have died worldwide within the last 3 months. The status is evolving and the costly lessons learned over time are increasing. These lessons are global as this virus is. They involve different domains of health sciences including virology, public health, clinical, critical care, and disaster management. This review addresses our current knowledge of COVID-19 pandemic from the basic virology and transmission, through prevention, infection control, clinical management, and finally disaster management including the recovery period. This review has a multidisciplinary approach, which is needed at this time. After this difficult period passes, we have to carry the lessons we learned for the future so that we can be better prepared. One thing that has clearly emerged from this ongoing crisis is that infectious diseases have no borders and we have to work together, using the one world, one health approach, if we are to minimize the enormous impact such pandemics can cause.

negative: COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.

negative: Virological and Epidemiological Situation in the Influenza Epidemic Seasons 2016/2017 and 2017/2018 in Poland The World Health Organization estimates that influenza virus infects 3–5 million people worldwide every year, of whom 290,000 to 650,000 die. In the 2016/2017 epidemic season in Poland, the incidence of influenza was 1,692 per 100,000 population. The influenza A virus, subtype A/H3N2/, was the predominant one in that season. However, in the most recent 2017/2018 epidemic season, the incidence exceeded 1,782 per 100,000 already by August of 2018. In this season, influenza B virus predominated, while the A/H1N1/pdm09 strain was most frequent among the influenza A subtypes. The peak incidence, based on the number of clinical specimens tested, was in weeks 4–5 of 2017 and week 8 of 2018 in the 2016/2017 and 2017/2018 epidemic seasons, respectively. As of the 2017/2018 season, a quadrivalent vaccine, consisting of two antigens of influenza A subtypes and another two of influenza B virus, was available in Poland. Nonetheless, the vaccination rate remained at one of the lowest level in Europe, fluctuating between 3% and 4% of the general Polish population.

negative: Transmission potential of the novel coronavirus (COVID-19) onboard the diamond Princess Cruises Ship, 2020 An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January–February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ~11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1–7). Our findings suggest that R(t) decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of R(t) reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.

negative: The utility of preemptive mass influenza vaccination in controlling a sars outbreak during flu season. During flu season, respiratory infections can cause non-specific influenza-like-illnesses (ILIs) in up to one-half of the general population. If a future SARS outbreak were to coincide with flu season, it would become exceptionally difficult to distinguish SARS rapidly and accurately from other ILIs, given the non-specific clinical presentation of SARS and the current lack of a widely available, rapid, diagnostic test. We construct a deterministic compartmental model to examine the potential impact of preemptive mass influenza vaccination on SARS containment during a hypothetical SARS outbreak coinciding with a peak flu season. Our model was developed based upon the events of the 2003 SARS outbreak in Toronto, Canada. The relationship of different vaccination rates for influenza and the corresponding required quarantine rates for individuals who are exposed to SARS was analyzed and simulated under different assumptions. The study revealed that a campaign of mass influenza vaccination prior to the onset of flu season could aid the containment of a future SARS outbreak by decreasing the total number of persons with ILIs presenting to the health-care system, and consequently decreasing nosocomial transmission of SARS in persons under investigation for the disease.

negative: Comparison of SARS-CoV-2 Exit Strategies Building Blocks We consider and compare various exit strategy building blocks and key measures to mitigate the current SARS-CoV-2 pandemic, some already proposed as well as improvements we suggest. Our comparison is based on a computerized simulation integrating accumulated SARS-CoV-2 epidemiological knowledge. Our results stress the importance of immediate on-symptom isolation of suspected cases and household members, and the beneficial effects of prompt testing capacity. Our findings expose significant epidemic-suppression differences among strategies with seemingly similar economic cost stressing the importance of not just the portion of population and business that is released, but also the pattern. The most effective building blocks are the ones that integrate several base strategies - they allow to release large portions of the population while still achieving diminishing viral spread. However, it may come with a price on somewhat more complex schemes. For example, our simulations indicate that dividing the population into two groups completely released except for taking turns on a long weekend (Fri-Tue) self-isolation once every two weeks, while protecting the 5% most sensitive population would reduce R below 1 even if ten percent of the population does not follow it. We further simulate the contrasting approach of a stratified population release in a hope to achieve herd immunity, which for the time being seems inferior to other suggested building blocks. Knowing the tradeoff between building blocks could help optimize exit strategies to be more effective and suitable for a particular area or country, while maximizing human life as well as economic value. Given our results, we believe that pandemic can be controlled within a reasonable amount of time and at a reasonable socio-economic burden.

negative: Clinical, laboratory, and radiological features indicative of novel coronavirus disease (COVID‐19) in emergency departments – a multicentre case‐control study in Hong Kong OBJECTIVES: Little is known about the value of routine clinical assessment in identifying patients with coronavirus disease 2019 (COVID‐19) in the emergency department (ED). We aimed to compare the exposure history, signs and symptoms, laboratory, and radiographic features of ED patients who tested positive and negative for COVID‐19. METHODS: This was a case‐control study in seven EDs in Hong Kong from 20 January to 29 February 2020. Thirty‐seven patients with laboratory‐confirmed COVID‐19 were age‐ and gender‐matched to 111 controls. We compared the groups with univariate analysis and calculated the odds ratio (OR) of having COVID‐19 for each characteristic that was significantly different between the groups with adjustment for age and presumed location of acquiring the infection. RESULTS: There were no significant differences in patient characteristics and reported symptoms between the groups. A positive contact history within 14 days (adjusted OR 37.61, 95% CI 10.86‐130.19), bilateral chest radiograph shadow (adjusted OR 13.19, 95% CI 4.66‐37.35), having prior medical consultation (adjusted OR 7.43, 95% 2.89 ‐19.09), a lower white blood cell count (adjusted OR 1.30, 95% CI 1.11‐1.51), and a lower platelet count (adjusted OR 1.07, 95% CI 1.01‐1.12) were associated with a higher odds of COVID‐19 separately. A higher neutrophil count was associated with a lower odds of COVID‐19 (adjusted OR 0.77, 95% CI 0.65‐0.91). CONCLUSION: This study highlights a number of clinical features that may be useful in identifying high‐risk patients for early testing and isolation while waiting for the test result. Further studies are warranted to verify the findings. This article is protected by copyright. All rights reserved

negative: Abstract of 29th Regional Congress of the ISBT

negative: Epidemiology and Virology of Acute Respiratory Infections During the First Year of Life: A Birth Cohort Study in Vietnam BACKGROUND: Understanding viral etiology and age-specific incidence of acute respiratory infections in infants can help identify risk groups and inform vaccine delivery, but community-based data is lacking from tropical settings. METHODS: One thousand four hundred and seventy-eight infants in urban Ho Chi Minh City and 981 infants in a semi-rural district in southern Vietnam were enrolled at birth and followed to 1 year of age. Acute respiratory infection (ARI) episodes were identified through clinic-based illness surveillance, hospital admissions and self-reports. Nasopharyngeal swabs were collected from infants with respiratory symptoms and tested for 14 respiratory pathogens using multiplex reverse transcription-polymerase chain reaction. RESULTS: Estimated incidence of ARI was 542 and 2691 per 1000 infant-years, and hospitalization rates for ARI were 81 and 138 per 1000 infant-years, in urban and semi-rural cohorts, respectively, from clinic- and hospital-based surveillance. However self-reported ARI episodes were just 1.5-fold higher in the semi-rural versus urban cohort, indicating that part of the urban–rural difference was explained by under-ascertainment in the urban cohort. Incidence was higher in infants ≥6 months of age than <6 months, but this was pathogen-specific. One or more viruses were detected in 53% (urban) and 64% (semi-rural) of samples from outpatients with ARI and in 78% and 66% of samples from hospitalized ARI patients, respectively. The most frequently detected viruses were rhinovirus, respiratory syncytial virus, influenza virus A and bocavirus. ARI-associated hospitalizations were associated with longer stays and more frequent ICU admission than other infections. CONCLUSIONS: ARI is a significant cause of morbidity in Vietnamese infants and influenza virus A is an under-appreciated cause of vaccine-preventable disease and hospitalizations in this tropical setting. Public health strategies to reduce infant ARI incidence and hospitalization rates are needed.

negative: Bird Flu, SARS and Beyond In the politically sensitive year of 1997, Hong Kong experienced an outbreak of avian flu when the deadly H5N1 virus unprecedentedly jumped the species barrier from chickens and infected human beings. Hong Kong decided to slaughter over a million chickens, and the virus was stopped in its tracks. In 2003, Hong Kong was the epicenter of the SARS pandemic, which originated in Guangdong province. The Faculty of Medicine played key roles in both instances, with its Microbiology Department successfully identifying a novel coronavirus as being responsible for SARS. Hong Kong learned from its experience and took action to combat the emergence of new infectious diseases. Such vigilance paid off in 2009, when swine flu swept the world, and in 2013, when a novel avian flu H7N9 emerged in China.

negative: Talking about colds and flu: The lay diagnosis of two common illnesses among older British people This paper reports on a study of the ways in which 54 older people in South Wales (UK) talk about the symptoms and causes of cold and influenza (flu). The study was designed to understand why older people might reject or accept the offer of seasonal flu vaccine, and in the course of the interviews respondents were also asked to express their views about the nature and causes of the two key illnesses. The latter are among the most common infections in human beings. In terms of the biomedical paradigm the common cold is caused by numerous respiratory viruses, whilst flu is caused by the influenza virus. Medical diagnosis is usually made on clinical grounds without laboratory confirmation. Symptoms of flu include sudden onset of fever and cough, and colds are characterized by sneezing, sore throat, and runny nose, but in practice the symptoms often overlap. In this study we examine the degree by which the views of lay people with respect to both diagnosis and epidemiology diverge with that which is evident in biomedical discourse. Our results indicate that whilst most of the identified symptoms are common to lay and professional people, the former integrate symptoms into a markedly different observational frame from the latter. And as far as causation is concerned it is clear that lay people emphasize the role of ‘resistance’ and ‘immunity’ at least as much as ‘infection’ in accounting for the onset of colds and flu. The data are analyzed using novel methods that focus on the co-occurrence of concepts and are displayed as semantic networks. As well as reporting on its findings the authors draw out some implications of the study for social scientific and policy discussions concerning lay diagnosis, lay expertise and the concept of an expert patient.

negative: COVID‐19: How Can Rural Community Pharmacies Respond to the Outbreak?

negative: Non-Hemagglutinating Flaviviruses: Molecular Mechanisms for the Emergence of New Strains via Adaptation to European Ticks Tick-borne encephalitis virus (TBEV) causes human epidemics across Eurasia. Clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined. TBEV is characteristically a hemagglutinating (HA) virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity. However, for the past few years many atypical HA-deficient strains have been isolated from patients and also from the natural European host tick, Ixodes persulcatus. By analysing the sequences of HA-deficient strains we have identified 3 unique amino acid substitutions (D67G, E122G or D277A) in the envelope protein, each of which increases the net charge and hydrophobicity of the virion surface. Therefore, we genetically engineered virus mutants each containing one of these 3 substitutions; they all exhibited HA-deficiency. Unexpectedly, each genetically modified non-HA virus demonstrated increased TBEV reproduction in feeding Ixodes ricinus, not the recognised tick host for these strains. Moreover, virus transmission efficiency between infected and uninfected ticks co-feeding on mice was also intensified by each substitution. Retrospectively, the mutation D67G was identified in viruses isolated from patients with encephalitis. We propose that the emergence of atypical Siberian HA-deficient TBEV strains in Europe is linked to their molecular adaptation to local ticks. This process appears to be driven by the selection of single mutations that change the virion surface thus enhancing receptor/fusion function essential for TBEV entry into the unfamiliar tick species. As the consequence of this adaptive mutagenesis, some of these mutations also appear to enhance the ability of TBEV to cross the human blood-brain barrier, a likely explanation for fatal encephalitis. Future research will reveal if these emerging Siberian TBEV strains continue to disperse westwards across Europe by adaptation to the indigenous tick species and if they are associated with severe forms of TBE.

negative: An Open Call for Influenza Vaccination Pending the New Wave of Covid-19 In their study, Yue et al. reported influenza co-infection among COVID-19 patients as 57.3%. The study included a period of January 12-February 21, 2020 in Wuhan, China. We have recently detected this rate as 0.54% in Turkey. This difference between rates of co-infection can be explained by the seasonality of the influenza virus. Our study included the period of March 10-May 10. Another study from Wuhan, including the period of 28 January-29 February 2020, reported the rate of influenza co-infection among critically ill COVID-19 patients as 49.5%. Zhu et al. reported 2.7% influenza co-infections among COVID-19 patients, in their study from January 22-February 2. Two studies from USA reported low rates of 0.08% in March 16-April 20, and 0.9% in March 3-March 25. Therefore, studies from the influenza season reported very high rates of co-infection. When the COVID-19 came to Europe and America, the influenza season was almost over and thus the co-infection rates are low. A recent research found moderate to strong correlation between higher influenza vaccine uptake in the elderly and lower COVID-19 deaths in Italy. This might be explained by the prevention of influenza co-infection. In elderly, both influenza and COVID-19 have higher rates of mortality. The impact of prevention of influenza in this fragile group is higher. Current influenza-COVID-19 co-infection reports suggest that co-infection rates are as high as 57% when influenza is circulating. Pending the new waves of COVID-19, it is reasonable to recommend influenza vaccination especially for elderly, but most probably, to general population. This article is protected by copyright. All rights reserved.

negative: Prevalence of MERS-CoV Nasal Carriage and Compliance With the Saudi Health Recommendations Among Pilgrims Attending the 2013 Hajj Background. Annually, Saudi Arabia is the host of the Hajj mass gathering. We aimed to determine the Middle East respiratory syndrome coronavirus (MERS-CoV) nasal carriage rate among pilgrims performing the 2013 Hajj and to describe the compliance with the Saudi Ministry of Health vaccine recommendations. Method. Nasopharyngeal samples were collected from 5235 adult pilgrims from 22 countries and screened for MERS-CoV using reverse transcriptase–polymerase chain reaction. Information regarding the participants' age, gender, country of origin, medical conditions, and vaccination history were obtained. Results. The mean age of the screened population was 51.8 years (range, 18–93 years) with a male/female ratio of 1.17:1. MERS-CoV was not detected in any of the samples tested (3210 pre-Hajj and 2025 post-Hajj screening). According to the vaccination documents, all participants had received meningococcal vaccination and the majority of those from at-risk countries were vaccinated against yellow fever and polio. Only 22% of the pilgrims (17.5% of those ≥65 years and 36.3% of diabetics) had flu vaccination, and 4.4% had pneumococcal vaccination. Conclusion. There was no evidence of MERS-CoV nasal carriage among Hajj pilgrims. While rates of compulsory vaccinations uptake were high, uptake of pneumococcal and flu seasonal vaccinations were low, including among the high-risk population.

negative: Global task force for influenza Early detection and rapid response to bird flu, on a global scale, will drastically cut the costs of dealing with a full-blown human flu pandemic, argue Ron Fouchier, Thijs Kuiken, Guus Rimmelzwaan and Albert Osterhaus.

negative: MERS‐CoV, influenza and other respiratory viruses among symptomatic pilgrims during 2014 Hajj season More than two million Muslims visit Makkah, Saudi Arabia, annually to perform the religious rituals of Hajj where the risk of spreading respiratory infections is very common. The aim here was to screen symptomatic pilgrims for Middle East respiratory syndrome coronavirus (MERS‐CoV) and other viral etiologies. Thus, 132 nasopharyngeal samples were collected from pilgrims presenting with acute respiratory symptoms at the healthcare facilities in the holy sites during the 5 days of the 2014 Hajj season. Samples were tested using real‐time reverse transcription polymerase chain reactions and microarray. Demographic data including age, sex, and country of origin were obtained for all participants. While we did not detect MERS‐CoV in any of the samples, several other viruses were detected in 50.8% of the cases. Among the detected viruses, 64.2% of the cases were due to a single‐virus infection and 35.8% were due to the coinfections with up to four viruses. The most common respiratory virus was influenza A, followed by non‐MERS human coronaviruses, rhinoviruses, and influenza B. Together, we found that it was not MERS‐CoV but other respiratory viruses that caused acute respiratory symptoms among pilgrims. The observed high prevalence of influenza viruses underscores the need for more effective surveillance during the Hajj and adoption of stringent vaccination requirements from all pilgrims.

negative: Spatiotemporal distributions of reported cases of the avian influenza H5N1 (bird flu) in Southern China in early 2004. This study investigates spatiotemporal distributions of reported cases of the avian influenza H5N1 (bird flu) in Southern China in early 2004. Forty-nine cases of the avian influenza H5N1 covering a 6-week period (January 19, 2004, through March 9, 2004) were compiled from the Chinese Ministry of Agriculture and the World Health Organization. Geographic information systems (GIS) techniques combined with statistical techniques were used to analyze the spatiotemporal variation of reported cases of avian influenza. Using Oden's direction method, we also explored the spatiotemporal interaction of individual-level avian influenza cases during the study duration. The peak period (temporal clustering) for the epidemiological avian influenza outbreak occurred between the third and fourth weeks. Although we observed a major northeast-southwest distribution of the avian influenza H5N1 cases, there was no significant spatiotemporal association in average "direction of advance" of these cases. The directional finding is very consistent with the major migratory bird routes in East Asia, but owing to weak surveillance and reporting systems in the region, the study findings warrant further evaluation.

negative: Initial Psychological Responses to Swine Flu BACKGROUND: The emergence of influenza A (“swine flu”) in early 2009 led to widespread public concern. However, little research has examined the factors that underlie initial worry about infection and subsequent behavioral responses to such worry. PURPOSE: This study seeks to model some key predictors of worry and behavioral responses in the early stages of the swine flu pandemic (WHO pandemic stage 5). METHOD: A cross-sectional internet questionnaire study (N = 186). RESULTS: Twenty-five percent of respondents rated themselves as worried about being a victim of swine flu, 40% that they were worried of a family member contracting the virus. Twenty percent had bought, or intended to buy, preparatory materials (e.g., face masks), 20% intended to delay or cancel air travel. In a structural equation model, conservation values and family or friends perception of risks predicted worry about infection, while worry correlated with the purchase of preparatory materials, a lesser willingness to travel by public transport, and difficulty in focusing on everyday activities. CONCLUSION: While previous research on pandemic risk perception has focused on cognitive risk judgments, our data suggests that initial “emotional” concerns about infection are also significant predictors of behavioral responses to pandemic threat. Such worry is likely to be influenced by a variety of individual factors, such as personal values, as well as normative pressures. Practitioners can use and expand on such models of pandemic response when tailoring health campaigns to meet newly emergent threats.

negative: Assessing impacts of SARS and Avian Flu on international tourism demand to Asia The purpose of this paper is to investigate the impacts of infectious diseases including Avian Flu and severe acute respiratory syndrome (hereafter SARS) on international tourist arrivals in Asian countries using both single datasets and panel data procedures. An autoregressive moving average model together with an exogenous variables (ARMAX) model are used to estimate the effects of these diseases in each SARS- and Avian Flu-infected country, while a dynamic panel model is adopted to estimate the overall impact on the region of these two diseases. The empirical results from both approaches are consistent and indicate that the numbers of affected cases have a significant impact on SARS-affected countries but not on Avian Flu-affected countries. However, since the potential damage arising from the Avian Flu and subsequent pandemic influenza is much greater than that resulting from the SARS, the need to take the necessary precautions in the event of an outbreak of Avian Flu and pandemic influenza warrants further attention and action. Therefore, the empirical findings of this study could add to the knowledge regarding the relationship between tourism and crisis management, especially in so far as the management of transmissible diseases is concerned.

negative: Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. METHODS: We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (R(t)) at the provincial level. FINDINGS: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33–56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0–14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0–9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8–12·4) and the mean serial interval at 5·1 days (1·3–11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74–1·54) in Shenzhen city of Guangdong province and 1·71 (1·32–2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30. INTERPRETATION: Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. FUNDING: National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020.

negative: [Quarantine Alone or in Combination with Other Public Health Measures to Control COVID-19: A Rapid Review (Review)]. BACKGROUND COVID-19 (coronavirus disease 2019) is a new, rapidly emerging zoonotic infectious disease, that was reported to the World Health Organization for the first time on 31 December 2019. Currently, no effective pharmacological interventions or vaccines are available to treat or prevent COVID-19, therefore nonpharmacological public health measures are more in focus. OBJECTIVES The aim was to assess the effects of quarantine - alone or in combination with other measures - during coronavirus outbreaks. METHODS Because of the current COVID-19 pandemic, WHO commissioned a rapid review. To save time, the method of systematic reviews was slightly and with caution modified. This publication is a summary of the most important aspects of the rapid review, translated into German by members of the WHO Collaborating Centre at the Danube University Krems (Austria). RESULTS Overall, 29 studies were included. Ten modeling studies focused on COVID-19, 4 observational studies and 15 modeling studies focused on SARS and MERS. The modeling studies consistently reported a benefit of the simulated quarantine measures. For example, the models estimated that quarantine of people exposed to confirmed or suspected cases of COVID-19 prevented between 44 and 81% of the cases that would otherwise have happened and 31 to 63% of the deaths, when compared to no such measures. In regard to costs, the earlier the quarantine measures are implemented, the greater the cost savings will be. CONCLUSION Our confidence in the evidence is very limited. This is mainly because the COVID-19 studies based their models on the limited data that have been available in the early weeks of the pandemic and made different assumptions about the virus. The studies of SARS and MERS are not completely generalizable to COVID-19. Despite only having limited evidence, all the studies found quarantine to be important for controlling the spread of severe coronavirus diseases. Looking to the coming months, in order to maintain the best possible balance of measures, decision makers must continue to constantly monitor the outbreak situation and the impact of the measures they implement.

negative: RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions.

negative: Household transmission of COVID-19, Shenzhen, January-February 2020 Coronavirus disease 2019 has led to more than three million cases globally. Since the first family cluster of COVID-19 cases identified in Shenzhen in early January, most of the local transmission occurred within household contacts. Identifying the factors associated with household transmission is of great importance to guide preventive measures.

negative: Noninvasive ventilation in acute respiratory failure due to H1N1 influenza: A word of caution

negative: Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design Traditionally, vaccines have been developed by cultivating infectious agents and isolating the inactivated whole pathogen or some of its purified components. 20 years ago, reverse vaccinology enabled vaccine discovery and design based on information deriving from the sequence of microbial genomes rather than via the growth of pathogens. Today, the high throughput discovery of protective human antibodies, sequencing of the B cell repertoire, and the increasing structural characterization of protective antigens and epitopes provide the molecular and mechanistic understanding to drive the discovery of novel vaccines that were previously impossible. We are entering a “reverse vaccinology 2.0” era.

negative: Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review Please cite this paper as: Boëlle P‐Y et al. (2011) Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review. Influenza and Other Respiratory Viruses 5(5), 306–316. Background The new influenza virus A/H1N1 (2009), identified in mid‐2009, rapidly spread over the world. Estimating the transmissibility of this new virus was a public health priority. Methods We reviewed all studies presenting estimates of the serial interval or generation time and the reproduction number of the A/H1N1 (2009) virus infection. Results Thirteen studies documented the serial interval from household or close‐contact studies, with overall mean 3 days (95% CI: 2·4, 3·6); taking into account tertiary transmission reduced this estimate to 2·6 days. Model‐based estimates were more variable, from 1·9 to 6 days. Twenty‐four studies reported reproduction numbers for community‐based epidemics at the town or country level. The range was 1·2–3·1, with larger estimates reported at the beginning of the pandemic. Accounting for under‐reporting in the early period of the pandemic and limiting variation because of the choice of the generation time interval, the reproduction number was between 1·2 and 2·3 with median 1·5. Discussion The serial interval of A/H1N1 (2009) flu was typically short, with mean value similar to the seasonal flu. The estimates of the reproduction number were more variable. Compared with past influenza pandemics, the median reproduction number was similar (1968) or slightly smaller (1889, 1918, 1957).

negative: Mortality Rate of Infection With COVID-19 in Korea From the Perspective of Underlying Disease On December 31, 2019 the China National Health Commission (NHC) reported that an unknown cause of pneumonia had been detected in Wuhan in Hubei province. On February 12, the disease caused by the novel coronavirus (2019-nCoV) was given a formal name, COVID-19. On January 20, 2020, the first case of COVID-19 was confirmed in Korea. The age-specific death rate was the highest among patients over 70 years of age, with underlying diseases in their circulatory system, such as myocardial infarction, cerebral infraction, arrythmia, and hypertension. Patients with underlying disease who are 70 years of age or older should recognize that there is a high possibility of developing a serious disease in case of viral infection and follow strict precautions.

negative: How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1. SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation "breaks down" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.

negative: No MERS-CoV but positive influenza viruses in returning Hajj pilgrims, China, 2013–2015 BACKGROUND: There is global health concern that the mass movement of pilgrims to and from Mecca annually could contribute to the international spread of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In China, about 11,000 Muslim pilgrims participate in the Hajj gathering in Mecca annually. This is the first report of MERS-CoV and respiratory virus molecular screening of returning pilgrims at points of entry in China from 2013 to 2015. METHODS AND RESULTS: A total of 847 returning Hajj pilgrims participated in this study. The test results indicated that of the travelers, 34 tested positive for influenza A virus, 14 for influenza B virus, 4 for metapneumo virus, 2 for respiratory syncytial virus, and 3 for human coronavirus. There was a significant difference in the rates of positive and negative influenza virus tests between Hajj pilgrims with symptoms and those without. The detection rates of influenza virus were not significantly different among the three years studied, at 5.3, 6.0 and 6.3% for 2013, 2014 and 2015, respectively. DISCUSSION AND CONCLUSION: The MERS-CoV and respiratory viruses detection results at points of entry in China from 2013 to 2015 indicated that there were no MERS-CoV infection but a 5.7% positive influenza viruses in returning Chinese pilgrims.

negative: Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study BACKGROUND: Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. METHODS: Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006–11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. FINDINGS: Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16–22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13–34), suggesting most influenza infections are asymptomatic. 25% (18–35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10–26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. INTERPRETATION: Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. FUNDING: Medical Research Council and the Wellcome Trust.

negative: Swine flu update: bringing home the bacon. In 6 weeks, swine influenza A(H1N1) virus has spread from 10 to 74 countries. Australia has the fifth highest number of cases and the third highest rate of infection among the top five affected nations. People who are hospitalised with or die from this novel virus are more likely to have predisposing risk factors. There is a predilection for younger age groups and sparing of older age groups. This may be a property of influenza A viruses in general rather than being specific to swine influenza A. If unchecked, the sheer number of cases may lead to much higher numbers of deaths and hospitalised patients than would normally be attributed to a standard influenza season. Paradoxically, the low case-fatality rate of the virus raises the question of how best to approach management of this outbreak. It is uncertain how an expected vaccine against the novel virus will be used.

negative: Prospective comparison of RT-PCR/ESI-MS to Prodesse ProFlu Plus and Cepheid GenXpert for the detection of Influenza A and B viruses RT-PCR/ESI-MS has previously demonstrated the capability to detect and identify respiratory viral pathogens in nasopharyngeal swabs. This study expands on previous research by performing a prospective evaluation of RT-PCR/ESI-MS to detect and identify Influenza A and B viruses compared to Prodesse ProFlu Plus and combined ProFlu Plus and Cepheid Xpert Flu. ProFlu Plus was also used as a gold standard for comparison for respiratory syncytial virus detection. Using ProFlu Plus as a gold standard, RT-PCR/ESI-MS had sensitivity and specificity of 82.1% (23/28) and 100% (258/258), respectively, for Influenza A, 100% (16/16) and 99.6% (269/270), respectively for Influenza B, and 88.6% (39/44) and 99.6% (241/242) for any Influenza virus. Using matching results from ProFlu Plus and Xpert Flu as a gold standard, RT-PCR/ESI-MS had 85.2% (23/27) and 100% (259/259) sensitivity and specificity respectively for Influenza A, 100% (14/14) and 99.6% (270/272), respectively for Influenza B virus. Overall, RT-PCR/ESI-MS was not as sensitive as the combined gold standard of ProFlu Plus and Xpert Flu, although it has the capability of detecting other respiratory viruses.

negative: Transmission of corona virus disease 2019 during the incubation period may lead to a quarantine loophole Background: The ongoing outbreak of novel corona virus disease 2019 (COVID-19) in Wuhan, China, is arousing international concern. This study evaluated whether and when the infected but asymptomatic cases during the incubation period could infect others. Methods: We collected data on demographic characteristics, exposure history, and symptom onset day of the confirmed cases, which had been announced by the Chinese local authorities. We evaluated the potential of transmission during the incubation period in 50 infection clusters, including 124 cases. All the secondary cases had a history of contact with their first-generation cases prior to symptom onset. Results: The estimated mean incubation period for COVID-19 was 4.9 days (95% confidence interval [CI], 4.4 to 5.4) days, ranging from 0.8 to 11.1 days (2.5th to 97.5th percentile). The observed mean and standard deviation (SD) of serial interval was 4.1±3.3 days, with the 2.5th and 97.5th percentiles at -1 and 13 days. The infectious curve showed that in 73.0% of the secondary cases, their date of getting infected was before symptom onset of the first-generation cases, particularly in the last three days of the incubation period. Conclusions: The results indicated the transmission of COVID-9 occurs among close contacts during the incubation period, which may lead to a quarantine loophole. Strong and effective countermeasures should be implemented to prevent or mitigate asymptomatic transmission during the incubation period in populations at high risk.

negative: The 2009 H1N1 Pandemic Adds to Our Knowledge of Influenza Pathogenesis This commentary discusses the pathology and pathogenesis of the 2009 H1N1 influenza A pandemic.

negative: High prevalence of common respiratory viruses and no evidence of Middle East Respiratory Syndrome Coronavirus in Hajj pilgrims returning to Ghana, 2013 OBJECTIVE: The Middle East respiratory syndrome coronavirus (MERS‐CoV) emerged in 2012 on the Arabian Peninsula and has caused severe respiratory disease with more than 800 laboratory‐confirmed cases. The return of infected pilgrims to their home countries with a putative spread of MERS‐CoV necessitates further surveillance. METHODS: A cross sectional study of 839 adult African Hajj pilgrims returning to Accra in Ghana, West Africa, was conducted in 2013 to assess the prevalence of respiratory symptoms as well as of MERS‐CoV, human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza A virus (FLU A) infection. RESULTS: Six hundred and fifty‐one (77.6%) pilgrims had respiratory symptoms. Tests were positive for at least one of the viruses other than MERS‐CoV in 179 (21.3%) of all pilgrims, with 22.4% detection in symptomatic vs. 17.6% detection in asymptomatic pilgrims. No MERS‐CoV was detected, although common respiratory viruses were prevalent, with positive findings for HRV in 141 individuals (16.8%), RSV in 43 individuals (5.1%) and FLU A in 11 individuals (1.3%). Results were positive for more than one virus in 16 (1.9%) individuals, including 14 (1.7%) RSV/HRV co‐infections and 2 (0.2%) FLU A/HRV co‐infections. A total 146 (22.4%) of the symptomatic returnees tested positive for at least one respiratory virus compared with 33 (17.6%) of the asymptomatic pilgrims who had at least one detectable virus in their sample. CONCLUSIONS: The prevalence of viral respiratory infections among Hajj pilgrims in both symptomatic and asymptomatic subjects was high. Although it is reassuring that MERS‐CoV was not detected in the tested population, there is a need for active surveillance of Hajj pilgrims.

negative: A Novel Heuristic Global Algorithm to Predict the COVID-19 Pandemic Trend Background Mathematical models are useful tools to predict the course of an epidemic. The present manuscript proposes a heuristic global algorithm for predicting the COVID-19 pandemic trend. Methods The proposed method utilizes a Gaussian-function-based algorithm for estimating how the temporal evolution of the pandemic develops by predicting daily COVID-19 deaths, for up to 10 days, from the day the prediction is made. This dataset, the number of daily deaths in each country or region, encapsulates information about (a) the quality of the health system of each country or region, (b) the age profile of the country s or region s population, and (c) environmental and other conditions. Findings The validity of the proposed heuristic global algorithm has been tested in the case of China (at different temporal stages of the pandemic), a country where the disease trend seems to have run its course. It has been applied to ten countries/states/cities, namely California, Germany, China, Greece, Iran, Lombardia/Italy, New York, Sweden, United Kingdom and USA, for each one of which predictions have been obtained. The method has also been applied to the United States as a whole, as well as to the states of New York and California, in order to investigate how the pandemic is developing in different parts of the same country. Interpretation Based on the predicted findings, the proposed algorithm seems to offer a robust and reliable method for revealing the SARS-CoV-2 temporal dynamics and disease trend, as such, can be a useful tool for the relevant authorities.

negative: Causal empirical estimates suggest COVID-19 transmission rates are highly seasonal Nearly every country is now combating the 2019 novel coronavirus (COVID-19). It has been hypothesized that if COVID-19 exhibits seasonality, changing temperatures in the coming months will shift transmission patterns around the world. Such projections, however, require an estimate of the relationship between COVID-19 and temperature at a global scale, and one that isolates the role of temperature from confounding factors, such as public health capacity. This paper provides the first plausibly causal estimates of the relationship between COVID-19 transmission and local temperature using a global sample comprising of 166,686 confirmed new COVID-19 cases from 134 countries from January 22, 2020 to March 15, 2020. We find robust statistical evidence that a 1°C increase in local temperature reduces transmission by 13% [-21%, -4%, 95%CI]. In contrast, we do not find that specific humidity or precipitation influence transmission. Our statistical approach separates effects of climate variation on COVID-19 transmission from other potentially correlated factors, such as differences in public health responses across countries and heterogeneous population densities. Using constructions of expected seasonal temperatures, we project that changing temperatures between March 2020 and July 2020 will cause COVID-19 transmission to fall by 43% on average for Northern Hemisphere countries and to rise by 71% on average for Southern Hemisphere countries. However, these patterns reverse as the boreal winter approaches, with seasonal temperatures in January 2021 increasing average COVID-19 transmission by 59% relative to March 2020 in northern countries and lowering transmission by 2% in southern countries. These findings suggest that Southern Hemisphere countries should expect greater transmission in the coming months. Moreover, Northern Hemisphere countries face a crucial window of opportunity: if contagion-containing policy interventions can dramatically reduce COVID-19 cases with the aid of the approaching warmer months, it may be possible to avoid a second wave of COVID-19 next winter.

negative: Seasonality of respiratory viruses causing hospitalizations for acute respiratory infections in children in Nha Trang, Vietnam Abstract Background Acute respiratory infections (ARIs) are the most common causes of death in children under 5 years of age. While the etiology of most pneumonia and ARI episodes is undiagnosed, a broad range of ARI-causing viruses circulate widely in South East Asia. However, the patterns and drivers of the seasonal transmission dynamics are largely unknown. Here we identify the seasonal patterns of multiple circulating viruses associated with hospitalizations for ARIs in Nha Trang, Vietnam. Methods Hospital based enhanced surveillance of childhood ARI is ongoing at Khanh Hoa General Hospital in Nha Trang. RT-PCR was performed to detect 13 respiratory viruses in nasopharyngeal samples from enrolled patients. Seasonal patterns of childhood ARI hospital admissions of various viruses were assessed, as well as their association with rainfall, temperature, and dew point. Results Respiratory syncytial virus peaks in the late summer months, and influenza A in April to June. We find significant associations between detection of human parainfluenza 3 and human rhinovirus with the month's mean dew point. Using a cross-wavelet transform we find a significant out-of-phase relationship between human parainfluenza 3 and temperature and dew point. Conclusions Our results are important for understanding the temporal risk associated with circulating pathogens in Southern Central Vietnam. Specifically, our results can inform timing of routing seasonal influenza vaccination and for when observed respiratory illness is likely viral, leading to judicious use of antibiotics in the region.

negative: Prevalence of human respiratory viruses in adults with acute respiratory tract infections in Beijing, 2005–2007 To determine the aetiological role and epidemiological profile of common respiratory viruses in adults with acute respiratory tract infections (ARTIs), a 2-year study was conducted in Beijing, China, from May 2005 to July 2007. Nose and throat swab samples from 5808 ARTI patients were analysed by PCR methods for common respiratory viruses, including influenza viruses (IFVs) A, B, and C, parainfluenza viruses (PIVs) 1–4, enteroviruses (EVs), human rhinoviruses (HRVs), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human coronaviruses (HCoVs) OC43, 229E, NL63, and HKU1, and adenoviruses (ADVs). Viral pathogens were detected in 34.6% of patient samples, and 1.6% of the patients tested positive for more than one virus. IFVs (19.3%) were the dominant agents detected, followed by HRVs (6.5%), PIVs (4.3%), EVs (3.2%), and HCoVs (1.1%). ADVs, RSV and HMPV were also detected (<1%). The viral detection rates differed significantly between infections of the lower and upper respiratory tracts in the sample population: PIVs, the second most commonly detected viral agents in lower acute respiratory tract infections (LRTIs), were more prevalent than in upper acute respiratory tract infections, indicating that the pathogenic role of PIVs in LRTIs should be investigated. Currently, this study is the largest-scale investigation of respiratory virus infections in China with multiple agent detection, providing baseline data for further studies of respiratory virus infections in adults with ARTIs.

negative: Seasonality of respiratory viral identification varies with age and Aboriginality in metropolitan Western Australia. BACKGROUND Viral respiratory infections are a major cause of pediatric illness. It is not known whether seasonality of viruses differs between Aboriginal and non-Aboriginal children of varying ages. METHODS We extracted data on respiratory syncytial virus (RSV), influenza viruses A and B, parainfluenza virus types 1, 2, and 3 and adenovirus identified through cell culture or direct immunofluorescence between 1997 and 2005 from nasopharyngeal or throat specimens at Western Australia's only pediatric hospital. We used harmonic analysis in generalized linear models to examine the variations in seasonality of these viruses with Aboriginality and age. RESULTS A respiratory virus was identified in 32% of 32 741 specimens. RSV (18.6%), influenza virus A (5.1%), and parainfluenza virus 3 (4.0%) were most common. The median age at time of identification was lower in Aboriginal children than non-Aboriginal for all viruses except RSV. Seasonality differed between all viruses and varied with age for RSV, influenza viruses and adenovirus. Influenza viruses A and B activity peaked earlier in Aboriginal than non-Aboriginal children during 1997, 1998, and 2002. CONCLUSIONS All viruses showed distinct seasonality. Variability with age and different seasonal patterns for influenza viruses in Aboriginal children compared with non-Aboriginal children has to be taken into account when identifying target groups and timing for vaccination and other interventions.

negative: Viral Lower Respiratory Tract Infection in the Elderly: A Prospective In-Hospital Study The objective of this prospective study was to evaluate the clinical and laboratory parameters distinguishing viral from nonviral lower respiratory tract infection in elderly patients and to determine the yield of virological diagnostics in elderly patients with lower respiratory tract infection. The study was conducted in a 184-bed geriatric department in a university hospital during 4 winter months. All consecutive elderly persons admitted with a lower respiratory tract infection were included in the study. Clinical and laboratory parameters, a nasopharyngeal swab, and serological results for respiratory viruses were obtained for all participants. Available blood and sputum cultures were analysed. A total of 165 elderly persons (mean age, 82±6.8 years) were hospitalised with a lower respiratory tract infection. Familial flu-like illness (OR, 4.25; 95%CI, 1.4–13), better functionality (OR, 4; 95%CI, 1.3–14.15), and leucocyte count <10(10)/l (OR, 3; 95%CI, 1.3–7.1) were predictive for viral lower respiratory tract infection. Sixty (36.5%) definite diagnoses (positive blood culture, viral culture, or serological test) and seven (4.2%) probable diagnoses (positive sputum culture) were obtained. An early diagnosis (within 72 h) was possible in 38 (23%) and a late diagnosis in 29 (17.6%) participants. A nasopharyngeal swab contributed in 60.5% of the cases to an early diagnosis. Viral culture identified half (22/43) of the lower respiratory tract infections caused by influenza but only one of six lower respiratory tract infections caused by respiratory syncytial virus. In conclusion, a history of flu-like illness in family members and a total leucocyte count within normal limits makes a viral cause more likely in elderly people hospitalised with a lower respiratory tract infection during winter. Viral culture and rapid antigen detection are insensitive in elderly patients hospitalised with a lower respiratory tract infection.

negative: Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins The current outbreak of COVID-19 poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-SARS-CoV-2-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.

negative: Randomized controlled trial of the effect of regular paracetamol on influenza infection BACKGROUND AND OBJECTIVE: Anti‐pyretic treatment is recommended in the management of influenza infection. In animal models anti‐pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection. METHODS: This is a randomized, double‐blind, placebo‐controlled trial of adults aged 18–65 years with influenza‐like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT‐PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5–14 days or time of resolution respectively. The primary outcome variable was area under the curve (AUC) for quantitative PCR log(10) viral load from Baseline to Day 5. RESULTS: A total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days. There were 22 and 24 participants who were influenza PCR‐positive in placebo and in paracetamol groups respectively. Mean (SD) AUC PCR log(10) viral load was 4.40 (0.91) in placebo and 4.64 (0.88) in paracetamol; difference was −0.24, 95% CI: −0.78 to 0.29, P = 0.36. In all participants there were no differences in symptom scores, temperature, time to resolution of illness and health status, with no interaction between randomized treatment and whether influenza was detected by PCR. CONCLUSION: Regular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR‐confirmed influenza. There remains an insufficient evidence base for paracetamol use in influenza infection. Clinical trial registration: ACTRN12611000497909 at the Australian New Zealand Clinical Trials Registry.

negative: Characterization of Viral Agents Causing Acute Respiratory Infection in a San Francisco University Medical Center Clinic during the Influenza Season Background. With use of polymerase chain reaction (PCR) and a centrifugation-enhanced viral culture method, we characterized the viruses causing acute respiratory infection in adults during an influenza season. Methods. During January-March 2002, nasopharyngeal wash specimens from previously healthy adults presenting with respiratory symptoms were evaluated for viral pathogens with centrifugation-enhanced viral culture and PCR. Results The diagnoses in 266 cases included unspecified upper respiratory infection (in 142 [54%] of the cases), acute bronchitis (42 [16%]), sinusitis (23 [9%]), pharyngitis (22 [8%]), and pneumonia (17 [6%]). The use of a shell vial assay and PCR identified a pathogen in 103 (39%) of the patients, including influenza A or B in 54, picornavirus in 28 (including rhinovirus in 24), respiratory syncytial virus (RSV) in 12, human metapneumovirus in 4, human coronavirus OC43 in 2, adenovirus in 2, parainfluenza virus type 1 in 1, and coinfection with influenza and parainfluenza virus type 1 in 2. Conclusion. Our findings demonstrate that, even during the influenza season, rhinovirus and RSV are prevalent and must be considered in the differential diagnosis of adult acute respiratory infection before prescribing antiviral medication. Human coronavirus and human metapneumovirus did not play a substantial role. PCR was an especially useful tool in the identification of influenza and other viral pathogens not easily detected by traditional testing methods.

negative: Seasonal variation of window opening behaviors in two naturally ventilated hospital wards Abstract Natural ventilation enables personal control, and occupant behaviors in window opening play a decisive role on natural ventilation performance, indoor air quality (IAQ), and/or airborne infection risk in a hospital setting. The occupant behaviors differ significantly from different building types with different functions and living habits. Based on a one-year field measurement in two general hospital wards in Nanjing, China, the effects of air quality (i.e. indoor CO2 concentration and outdoor PM2.5 concentration) and the climatic parameters (i.e. indoor/outdoor temperature, relative humidity, and outdoor wind speed, wind direction and rainfall) on window opening/closing behaviors are analyzed. Indoor air temperature or relative humidity is found to be a dominant factor for window opening behaviors. Seasonal differences are observed for the different influences of physical factors. The outdoor temperature is found to be associated with the window opening probability negatively during the cooling season, but positively during the transition and heating seasons. The indoor relative humidity positively affects the window opening probability during the transition season while a negative impact appears during the cooling and heating seasons. Based on the seasonal variation of window opening behaviors, Logistic regression models in different seasons (cooling, transition and heating seasons) are developed to predict the window opening/closing state and are verified to be promisingly adaptable with results of accuracy bigger than 70%.

negative: Typical epidemiology of respiratory virus infections in a Brazilian slum Host population size, density, immune status, age structure, and contact rates are critical elements of virus epidemiology. Slum populations stand out from other settings and may present differences in the epidemiology of acute viral infections. We collected nasopharyngeal specimens from 282 children aged ≤5 years with acute respiratory tract infection (ARI) during 2005 to 2006 in one of the largest Brazilian slums. We conducted real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) for 16 respiratory viruses, nested RT‐PCR‐based typing of rhinoviruses (HRVs), and collected clinical symptoms. Viruses were common causes of respiratory disease; with ≥1 virus being detected in 65.2% of patients. We detected 15 different viruses during 1 year with a predomidnance of HRV (33.0%) and human respiratory syncytial virus (hRSV, 12.1%) infections, and a high rate of viral coinfections (28.3%). We observed seasonality of hRSV, HRV and human coronavirus infections, more severe symptoms in hRSV and influenza virus (FLU) infections and prolonged circulation of seven HRV clusters likely representing distinct serotypes according to genomic sequence distances. Potentially unusual findings included the absence of human metapneumovirus detections and lack of typical FLU seasonal patterns, which may be linked to the population size and density of the slum. Nonetheless, most epidemiological patterns were similar to other studies globally, suggesting surprising similarities of virus‐associated ARI across highly diverse settings and a complex impact of population characteristics on respiratory virus epidemiology.

negative: Pandemic influenza A (H1N1) during winter influenza season in the southern hemisphere Please cite this paper as: Hsieh Ying‐Hen. (2010) Pandemic influenza A (H1N1) during winter influenza season in the southern hemisphere. Influenza and Other Respiratory Viruses 4(4), 187–197. Background Countries in the southern hemisphere experienced sizable epidemics of pandemic influenza H1N1 in their winter season during May–August, 2009. Methods We make use of the Richards model to fit the publicly available epidemic data (confirmed cases, hospitalizations, and deaths) of six southern hemisphere countries (Argentina, Brazil, Chile, Australia, New Zealand, and South Africa) to draw useful conclusions, in terms of its reproduction numbers and outbreak turning points, regarding the new pH1N1 virus in a typical winter influenza season. Results The estimates for the reproduction numbers of these six countries range from a high of 1·53 (95% CI: 1·22, 1·84) for confirmed case data of Brazil to a low of 1·16 (1·09, 1·22) for pH1N1 hospitalizations in Australia. For each country, model fits using confirmed cases, hospitalizations, or deaths data always yield similar estimates for the reproduction number. Moreover, the turning points for these closely related outbreak indicators always follow the correct chronological order, i.e., case–hospitalization–death, whenever two or more of these three indicators are available. Conclusions The results suggest that the winter pH1N1 outbreaks in the southern hemisphere were similar to the earlier spring and later winter outbreaks in North America in its severity and transmissibility, as indicated by the reproduction numbers. Therefore, the current strain has not become more severe or transmissible while circulating around the globe in 2009 as some experts had cautioned. The results will be useful for global preparedness planning of possible tertiary waves of pH1N1 infections in the fall/winter of 2010.

negative: Multivariate Analysis of Factors Affecting COVID-19 Case and Death Rate in U.S. Counties: The Significant Effects of Black Race and Temperature Objectives: Coronavirus disease-19 (COVID-19) has spread rapidly around the world, and many risk factors including patient demographics, social determinants of health, environmental variables, underlying health conditions, and adherence to social distancing have been hypothesized to affect case and death rates. However, little has been done to account for the potential confounding effects of these factors. Using a large multivariate analysis, this study illuminates modulators of COVID-19 incidence and mortality in U.S. counties while controlling for risk factors across multiple domains. Methods: Data on COVID-19 and various risk factors in all U.S. counties was collected from publicly available data sources through April 14, 2020. Counties with at least 50 COVID-19 cases were included in case analyses and those with at least 10 deaths were included in mortality models. The 661 counties meeting inclusion criteria for number of cases were grouped into quartiles and comparisons of risk factors were made using t-tests between the highest and lowest quartiles. Similar comparisons for 217 counties were made for above average and below average deaths/100,000. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of factors that significantly impacted cases and deaths. Results: Univariate analyses demonstrated numerous significant differences between cohorts for both cases and deaths. Risk factors associated with increased cases and/or deaths per 100,000 included increased GDP per capita, decreased social distancing, increased age, increased percent Black, decreased percent Hispanic, decreased percent Asian, decreased health, increased poverty, increased diabetes, increased coronary heart disease, increased physical inactivity, increased alcohol consumption, increased tobacco use, and decreased access to primary care. Multivariate regression analyses demonstrated Black race is a risk factor for worse COVID-19 outcome independent of comorbidities, poverty, access to health care, and other mitigating factors. Lower daily temperatures was also an independent risk factor in case load but not deaths. Conclusions: U.S. counties with a higher proportion of Black residents are associated with increased COVID-19 cases and deaths. However, the various suggested mechanisms, such as socioeconomic and healthcare predispositions, did not appear to drive the effect of race in our model. Counties with higher average daily temperatures are also associated with decreased COVID-19 cases but not deaths. Several theories are posited to explain these findings, including prevalence of vitamin D deficiency. Additional studies are needed to further understand these effects.

negative: Demographic and attitudinal determinants of protective behaviours during a pandemic: A review Purpose. A new strain of H1N1 influenza, also known as swine flu was confirmed in the UK in May 2009 and has spread to over 100 countries around the world causing the World Health Organization to declare a global flu pandemic. The primary objectives of this review are to identify the key demographic and attitudinal determinants of three types of protective behaviour during a pandemic: preventive, avoidant, and management of illness behaviours, in order to describe conceptual frameworks in which to better understand these behaviours and to inform future communications and interventions in the current outbreak of swine flu and subsequent influenza pandemics. Methods. Web of Science and PubMed databases were searched for references to papers on severe acute respiratory syndrome, avian influenza/flu, H5N1, swine influenza/flu, H1N1, and pandemics. Forward searching of the identified references was also carried out. In addition, references were gleaned from an expert panel of the Behaviour and Communications sub‐group of the UK Scientific Pandemic Influenza Advisory Group. Papers were included if they reported associations between demographic factors, attitudes, and a behavioural measure (reported, intended, or actual behaviour). Results. Twenty‐six papers were identified that met the study inclusion criteria. The studies were of variable quality and most lacked an explicit theoretical framework. Most were cross‐sectional in design and therefore not predictive over time. The research shows that there are demographic differences in behaviour: being older, female and more educated, or non‐White, is associated with a higher chance of adopting the behaviours. There is evidence that greater levels of perceived susceptibility to and perceived severity of the diseases and greater belief in the effectiveness of recommended behaviours to protect against the disease are important predictors of behaviour. There is also evidence that greater levels of state anxiety and greater trust in authorities are associated with behaviour. Conclusions. The findings from this review can be broadly explained by theories of health behaviour. However, theoretically driven prospective studies are required to further clarify the relationship between demographic factors, attitudes, and behaviour. The findings suggest that intervention studies and communication strategies should focus on particular demographic groups and on raising levels of perceived threat of the pandemic disease and belief in the effectiveness of measures designed to protect against it.

negative: Forecasting the novel coronavirus COVID-19 What will be the global impact of the novel coronavirus (COVID-19)? Answering this question requires accurate forecasting the spread of confirmed cases as well as analysis of the number of deaths and recoveries. Forecasting, however, requires ample historical data. At the same time, no prediction is certain as the future rarely repeats itself in the same way as the past. Moreover, forecasts are influenced by the reliability of the data, vested interests, and what variables are being predicted. Also, psychological factors play a significant role in how people perceive and react to the danger from the disease and the fear that it may affect them personally. This paper introduces an objective approach to predicting the continuation of the COVID-19 using a simple, but powerful method to do so. Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. The risks are far from symmetric as underestimating its spread like a pandemic and not doing enough to contain it is much more severe than overspending and being over careful when it will not be needed. This paper describes the timeline of a live forecasting exercise with massive potential implications for planning and decision making and provides objective forecasts for the confirmed cases of COVID-19.

negative: H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix® vaccination A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix® vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251–265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.

negative: A Genomic Perspective on the Origin and Emergence of SARS-CoV-2 The ongoing pandemic of a new human coronavirus, SARS-CoV-2, has generated enormous global concern. We and others in China were involved in the initial genome sequencing of the virus. Herein, we describe what genomic data reveal about the emergence SARS-CoV-2 and discuss the gaps in our understanding of its origins.

negative: How health anxiety influences responses to viral outbreaks like COVID-19: What all decision-makers, health authorities, and health care professionals need to know

negative: Worldwide transmission and seasonal variation of pandemic influenza A(H1N1)2009 virus activity during the 2009–2010 pandemic BACKGROUND: Seasonal influenza activity varies with geography and time of year. OBJECTIVE: To describe how pandemic influenza A(H1N1)2009 [A(H1N1)pdm09] activity varied during the 2009–2010 pandemic. METHODS: We analyzed influenza virological data compiled by the World Health Organization from June 2009–August 2010. We calculated weekly proportions of A(H1N1)pdm09‐positive specimens out of all A(H1N1)pdm09‐positive specimens detected during the study period for each country. We compared parameters of pandemic activity (e.g., peak A[H1N1]pdm09 weekly proportion [peak activity], number of weeks between the 5th and 95th percentiles of A(H1N1)pdm09 cumulative weekly proportion [duration of activity]) between countries in temperate and tropical–subtropical regions. We quantified the proportion of A(H1N1)pdm09 out of all influenza A specimens by country and correlated it with countries' central latitudes. RESULTS: We analyzed data from 80 countries (47 temperate, 33 tropical–subtropical). The median proportion of cases identified during the peak week was higher in temperate (0·12) than in tropical–subtropical (0·09) regions (P < 0·01). The median duration of activity was longer in tropical–subtropical (27 weeks) than in temperate countries (20 weeks) (P < 0·01). In most temperate countries (98%), peak pandemic activity occurred during the fall–winter period. There was a positive correlation between country central latitude and proportion of A(H1N1)pdm09 out of all influenza A specimens (r: 0·76; P < 0·01). CONCLUSIONS: The transmission of A(H1N1)pdm09 exhibited similarities with seasonal influenza transmission in that activity varied between temperate and tropical–subtropical countries and by time of year. Our findings suggest the potential utility of accounting for these factors during future pandemic planning.

negative: Seeding COVID-19 across sub-Saharan Africa: an analysis of reported importation events across 40 countries Background: The first case of COVID-19 in sub-Saharan Africa (SSA) was reported by Nigeria on February 27, 2020. While case counts in the entire region remain considerably less than those being reported by individual countries in Europe, Asia, and the Americas, SSA countries remain vulnerable to significant COVID morbidity and mortality due to systemic healthcare weaknesses, less financial resources and infrastructure to address the new crisis, and untreated comorbidities. Variation in preparedness and response capacity as well as in data availability has raised concerns about undetected transmission events. Methods: Confirmed cases reported by SSA countries were line-listed to capture epidemiological details related to early transmission events into and within countries. Data were retrieved from publicly available sources, including institutional websites, situation reports, press releases, and social media accounts, with supplementary details obtained from news articles. A data availability score was calculated for each imported case in terms of how many indicators (sex, age, travel history, date of arrival in country, reporting date of confirmation, and how detected) could be identified. We assessed the relationship between time to first importation and overall Global Health Security Index (GHSI) using Cox regression. K-means clustering grouped countries according to healthcare capacity and health and demographic risk factors. Results: A total of 2417 confirmed cases of COVID-19 were reported by 40 countries in sub-Saharan Africa during the 30 days after the first known introduction to the region. Out of the 876 cases for which information was publicly available, 677 (77.3%) were considered importation events. At the regional level, imported cases tended to be male (67.3%), were a median 43.0 years old (Range: 6 weeks - 88 years), and most frequently had recent travel history from Europe (43.3%). The median time to reporting an introduction was 19 days; a country's time to report its first importation was not related to GHSI. Mean data availability scores were lowest for countries that had, on average, the highest case fatality rates, lowest healthcare capacity, and highest probability of premature death due to non-communicable diseases. Conclusion: Countries with systemic, demographic, and pre-existing health vulnerabilities to severe COVID-related morbidity and mortality are less likely to report any cases or are reporting with limited public availability of information. Reporting of information on COVID detection and response efforts, as well as on trends in non-COVID illness and care-seeking behavior, is critical to assessing direct and indirect consequences and capacity needs in resource-constrained settings. Such assessments aid in the ability to make data-driven decisions about interventions, country priorities, and risk assessment.

negative: H1N1 influenza: critical care aspects. During the Northern Hemisphere spring of 2009, a novel H1N1 influenza A virus emerged in Mexico, causing widespread human infection and acute critical respiratory illness. The 2009 H1N1 virus spread initially to the United States and Canada, with subsequent rapid global dissemination, leading the World Health Organization (WHO) to declare "a public health emergency of international concern" in April 2009, and upgrading the viral threat to pandemic status in June 2009. Despite initial fears, the severity of the 2009 H1N1 pandemic overall did not differ significantly from that of seasonal influenza. However, the demographics of those at risk of severe illness did differ (affecting children and young adults, rather than the very young and the very old). The 2009 H1N1 pandemic led to rapid implementation of health care initiatives, including the provision of critical care services, to limit the effect of the influenza outbreak on the community. This review focuses on the critical care response to the H1N1 pandemic and examines whether the implementation of critical care services as planned a priori matched the reality of the clinical workload and the patient burden that transpired during the 2009 H1N1 influenza pandemic.

negative: 2019 Novel Coronavirus Outbreak: SOS Alert for Dentists. On January 31, 2020, novel coronavirus (nCoV), a zoonotic virus yet to be identified into the taxonomy, created a powerful ripple through mankind that the World Health Organization has declared a global health emergency.1 This is definitely not the first time that an alarm has been rung by this family of viruses. Epidemic impact of severe acute respiratory syndrome (SARS) due to SARS CoV and Middle East respiratory syndrome (MERS) by MERS CoV has engraved their place in the scientific literature.2 In general, CoV is known to cause respiratory diseases in humans and accounts for one-third of common cold infections.3 The current outbreak by 2019 nCoV in the Chinese city of Wuhan began in December 2019, has infected nearly 102,188 with 3,491 deaths reported as of March 7, 2020, and has spread to nearly 92 countries.1,4 An assumed incubation period between 2 and 14 days, with flu-like symptoms, may progress into severe pneumonia or acute respiratory distress syndrome which may be the reason for mortality.5,6.

negative: Fourth meeting of the Eastern Mediterranean Acute Respiratory Infection Surveillance (EMARIS) network and first scientific conference on acute respiratory infections in the Eastern Mediterranean Region, 11-14 December, 2017, Amman, Jordan Abstract Influenza causes significant morbidity and mortality worldwide. Owing to its ability to rapidly evolve and spread, the influenza virus is of global public health importance. Information on the burden, seasonality and risk factors of influenza in countries of the World Health Organization Eastern Mediterranean Region is emerging because of collaborative efforts between countries, WHO and its partners over the past 10years. The fourth meeting of the Eastern Mediterranean Acute Respiratory Infection Surveillance network was held in Amman, Jordan on 11–14 December 2017. The meeting reviewed the progress and achievements reported by the countries in the areas of surveillance of and response to seasonal, zoonotic and pandemic influenza. The first scientific conference on acute respiratory infection in the Eastern Mediterranean Region was held at the same time and 38 abstracts from young researchers across the Region were presented on epidemiological and virological surveillance, outbreak detection and response, influenza at the animal-human interface, use and efficacy of new vaccines to control respiratory diseases and pandemic influenza threats. The meeting identified a number of challenges and ways to improve the quality of the surveillance system for influenza, sustain the system so as to address pandemic threats and use the data generated from the surveillance system to inform decision-making, policies and practices to reduce the burden of influenza-associated illnesses in the Region.

negative: The Role of Phylogenetic Analysis in Clarifying the Infection Source of a COVID-19 Patient

negative: COVID-19: A Socio-economic Perspective AbstractThe recent outbreak of the COVID-19 or the coronavirus flu pandemic in the world threatens to derail the very existence of humankind The planet could only ignore the challenges posed by this flu strain to its peril This analysis seeks to locate the pandemic, its challenges and probable solutions within a socio-economic, political and medical sciences perspective The various dimensions of the viral disease ranging from its impact on human societies, body politic, health and economic realms have been discussed and analysed This perspective could be seen in the context of the ongoing debates on the nature and consequences of the crisis, as also the evolving dynamics of the same The article examines the current situation and also factors in any future changes A number of solutions have been offered for an effective tackling of this deadly disease, keeping in mind the global developments All in all, the crisis must serve as an important experience for the entire civilization and imparts lessons in health, social, political and economic spheres

negative: Is the reporting timeliness gap for avian flu and H1N1 outbreaks in global health surveillance systems associated with country transparency? BACKGROUND: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap. METHODS: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging diseases, from 2003 to the end of June 2009. The timeliness gap was calculated as the difference in days between the report release dates of the matching outbreaks in the WHO and ProMED-mail systems. Civil liberties scores were collected as indicators of the transparency of each country. The Human Development Index and data indicating the density of physicians and nurses were collected to reflect countries’ development and health workforce statuses. Then, logistic regression was performed to determine the correlation between the timeliness gap and civil liberties, human development, and health workforce status, controlling for year. RESULTS: The reporting timeliness gap for avian flu and H1N1 outbreaks significantly decreased after 2003. On average, reports were posted 4.09 (SD = 7.99) days earlier by ProMED-mail than by the WHO. Countries with partly free (OR = 5.77) and free civil liberties scores (OR = 10.57) had significantly higher likelihoods of longer timeliness gaps than non-free countries. Similarly, countries with very high human development status had significantly higher likelihoods of longer timeliness gaps than countries with middle or low human development status (OR = 5.30). However, no association between the timeliness gap and health workforce density was found. CONCLUSION: The study found that the adoption of IHR 2005, which contributed to countries’ awareness of the importance of timely reporting, had a significant impact in improving the reporting timeliness gap. In addition, the greater the civil liberties in a country (e.g., importance of freedom of the media), the longer the timeliness gap.

negative: Beyond Modelling: Understanding Mental Disorders in Online Social Media Mental disorders are a major concern in societies all over the world, and in spite of the improved diagnosis rates of such disorders in recent years, many cases still go undetected. Nowadays, many people are increasingly utilising online social media platforms to share their feelings and moods. Despite the collective efforts in the community to develop models for identifying potential cases of mental disorders, not much work has been done to provide insights that could be used by a predictive system or a health practitioner in the elaboration of a diagnosis. In this paper, we present our research towards better visualising and understanding the factors that characterise and differentiate social media users who are affected by mental disorders from those who are not. Furthermore, we study to which extent various mental disorders, such as depression and anorexia, differ in terms of language use. We conduct different experiments considering various dimensions of language such as vocabulary, psychometric attributes and emotional indicators. Our findings reveal that positive instances of mental disorders show significant differences from control individuals in the way they write and express emotions in social media. However, there are not quantifiable differences that could be used to distinguish one mental disorder from each other.

negative: Syndromic surveillance insights from a symptom assessment app before and during COVID-19 measures in Germany and the United Kingdom: results from repeated cross-sectional analyses Background: Unprecedented lockdown measures have been introduced in countries across the world to mitigate the spread and consequences of COVID-19. While attention has focused on the effects of these measures on epidemiological indicators relating directly to the infection, there is increased recognition of their broader health implications. However, assessing these implications in real time is a challenge, due to limitations of existing syndromic surveillance data and tools. Objective: To explore the added value of mobile phone app-based symptom assessment tools as real time health insight providers to inform public health policy makers. Methods: A comparative and descriptive analysis of the proportion of all self-reported symptoms entered by users during an Ada assessment in Germany and the United Kingdom (UK) was conducted between two periods: before and after the implementation of Phase One COVID-19 measures. Additional analyses were performed to explore the association between symptom trends and seasonality, and symptom trends and weather. Differences in the proportion of unique symptoms between the periods were analyzed using Pearson's Chi-squared test and reported as Log2 Fold Changes (Log2 FC). Results: Between 48,300-54,900 symptomatic users reported 140,500-170,400 symptoms during the Baseline and Measures periods in Germany. Between 34,200-37,400 symptomatic users in the UK reported 112,100-131,900 symptoms during the Baseline and Measures periods. The majority of symptomatic users were female (Germany 68,600/103,200, 66.52%; UK 51,200/71,600, 72.74%). The majority (Germany 68,500/100,000, 68.45%; UK 50,900/68,800, 73.91%) were aged between 10 and 29 years, and about a quarter (Germany 26,200/100,000, 26.15%; UK 14,900/68,800, 21.65%) were between 30-59 years. 103 symptoms were reported either more or less frequently (with statistically significant differences) during the Measures as compared to the Baseline period, and 34 of these were found in both countries. The following mental health symptoms (Log2 FC, P-value) were reported less often during the Measures period: inability to manage constant stress and demands at work (-1.07, P<.001), memory difficulty (-0.56, P<.001), depressed mood (-0.42, P<.001), and impaired concentration (-0.46, P<.001). Diminished sense of taste (2.26, P<.001) and hyposmia (2.20, P<.001) were reported more frequently during the Measures period. None of the 34 symptoms were found to be different between the same dates in 2019. Fourteen of the 34 symptoms had statistically significant associations with weather variables. Conclusions: Symptom assessment apps have an important role to play in facilitating improved understanding of the implications of public health policies such as COVID-19 lockdown measures. Not only do they provide the means to complement and cross-validate hypotheses based on data collected through more traditional channels, they can also generate novel insights through a real-time syndromic surveillance system.

negative: Using web search queries to monitor influenza-like illness: an exploratory retrospective analysis, Netherlands, 2017/18 influenza season BACKGROUND: Despite the early development of Google Flu Trends in 2009, standards for digital epidemiology methods have not been established and research from European countries is scarce. AIM: In this article, we study the use of web search queries to monitor influenza-like illness (ILI) rates in the Netherlands in real time. METHODS: In this retrospective analysis, we simulated the weekly use of a prediction model for estimating the then-current ILI incidence across the 2017/18 influenza season solely based on Google search query data. We used weekly ILI data as reported to The European Surveillance System (TESSY) each week, and we removed the then-last 4 weeks from our dataset. We then fitted a prediction model based on the then-most-recent search query data from Google Trends to fill the 4-week gap (‘Nowcasting’). Lasso regression, in combination with cross-validation, was applied to select predictors and to fit the 52 models, one for each week of the season. RESULTS: The models provided accurate predictions with a mean and maximum absolute error of 1.40 (95% confidence interval: 1.09–1.75) and 6.36 per 10,000 population. The onset, peak and end of the epidemic were predicted with an error of 1, 3 and 2 weeks, respectively. The number of search terms retained as predictors ranged from three to five, with one keyword, ‘griep’ (‘flu’), having the most weight in all models. DISCUSSION: This study demonstrates the feasibility of accurate, real-time ILI incidence predictions in the Netherlands using Google search query data.

negative: Patterns of influenza B circulation in Brazil and its relevance to seasonal vaccine composition Abstract Data on the burden of disease and circulation patterns of influenza B lineages for Brazil are limited. This review aims to describe the pattern of influenza B occurrence in Brazil to have a better understanding of its epidemiology and its relevance when considering seasonal influenza vaccine composition. A review of the data including analysis of international and local surveillance data as well as information from online search of databases using Medical Subject Headings terms in conjunction with screening of abstracts from scientific events was performed. Based on international epidemiologic surveillance data, moderate levels of influenza B disease (19%; 2006–2014) were observed. Of these nine years, it was possible to compare data from three years (2007, 2008 and 2013) which have information on the circulating influenza B lineage. Co-circulation of influenza B lineages was observed in all these three influenza seasons, of which, during one season, a high degree of mismatch between the vaccine lineage and the predominant circulating lineage (91.4% [2013]) was observed. Local surveillance data reveal a distinct and dynamic distribution of respiratory viruses over the years. Data from published literature and abstracts show that influenza B is a significant cause of disease with an unpredictable circulation pattern and showing trends indicating reemergence of the B/Victoria lineage. The abstracts report notable levels of co-circulation of both influenza B lineages (2000–2013). Mismatch between the Southern hemisphere vaccine and the most prevalent circulating viruses in Brazil were observed in five influenza seasons. The evidence on co-circulation of two influenza B lineages and mismatched seasons in Brazil indicates the benefit of quadrivalent influenza vaccines in conferring broader seasonal influenza protection. Additionally, improving influenza surveillance platforms in Brazil is important for monitoring disease trends and the impact of introducing seasonal influenza vaccination.

negative: Severity of Pneumonia Due to New H1N1 Influenza Virus in Ferrets Is Intermediate between That Due to Seasonal H1N1 Virus and Highly Pathogenic Avian Influenza H5N1 Virus Background. The newly emerged influenza A(H1N1) virus (new H1N1 virus) is causing the first influenza pandemic of this century. Three influenza pandemics of the previous century caused variable mortality, which largely depended on the development of severe pneumonia. However, the ability of the new H1N1 virus to cause pneumonia is poorly understood. Methods. The new H1N1 virus was inoculated intratracheally into ferrets. Its ability to cause pneumonia was compared with that of seasonal influenza H1N1 virus and highly pathogenic avian influenza (HPAI) H5N1 virus by using clinical, virological, and pathological analyses. Results. Our results showed that the new H1N1 virus causes pneumonia in ferrets intermediate in severity between that caused by seasonal H1N1 virus and by HPAI H5N1 virus. The new H1N1 virus replicated well throughout the lower respiratory tract and more extensively than did both seasonal H1N1 virus (which replicated mainly in the bronchi) and HPAI H5N1 virus (which replicated mainly in the alveoli). High loads of new H1N1 virus in lung tissue were associated with diffuse alveolar damage and mortality. Conclusions. The new H1N1 virus may be intrinsically more pathogenic for humans than is seasonal H1N1 virus.

negative: The FilmArray® respiratory panel: an automated, broadly multiplexed molecular test for the rapid and accurate detection of respiratory pathogens The FilmArray Respiratory Panel (RP) (BioFire(™) Diagnostics, Inc., Salt Lake City, UT, USA) is the first multiplex molecular panel cleared by the US FDA for the detection of both bacterial and viral respiratory pathogens in nasopharygeal swabs. The FilmArray RP targets 20 pathogens including 17 viruses and subtypes and three bacteria, and is performed with minimal sample manipulation. The FilmArray RP has a fully automated sample-to-answer workflow with a turn-around-time of approximately 1 h. The reported sensitivity and specificity of the assay ranges from 80 to 100 and 100%, respectively, with the sensitivity for the adenovirus as low as 46%. A new version of the FilmArray RP assay (version 1.7) with improved sensitivity for the adenovirus was released in 2013. The performance characteristics and simplified workflow have allowed its implementation in a wide range of laboratories. The FilmArray RP has changed the diagnostic landscape and will have a significant impact on the care of patients with respiratory tract infection.

negative: Pandemic influenza preparedness: The critical role of the syringe In the face of an almost unprecedented threat of a global pandemic of influenza it is imperative that stockpiling of appropriate drugs and devices begin now. One vital device is an appropriate syringe for delivering vaccine. With the potential for millions to be infected and the vaccine supply severely stretched it is imperative that the syringe used to vaccinate waste as little vaccine as possible and thus allow for a maximum number of persons to be vaccinated. Our study tested seven leading candidate vaccine syringes for dosing accuracy, dose-capacity per vial, medication wastage and a battery of ergonomic features. One device, the Flu+™ syringe, proved superior to the others in all important categories, possibly due to its low dead-space volume and its dosing accuracy. The data suggest that switching to this device from any of the others tested would provide between 2 and 19% additional vaccine doses per vial if the current 10-dose vials are used. Extrapolations from this data suggest that many thousands to millions of additional persons could be vaccinated in mass campaigns. Use of a syringe of this type, and the vaccine savings that would accrue, would likely be important in reducing morbidity and mortality in the event of a pandemic of influenza.

negative: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic Abstract The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and preexisting cardiovascular disease (CVD) have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become host or vectors of virus transmission. We hereby review the peer-reviewed and preprint literature pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.

negative: COVID-19 pandemic perception in adults with celiac disease: an impulse to implement the use of telemedicine: COVID-19 and CeD BACKGROUND: Coronavirus Disease 2019 (COVID-19) causes severe complications and deaths all over the world. COVID-19 also has indirect effects from the lockdown and the possible lack of food. We aimed to evaluate the perception of this in Celiac Disease (CeD) patients who require a lifelong gluten-free diet as a therapy. METHODS: We invited by e-mail CeD adult patients from the University of Salerno (Campania, South Italy) and the University of Padua (Veneto, North Italy) to answer an ad hoc COVID-19 survey. RESULTS: We sent the web survey to 651 email addresses and we received 276 answers (42,4%). CeD patients did not feel more vulnerable because they had CeD (not at all 56.6%)and they did not worry much about the possible shortness of gluten-free food during the epidemic(not at all 48.5%)The most worried were the elderly patients, patients with other comorbidities and females. Finally, CeD patients were happy with remote consultations and explicitly asked to have them. DISCUSSION: The COVID-19 pandemic has impacted a proportion of patients with CeD; in particular, women, elderly patients, patients with other comorbidities. COVID-19, although a challenging experience from the medical and the psychological point of view, has offered an opportunity to practice, on a large-scale, a remote consultation approach for CeD healthcare.

negative: Collateral benefits on other respiratory infections during fighting COVID-19 PURPOSE: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan. METHOD: We collected week-case data of severe influenza, invasive Streptococcus pneumoniae disease and death toll from pneumonia among 25 calendar weeks of the influenza season for four years (2016-2020), which were reported to Taiwan CDC. Trend and slope differences between years were compared. RESULT: A downturn trend of severe influenza, invasive S. pneumoniae disease and the death toll from pneumonia per week in 2019/2020 season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential COVID-19 outbreak in Taiwan. CONCLUSIONS: Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive S. pneumoniae disease activity, and the death toll from pneumonia reported to CDC in Taiwan.

negative: Challenges of global surveillance during an influenza pandemic Summary Surveillance is an essential foundation for monitoring and evaluating any disease process, and is especially critical when new disease agents appear. The H1N1 influenza pandemic of 2009 tested the capacities of countries to detect, assess, notify and report events as required by the 2005 International Health Regulations (IHR). As detailed in the IHR, the World Health Organization drew on official reports from Member States as well as unofficial sources (e.g. media alerts) to quickly report and disseminate information about the appearance of the novel influenza virus. The pre-existing Global Influenza Surveillance Network for virological surveillance also provided crucial information for rapid development of a vaccine and for detection of changes in the virus. However, the pandemic also highlighted a number of shortcomings in global epidemiological surveillance for respiratory disease. These included the lack of standards for reporting illness, risk factor and mortality data, and a mechanism for systematic reporting of epidemiological data. Such measures would have facilitated direct comparison of data between countries and improved timely understanding of the characteristics and impact of the pandemic. This paper describes the surveillance strategies in place before the pandemic and the methods that were used at global level to monitor the pandemic. Enhancements of global surveillance are proposed to improve preparedness and response for similar events in the future.

negative: A guideline for homology modeling of the proteins from newly discovered betacoronavirus, 2019 novel coronavirus (2019‐nCoV) During an outbreak of respiratory diseases including atypical pneumonia in Wuhan, a previously unknown β‐coronavirus was detected in patients. The newly discovered coronavirus is similar to some β‐coronaviruses found in bats but different from previously known SARS‐CoV and MERS‐CoV. High sequence identities and similarities between 2019‐nCoV and SARS‐CoV were found. In this study, we searched the homologous templates of all nonstructural and structural proteins of 2019‐nCoV. Among the nonstructural proteins, the leader protein (nsp1), the papain‐like protease (nsp3), the nsp4, the 3C‐like protease (nsp5), the nsp7, the nsp8, the nsp9, the nsp10, the RNA‐directed RNA polymerase (nsp12), the helicase (nsp13), the guanine‐N7 methyltransferase (nsp14), the uridylate‐specific endoribonuclease (nsp15), the 2'‐O‐methyltransferase (nsp16), and the ORF7a protein could be built on the basis of homology templates. Among the structural proteins, the spike protein (S‐protein), the envelope protein (E‐protein), and the nucleocapsid protein (N‐protein) can be constructed based on the crystal structures of the proteins from SARS‐CoV. It is known that PL‐Pro, 3CL‐Pro, and RdRp are important targets for design antiviral drugs against 2019‐nCoV. And S protein is a critical target candidate for inhibitor screening or vaccine design against 2019‐nCoV because coronavirus replication is initiated by the binding of S protein to cell surface receptors. It is believed that these proteins should be useful for further structure‐based virtual screening and related computer‐aided drug development and vaccine design.

negative: Influenzapandemieplanung: Eine Herausforderung für die Arbeitsmedizin, den öffentlichen Gesundheitsdienst und Unternehmen The term pandemic refers to an international or worldwide outbreak of an infectious disease which is limited in time. Due to their high infectiousness and easy person-to-person transmission, flu viruses repeatedly lead to pandemics (approx. 3 pandemics per century.). In contrast to an epidemic, a pandemic is not restricted to one area. The mortality of an influenza pandemic is greater than the seasonal flu wave, and is not restricted to the classical risk groups: high rates of infection can occur in all age groups, with peaks frequently occurring amongst young adults. The specific virological characteristics of the influenza virus represent a great challenge for the health system. In principle, any influenza virus which has never before — or at least not for a long time — circulated within the population can develop into a pandemic virus. One possible candidate amongst others appears to be the influenza virus A-H5N1. Influenza pandemics usually occur at intervals of 11 to 39 years, and 30 years have now passed since the last pandemic. At the moment, the national and international pandemic plans have in most cases not yet been completely worked out. The co-operation between the individual countries should be intensified, and in Germany in particular, efforts should be made — in view of the different concepts of the individual federal states — to arrive at a uniform action plan. The consequences of a pandemic affect both the economic and the social sphere. Hospitals, practicing doctors and public health services must jointly develop action plans in order to be able to care for large numbers of patients within a very short time. Occupational medical specialists should form a link between health services, companies and doctors and hospitals, and already be developing plans and their communication for the companies under their care.

negative: Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation BACKGROUND: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. METHODS: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. RESULTS: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo. CONCLUSIONS: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.

negative: Etiology and Clinical Characteristics of Influenza-Like Illness (ILI) in Outpatients in Beijing, June 2010 to May 2011 BACKGROUND: Since May 2009, exposure of the population of Beijing, China to pH1N1 has resulted in an increase in respiratory illnesses. Limited information is available on the etiology and clinical characteristics of the influenza-like illness (ILI) that ensued in adults following the pH1N1 pandemic. METHODS: Clinical and epidemiological data of ILI in adults was collected. A total of 279 throat swabs were tested for twelve respiratory viruses using multiplex RT-PCR. Clinical characteristics of influenza A in outpatients versus test-negative patients were compared using Pearson's χ2 and the Mann-Whitney U test. 190 swabs were tested for pH1N1 by virus isolation. Consultation rates for ILI were compared between 2009 and 2010. RESULTS: One or two virus were detected in 29% of the samples. Influenza A virus (FLU-A) accounted for 22.9% (64/279). Other viruses were present at a frequency less than 3.0%. Cough was significantly associated with Influenza A virus infection (χ2, p<0.001). The positive rate of FLU-A was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to 2009. During the 2010–2011 influenza season, the incidence peaked in January 2011 in Beijing and north China. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks, although FLU-A remained the predominant virus for 2010 in Beijing. Symptomatically, cough was associated with FLU-A infection. The positive rate of influenza virus was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to that of 2009.

negative: Deploying Biomolecules as Anti-COVID-19 Agents Severe acute respiratory syndrome coronavirus (SARS-CoV-2) known as COVID-19 has emerged as a major threat to human existence. COVID-19 seems to have undergone adaptive evolution through an intermediate host, most likely bats. The flu leads to severe pneumonia that causes respiratory and multi-organ failure. The absence of any known treatment procedures, drugs, or vaccines has created panic around the World. The need is to develop rapid testing kits, drugs and vaccines. However, these proposals are time-consuming processes. At present social distancing along with previously known traditional medicines can act as quick and short-term alternatives for treating this viral flu.

negative: Cryptic transmission of SARS-CoV-2 in Washington State Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

negative: Age groups and spread of influenza: implications for vaccination strategy BACKGROUND: The unpredictable nature of the potentially devastating impact of 2009 pH1N1 influenza pandemic highlights the need for pandemic preparedness planning, where modeling studies could be most useful for simulations of possible future scenarios. METHODS: A compartmental model with pre-symptomatic and asymptomatic influenza infections is proposed which incorporates age groups as well as intervention measures such as age-specific vaccination, in order to study spread of influenza in a community. RESULTS: We derive the basic reproduction number and other effective reproduction numbers under various intervention measures. For illustration, we make use of the Pneumonia and Influenza (P&I) mortality data and vaccination data of the very young (age 0-2) and the very old (age >64) during 2004-2005 Taiwan winter influenza season to fit our model and to compute the relevant reproduction numbers. The reproduction number for this winter flu season is estimated to be slightly above one (~1.0001). CONCLUSIONS: Comparatively large errors in fitting the P&I mortality data of the elderly (>64) were observed shortly after winter school closings in January, which may indicate the impact of younger, more active age groups transmitting influenza to other age groups outside of the school settings; in particular, to the elderly in the households. Pre-symptomatic infections seemed to have little effect on the model fit, while asymptomatic infection by asymptomatic infectives has a more pronounced impact on the model fit for the elderly mortality, perhaps indicating a larger role in disease transmission by asymptomatic infection. Simulations indicate that the impact of vaccination on the disease incidence might not be fully revealed in the change (or the lack thereof) in the effective reproduction number with interventions, but could still be substantial. The estimated per contact transmission probability for susceptible elderly is significantly higher than that of any other age group, perhaps highlighting the vulnerability of the elderly due to close contacts with their caretakers from other age groups. The relative impact of targeting the very young and the very old for vaccination was weakened by their relative inactivity, thus giving evidence of the lack of impact of vaccinating these two groups on the overall transmissibility of the disease in the community. This further underscores the need for morbidity-based strategy to prevent elderly mortality.

negative: VIGOR extended to annotate genomes for additional 12 different viruses A gene prediction program, VIGOR (Viral Genome ORF Reader), was developed at J. Craig Venter Institute in 2010 and has been successfully performing gene calling in coronavirus, influenza, rhinovirus and rotavirus for projects at the Genome Sequencing Center for Infectious Diseases. VIGOR uses sequence similarity search against custom protein databases to identify protein coding regions, start and stop codons and other gene features. Ribonucleicacid editing and other features are accurately identified based on sequence similarity and signature residues. VIGOR produces four output files: a gene prediction file, a complementary DNA file, an alignment file, and a gene feature table file. The gene feature table can be used to create GenBank submission. VIGOR takes a single input: viral genomic sequences in FASTA format. VIGOR has been extended to predict genes for 12 viruses: measles virus, mumps virus, rubella virus, respiratory syncytial virus, alphavirus and Venezuelan equine encephalitis virus, norovirus, metapneumovirus, yellow fever virus, Japanese encephalitis virus, parainfluenza virus and Sendai virus. VIGOR accurately detects the complex gene features like ribonucleicacid editing, stop codon leakage and ribosomal shunting. Precisely identifying the mat_peptide cleavage for some viruses is a built-in feature of VIGOR. The gene predictions for these viruses have been evaluated by testing from 27 to 240 genomes from GenBank.

negative: Postdigital Research in the Time of Covid-19 The First 80 Days of Covid-19 The first case of the coronavirus disease, Covid-19, was officially reported from Wuhan, China, on 31 December 2019 (World Health Organization 2020a) The coronavirus disease had initially been compared with an ordinary flu, and Dr Li Wenliang, who raised the alarm in the early days of the outbreak, was investigated by the Chinese police and the Public Security Bureau for ‘spreading rumours’ Yet it soon became obvious that Covid-19 is far more dangerous than the flu, and Dr Li Wenliang, aged 33, died of the infection on 7 February 2020 (Hegarty 2020) In spite of their harsh initial reactions to Dr Li Wenliang’s alleged whistleblowing, Chinese authorities soon exhibited remarkable determination in containing the virus By late January, they quarantined the city of Wuhan (11 million inhabitants) and several other areas affecting over 60 million of people ‘Since February 18, China has reported the number of recovered cases is vastly outpacing the number of new confirmed cases each day ’ (Roper 2020) In the meantime, the coronavirus has crossed the borders of China, and Western countries have been much slower in their response On 11 March, the World Health Organization ‘declared COVID-19 a pandemic, pointing to the over 118,000 cases of the coronavirus illness in over 110 countries and territories around the world and the sustained risk of further global spread’ (Ducharme 2020) and on 13 March, ‘[i] nternational health officials said Friday that Europe has become the epicenter of the coronavirus pandemic, as the continent is now producing more new cases each day than China did at the height of its crisis’ (Coote and Jacobson 2020) In popular media, the Covid-19 pandemic has started an infodemic of unprecedented scale;fake news and bullshit flourish alongside credible information from sources such as the World Health Organization In the context of research, the Covid-19 pandemic has initiated historically unprecedented levels of collaboration and openness, prompting some authors to suggest that ‘[w] hen the story of the coronavirus (2019-nCOV) is finally written, it might well become a template for the utopian dream of open science — where research data is shared freely, unrestrained by competition, paywalls and patents’ (Crowe 2020) Worldwide closures of schools and universities have pushed millions of students and teachers online, bringing decades of experience in the field under the public eye (Bates 2020) Commentators compare Chinese and Western responses to the crisis, often under bombastic titles such as ‘Coronavirus and the Clash of Civilizations’ (Maçães 2020) Political scientists discuss whether the pandemic is an argument for total dismissal of capitalism or just a passing aberration in its functioning (Roberts 2020) Economists advise us to prepare the new recession (Elliott 2020) Sociologists see worldwide border closures as an anti-globalization experiment (Peters et al 2020), and philosophers go back to questions pertaining to human nature Worldwide governments are responding in radically different ways—the government of Montenegro has closed down the whole country before it registered the first patient within its borders (World Health Organization 2020b), while the UK has opted for a laissez faire approach which is hoped to result in herd immunity (Dunn and Kahn 2020) From official news to social networks, everyone and anyone has something to contribute to these debates, creating an infodemic which will be analysed long after Covid-19 is gone As I write these words on 16 March 2020 from self-isolation in my flat in Zagreb, Croatia, the future of the pandemic is unclear We have no idea what percentage of the global population will be affected by the virus, whether the virus will mutate, how many people the virus might kill, and what might happen with our politics and economy after the pandemic is gone At this point, we need to develop immediate measures to protect ourselves individually and collectively—weed out reliable information, self-isolate, reduce panic, develop educated guesses and emergency plans However, these urgent measures cannot arrive from thin air, and it is just as important to step back and take a birds-eye, longue durée view at the pandemic While doctors, nurses, politicians, food suppliers, and many other brave people self-sacrifice to support our daily survival, this editorial argues that academics have a unique opportunity, and a moral duty, to immediately start conducting in-depth studies of current events [truncated]

negative: Enhanced identification of viral and atypical bacterial pathogens in lower respiratory tract samples with nucleic acid amplification tests The advantages of nucleic acid amplification tests (NAT) over conventional methods for the detection of pathogens in lower respiratory tract samples have not been established. NAT for respiratory pathogens were performed on 439 endotracheal tube (ETT) and bronchoalveolar lavage (BAL) samples. A potential pathogen was detected in 87 samples. Of 22 samples that tested positive by conventional methods, 15 tested positive for the same pathogen by NAT, 1 tested positive for a different pathogen, 2 had co‐infections identified only by NAT, and 4 tested negative by NAT. An additional 73 pathogens were detected by NAT in 65 samples including 30 pathogens that were missed by conventional methods (19 adenovirus, 6 respiratory syncytial virus, 3 parainfluenza virus 1–4, 2 influenza A), 41 pathogens not routinely identified by conventional methods in most laboratories (23 rhinovirus, 8 human coronavirus OC43, 5 human metapneumovirus (hMPV), 2 human coronavirus 229E, 2 human coronavirus NL63, 1 Chlamydophila pneumoniae) and 2 pathogens from samples where no respiratory virus testing was requested (1 influenza A, 1 parainfluenza virus). Four of 52 patients who had multiple BAL samples submitted on the same day had negative and positive results by NAT on different samples. NAT improves detection of potential pathogens from ETT and BAL samples. J. Med. Virol. 78:702–710, 2006. © 2006 Wiley‐Liss, Inc.

negative: Respiratory viral infections during the 2009–2010 winter season in Central England, UK: incidence and patterns of multiple virus co-infections Acute viral respiratory infections are the most common infections in humans. Co-infection with different respiratory viruses is well documented but not necessarily well understood. The aim of this study was to utilise laboratory data from the winter season following the 2009 influenza A(H1N1) outbreak to investigate rates of respiratory virus co-infections, virus prevalence in different age groups and temporal variations in virus detection. The Health Protection Agency Public Health Laboratory (HPA PHL) Birmingham, UK, routinely uses polymerase chain reaction (PCR) to detect common respiratory viruses. The results from specimens received for respiratory virus investigations from late September 2009 to April 2010 were analysed. A total of 4,821 specimen results were analysed. Of these, 323 (13.2 %) had co-detections of two viruses, 22 (0.9 %) had three viruses and four (0.2 %) had four viruses. Reciprocal patterns of positive or negative associations between different virus pairs were found. Statistical analysis confirmed the significance of negative associations between influenza A and human metapneumovirus (HMPV), and influenza A and rhinovirus. Positive associations between parainfluenza with rhinovirus, rhinovirus with respiratory syncytial virus (RSV) and adenovirus with rhinovirus, parainfluenza and RSV were also significant. Age and temporal distributions of the different viruses were typical. This study found that the co-detection of different respiratory viruses is not random and most associations are reciprocal, either positively or negatively. The pandemic strain of influenza A(H1N1) was notable in that it was the least likely to be co-detected with another respiratory virus.

negative: Influenza Sentinel Surveillance and Severe Acute Respiratory Infection in a Reference Hospital in Southern Brazil INTRODUCTION: We report the results of the active surveillance of influenza infections in hospitalized patients and the evaluation of the seasonality and correlation with temperature and rainfall data. METHODS: During the 2-year study period, 775 patients were tested for 15 respiratory viruses (RVs). RESULTS: Most of the 57% of (n=444) virus-positive samples were human rhinovirus and respiratory syncytial virus. However, 10.4% (n=46) were influenza virus (80% FluA; 20% FluB). Age and SARI were significantly associated with influenza. FluB circulation was higher is 2013. CONCLUSIONS: In the post-epidemic period, influenza remains an important cause of hospitalization in SARI patients.

negative: Clinical features of deaths in the novel coronavirus epidemic in China In response to the recent novel coronavirus outbreak originating in Wuhan, Hubei province, China, observations concerning novel coronavirus mortality are of urgent public health importance. The present work presents the first review of the fatal novel coronavirus cases in China. Clinical data of fatal cases published by the Chinese Government were studied. As of 2 February 2020, the clinical data of 46 fatal cases were identified. The case fatality rate was significantly higher in Hubei province than the rest of China. While 67% of all deceased patients were male, gender was unlikely to be associated with mortality. Diabetes was likely to be associated with mortality. There is, however, not yet sufficient evidence to support the association between hypertension and mortality as similar prevalence of hypertension was also observed in the Hubei population.

negative: Why such excess of mortality for COVID-19 in Spain?

negative: Inter‐country Distancing, Globalization and the Coronavirus Pandemic Originating in China, the Coronavirus has reached the world at different speeds and levels of strength. This paper provides an initial understanding of some driving factors and their consequences. Since transmission requires people, the human factor behind globalization is essential. Globalization, a major force behind global wellbeing and equality, is highly associated with this factor. The analysis investigates the impact globalization has on the speed of initial transmission to a country and on the scale of initial infections in the context of other driving factors. Our cross‐country analysis finds that measures of globalization are positively related to the spread of the virus, both in speed and scale. However, the study also finds that globalized countries are better equipped to keep fatality rates low. The conclusion is not to reduce globalization to avoid pandemics, but to better monitor the human factor at the outbreak and mobilize collaboration forces to curtail diseases.

negative: Oncology Nursing During a Pandemic: Critical Reflections in the Context of COVID-19 Abstract Objectives To provide a critical reflection of COVID-19 in the context of oncology nursing and provide recommendations for caring for people affected by cancer during this pandemic. Data sources Electronic databases including CINAHL, MEDLINE, PsychINFO, Scopus, professional websites, and grey literature were searched using Google scholar. Conclusion Nurses are key stakeholders in developing and implementing policies regarding standards of care during COVID-19 pandemic. This pandemic poses several challenges for oncology services. Oncology nurses are providing a pivotal role in the care and management of the novel COVID-19 in the year landmarked as the International Year of the Nurse. Implications for practice It is too early to tell what shape this pandemic will take and its impact on oncology care. However, several important clinical considerations have been discussed to inform oncology nursing care and practice.

negative: Chapter 21 New Emerging Viruses Abstract Newly emerging viruses such as the Ebola virus, severe acute respiratory syndrome (SARS)-, Middle East respiratory syndrome (MERS)-coronavirus, and the avian influenza virus are serious threats to public health and have become a global concern. The swine flu pandemic which occurred in 2009 reminded us of the Spanish flu that killed over 40 million people. Newly emerging viruses could be either a novel previously undescribed virus or a variant of a previously known virus. Examples of the novel viruses include HIV, the Ebola virus, and SARS viruses. Variants of previously described viruses are also called “remerging viruses.” They are mutants of known viruses but cause new epidemics with considerable virulence. The influenza virus that caused the 2009 swine flu pandemic was a variant of an existing virus.

negative: The impact of influenza infection on young children, their family and the health care system BACKGROUND: Influenza is a major cause of respiratory illness in young children. Assessing the impact of infection on children and the community is required to guide immunisation policies. OBJECTIVES: To describe the impact of laboratory‐proven influenza in young children and to compare its impact with that of other respiratory viruses on the child, their family and the health care system. METHODS: Preschool children presenting for care or admission to a tertiary paediatric hospital during the 2008‐2014 influenza seasons were tested for respiratory virus by polymerase chain reaction and culture. Parental surveys were used to determine the impact of infection on illness duration, medication use, absenteeism and health service utilisation. Multivariate regression analyses were used to assess the impact of influenza and to evaluate the association between influenza status and outcomes. RESULTS: Among 1191 children assessed, 238 had influenza. Among children with influenza, 87.8% were administered antipyretics and 40.9% antibiotics. 28.6% had secondary complications. 65.4% of children missed school/day care, and 53.4% of parents missed work. When influenza and other viruses were compared, significant differences were noted including duration of illness (influenza: 9.54 days, other viruses: 8.50 days; P = 0.005) and duration of absenteeism for both the child (23.1 vs 17.3 hours; P = 0.015) and their parents (28.5 vs 22.7 hours; P = 0.012). CONCLUSIONS: Influenza infection in young children has a significant impact on medication use, absenteeism and the use of health care service. Significant differences are identified when compared with other ILI. These data demonstrate that influenza prevention strategies including immunisation are likely to have wide and significant impacts.

negative: Paramyxoviruses respiratory syncytial virus, parainfluenza virus, and human metapneumovirus infection in pediatric hospitalized patients and climate correlation in a subtropical region of southern China: a 7-year survey To investigate the features of paramyxovirus respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (HMPV) infection and determine the effect of meteorological conditions in Guangzhou, a subtropical region of southern China. We collected 11,398 respiratory samples from hospitalized pediatric patients with acute respiratory illness between July 2009 and June 2016 in Guangzhou. The samples were tested simultaneously for 18 respiratory pathogens using real-time PCR. Local meteorological data were also collected for correlation analysis. Of 11,398 patients tested, 5606 (49.2%) patients tested positive for one or more pathogens; RSV, PIV, and HMPV were the first, sixth, and ninth most frequently detected pathogens, in 1690 (14.8%), 502 (4.4%), and 321 (2.8%) patients, respectively. A total 17.9% (4605/5606) of patients with positive results had coinfection with other pathogens. Significant differences were found in the prevalence of RSV, PIV, and HMPV among all age groups (p < 0.001). RSV and HMPV had similar seasonal patterns, with two prevalence peaks every year. PIV appeared alternatively with RSV and HMPV. Multiple linear regression models were established for RSV, PIV, and HMPV prevalence and meteorological factors (p < 0.05). RSV and PIV incidence was negatively correlated with monthly mean relative humidity; RSV and HMPV incidence was negatively correlated with sunshine duration; PIV incidence was positively correlated with mean temperature. We described the features of paramyxovirus infection in a subtropical region of China and highlighted the correlation with meteorological factors. These findings will assist public health authorities and clinicians in improving strategies for controlling paramyxovirus infection.

negative: The relationship between obsessive compulsive beliefs and symptoms, anxiety and disgust sensitivity, and Swine Flu fears Abstract Using the 2009 Swine Flu outbreak as a contemporary example of pandemic fears, this study examined the relationship between various symptoms related to anxiety sensitivity and Swine Flu fears. It was hypothesized that both obsessive–compulsive (OC) beliefs and OC symptoms would significantly predict Swine Flu fears. It was also hypothesized that symptoms of anxiety, including measures of anxiety sensitivity and disgust sensitivity would significantly mediate the relationship between both OC beliefs and OC symptoms and Swine Flu fears. A total of 393 undergraduate students completed measures of Swine Flu fears, anxiety sensitivity, OC beliefs and symptoms, and disgust sensitivity. It was found that both OC beliefs and OC symptoms significantly predicted Swine Flu fears. While disgust sensitivity significantly mediated the relationship between both OC beliefs and OC symptoms and Swine Flu fears using the Sobel test, anxiety sensitivity was a significant mediator only for OC symptoms. Additionally, path modeling showed that anxiety sensitivity mediated the relationship between OC symptoms and Swine Flu fears best. The results of this study may be useful for treating individuals suffering from anxiety in light of future pandemics, as well as continuing to research the role of anxiety symptoms in predicting pandemic fears.

negative: A cross-sectional survey to evaluate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination among European travellers to resource-limited destinations BACKGROUND: Influenza is one of the most common vaccine-preventable diseases in travellers. By performing two cross-sectional questionnaire surveys during winter 2009 and winter 2010 among European travellers to resource-limited destinations, we aimed to investigate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination. METHODS: Questionnaires were distributed in the waiting room to the visitors of the University of Zurich Centre for Travel' Health (CTH) in January and February 2009 and January 2010 prior to travel health counselling (CTH09 and CTH10). Questions included demographic data, travel-related characteristics and KAP regarding influenza vaccination. Data were analysed by using SPSS(® )version 14.0 for Windows. Differences in proportions were compared using the Chi-square test and the significance level was set at p ≤ 0.05. Predictors for seasonal and pandemic influenza vaccination were determined by multiple logistic regression analyses. RESULTS: With a response rate of 96.6%, 906 individuals were enrolled and 868 (92.5%) provided complete data. Seasonal influenza vaccination coverage was 13.7% (n = 119). Only 43 (14.2%) participants were vaccinated against pandemic influenza A/H1N1, mostly having received both vaccines simultaneously, the seasonal and pandemic one. Job-related purposes (44, 37%), age > 64 yrs (25, 21%) and recommendations of the family physician (27, 22.7%) were the most often reported reasons for being vaccinated. In the multiple logistic regression analyses of the pooled data increasing age (OR = 1.03, 95% CI 1.01 - 1.04), a business trip (OR = 0.39, 95% CI 0.17 - 0.92) and seasonal influenza vaccination in the previous winter seasons (OR = 12.91, 95% CI 8.09 - 20.58) were independent predictors for seasonal influenza vaccination in 2009 or 2010. Influenza vaccination recommended by the family doctor (327, 37.7%), travel to regions with known high risk of influenza (305, 35.1%), and influenza vaccination required for job purposes (233, 26.8%) were most frequently mentioned to consider influenza vaccination. CONCLUSIONS: Risk perception and vaccination coverage concerning seasonal and pandemic influenza was very poor among travellers to resource-limited destinations when compared to traditional at-risk groups. Previous access to influenza vaccination substantially facilitated vaccinations in the subsequent year. Information strategies about influenza should be intensified and include health professionals, e.g. family physicians, travel medicine practitioners and business enterprises.

negative: XIth International Symposium on Respiratory Viral Infections Please cite this paper as: Belser et al. (2011) XIth International Symposium on Respiratory Viral Infections. Influenza and Other Respiratory Viruses 5(6), 443–e457.

negative: Phylodynamic Inference and Model Assessment with Approximate Bayesian Computation: Influenza as a Case Study A key priority in infectious disease research is to understand the ecological and evolutionary drivers of viral diseases from data on disease incidence as well as viral genetic and antigenic variation. We propose using a simulation-based, Bayesian method known as Approximate Bayesian Computation (ABC) to fit and assess phylodynamic models that simulate pathogen evolution and ecology against summaries of these data. We illustrate the versatility of the method by analyzing two spatial models describing the phylodynamics of interpandemic human influenza virus subtype A(H3N2). The first model captures antigenic drift phenomenologically with continuously waning immunity, and the second epochal evolution model describes the replacement of major, relatively long-lived antigenic clusters. Combining features of long-term surveillance data from the Netherlands with features of influenza A (H3N2) hemagglutinin gene sequences sampled in northern Europe, key phylodynamic parameters can be estimated with ABC. Goodness-of-fit analyses reveal that the irregularity in interannual incidence and H3N2's ladder-like hemagglutinin phylogeny are quantitatively only reproduced under the epochal evolution model within a spatial context. However, the concomitant incidence dynamics result in a very large reproductive number and are not consistent with empirical estimates of H3N2's population level attack rate. These results demonstrate that the interactions between the evolutionary and ecological processes impose multiple quantitative constraints on the phylodynamic trajectories of influenza A(H3N2), so that sequence and surveillance data can be used synergistically. ABC, one of several data synthesis approaches, can easily interface a broad class of phylodynamic models with various types of data but requires careful calibration of the summaries and tolerance parameters.

negative: Regional Diversification of Influenza Activity in Poland During the 2015/16 Epidemic Season The National Influenza Center (NIC) at the Department of Influenza Research of the National Institute for Public Health–National Institute of Hygiene (NIPH-NIH) participates in the Global Influenza Surveillance and Response System (GISRS) and continuously coordinates epidemiological and virological surveillance of influenza in Poland. The aim of this study was to determine the regional differences of influenza activity in Poland in the 2015/16 epidemic season. The influenza surveillance involved 16 administrative districts in which there are Voivodeship (province) Sanitary Epidemiological Stations set up to report influenza and influenza-like illness among the Polish population. Over 8000 specimens were tested in the season with regard to the respiratory viral infections in all regions investigated. The circulation of influenza viruses A and B was confirmed, with the subtype A/H1N1/pdm09 being predominant in the Pomerania, Podlaskie, Subcarpathian, Lubuskie, Silesian, and Warmian-Masuria provinces. The influenza-like virus occurred in individual cases, except for respiratory syncytial virus that also was detected in the Greater Poland and Warmia-Masuria provinces. The highest incidence of cases and suspected cases of influenza was recorded in Pomerania and the lowest one in Lubuskie provinces. The knowledge of regional differences in influenza activity is important for streamlining the distribution of preventive, therapeutic, and economic resources to combat the epidemic.

negative: Global epidemiology of non-influenza RNA respiratory viruses: data gaps and a growing need for surveillance Summary Together with influenza, the non-influenza RNA respiratory viruses (NIRVs), which include respiratory syncytial virus, parainfluenza viruses, coronavirus, rhinovirus, and human metapneumovirus, represent a considerable global health burden, as recognised by WHO's Battle against Respiratory Viruses initiative. By contrast with influenza viruses, little is known about the contemporaneous global diversity of these viruses, and the relevance of such for development of pharmaceutical interventions. Although far less advanced than for influenza, antiviral drugs and vaccines are in different stages of development for several of these viruses, but no interventions have been licensed. This scarcity of global genetic data represents a substantial knowledge gap and impediment to the eventual licensing of new antiviral drugs and vaccines for NIRVs. Enhanced genetic surveillance will assist and boost research and development into new antiviral drugs and vaccines for these viruses. Additionally, understanding the global diversity of respiratory viruses is also part of emerging disease preparedness, because non-human coronaviruses and paramyxoviruses have been listed as priority concerns in a recent WHO research and development blueprint initiative for emerging infectious diseases. In this Personal View, we explain further the rationale for expanding the genetic database of NIRVs and emphasise the need for greater investment in this area of research.

negative: Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease BACKGROUND: Acute viral respiratory infections are an important cause of morbidity and mortality in humans worldwide. The etiological backgrounds of these infections remain unconfirmed in most clinical cases. The aim of this study was to estimate the prevalence of human coronavirus infections in a series of children hospitalized with symptoms of acute respiratory tract disease in a one-year period in Slovenia. METHODS: The 664 specimens from 592 children under six years of age hospitalized at the University Children’s Hospital in Ljubljana were sent for the routine laboratory detection of respiratory viruses. Respiratory viruses were detected with a direct immunofluorescence assay and human coronaviruses were detected with a modified real-time RT–PCR. RESULTS: HCoV RNA was detected in 40 (6%, 95% CI: 4.3%–8.1%) of 664 samples. Of these specimens, 21/40 (52.5%) were identified as species HKU1, 7/40 (17.5%) as OC43, 6/40 (15%) as 229E, and 6/40 (15%) as NL63. Infection with HCoV occurred as a coinfection with one or more other viruses in most samples (70%). Of the HCoV-positive children, 70.3% had lower respiratory tract infections. CONCLUSION: The results of our study show that HCoV are frequently detected human pathogens, often associated with other respiratory viruses and acute respiratory tract infections in hospitalized children. An association between age and the viral load was found. The highest viral load was detected in children approximately 10 months of age.

negative: Cerebrovascular Accident in a Pediatric Patient Presenting With Influenza Abstract Background Acute ischemic stroke (AIS) in pediatric populations accounts for more than half of pediatric strokes and is associated with significant morbidity and mortality. Pediatric AIS can present with nonspecific symptoms or symptoms that mimic alternate pathology. Case Report A 4-month-old female presented to the emergency department for fever, decreased oral intake, and “limp” appearance after antibiotic administration. She was febrile, tachypneic, and hypoxic. Her skin was mottled with 3-s capillary refill, her anterior fontanelle was tense, and she had mute Babinski reflex bilaterally but was moving all extremities. The patient was hyponatremic, thrombocytopenic, and tested positive for influenza A. A computed tomography scan of the brain revealed an acute infarction involving the right frontal, parietal, temporal, and occipital lobes in addition to hyperdensities concerning for thrombosed cortical veins. The patient was transferred for specialty evaluation and was discharged 2 weeks later on levetiracetam. Why Should an Emergency Physician be Aware of This? Pediatric AIS can present with nonspecific symptoms that mimic alternate pathology. A high level of suspicion is needed so as not to miss the diagnosis of pediatric AIS in the emergency department. A thorough neurologic assessment is warranted, and subtle abnormalities should be investigated further.

negative: New evidence in infective and cardiovascular medicine

negative: Why do I need it? I am not at risk! Public perceptions towards the pandemic (H1N1) 2009 vaccine BACKGROUND: On the 30th September 2009, the pandemic (H1N1) 2009 influenza vaccine was made available to adults and children aged 10 years and over, in Australia. Acceptance of a novel vaccine is influenced by perceptions of risk including risk of infection, risk of death or severe illness and risk of serious vaccine side-effects. We surveyed a sample of residents from Sydney, Australia to ascertain their risk perception, attitudes towards the pandemic and willingness to accept the pandemic (H1N1) 2009 influenza vaccine. METHODS: We sampled residents using a cross-sectional intercept design during the WHO Phase 6. Members of the public were approached in shopping and pedestrian malls to undertake the survey during September and October 2009. The survey measured perceived risk, seriousness of disease, recent behavioural changes, likely acceptance of the pandemic (H1N1) 2009 vaccine and issues relating to uptake and perceived safety. RESULTS: Of the 627 respondents, the majority felt that they had a "very low to low" (332/627, 52.9%) risk of acquiring H1N1. 24.5% (154/627) of respondents believed that the disease would "very seriously or extremely" affect their health. Nearly half (305/627, 48.6%) reported that in response to the "swine flu" outbreak they had undertaken one or more of the investigated behavioural changes. Overall, the self-reported likelihood of accepting vaccination against novel H1N1 was 54.7% (343/627). CONCLUSIONS: While, most participants did not believe they were at high risk of acquiring pandemic H1N1 2009, over half of the sample indicated that they would accept the vaccine. Participants who were vaccinated against the seasonal influenza were more likely to receive the H1N1 vaccine. Concerns about safety, the possibility of side effects and the vaccine development process need to be addressed.

negative: Genomics of COVID-19: molecular mechanisms going from susceptibility to severity of the disease

negative: A weapon the world needs Both bottom-up and top-down planning is needed to prevent a global economic disaster. Michael T. Osterholm calls for action at all levels.

negative: Abnormal Hemostatic Parameters and Risk of Thromboembolism Among Patients With COVID-19 Infection

negative: Identification and evolutionary dynamics of two novel human coronavirus OC43 genotypes associated with acute respiratory infections: phylogenetic, spatiotemporal and transmission network analyses Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.

negative: Human brain evolution and the “Neuroevolutionary Time-depth Principle:” Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this goal mostly achieved, discussion of etiological factors should be reintroduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the “development of a pathophysiologically based classification system”. The author critically reviews the neuroevolutionary literature on stress-induced and fear circuitry disorders and related amygdala-driven, species-atypical fear behaviors of clinical severity in adult humans. Over 30 empirically testable/falsifiable predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is neither mode-of-acquisition-based nor brain-evolution-based. For example, snake phobia (innate) and dog phobia (overconsolidational) are clustered together. Similarly, research on blood-injection-injury-type-specific phobia clusters two fears different in their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's blood or a sharp object penetrating one's skin. Genetic architecture-charting of fear-circuitry-related traits has been challenging. Various, non-phenotype-based architectures can serve as targets for research. In this article, the author will propose one such alternative genetic architecture. This article was inspired by the following: A) Nesse's “Smoke-Detector Principle”, B) the increasing suspicion that the “smooth” rather than “lumpy” distribution of complex psychiatric phenotypes (including fear-circuitry disorders) may in some cases be accounted for by oligogenic (and not necessarily polygenic) transmission, and C) insights from the initial sequence of the chimpanzee genome and comparison with the human genome by the Chimpanzee Sequencing and Analysis Consortium published in late 2005. Neuroevolutionary insights relevant to fear circuitry symptoms that primarily emerge overconsolidationally (especially Combat related Posttraumatic Stress Disorder) are presented. Also introduced is a human-evolution-based principle for clustering innate fear traits. The “Neuroevolutionary Time-depth Principle” of innate fears proposed in this article may be useful in the development of a neuroevolution-based taxonomic re-clustering of stress-triggered and fear-circuitry disorders in DSM-V. Four broad clusters of evolved fear circuits are proposed based on their time-depths: 1) Mesozoic (mammalian-wide) circuits hardwired by wild-type alleles driven to fixation by Mesozoic selective sweeps; 2) Cenozoic (simian-wide) circuits relevant to many specific phobias; 3) mid Paleolithic and upper Paleolithic (Homo sapiens-specific) circuits (arguably resulting mostly from mate-choice-driven stabilizing selection); 4) Neolithic circuits (arguably mostly related to stabilizing selection driven by gene–culture co-evolution). More importantly, the author presents evolutionary perspectives on warzone-related PTSD, Combat-Stress Reaction, Combat-related Stress, Operational-Stress, and other deployment-stress-induced symptoms. The Neuroevolutionary Time-depth Principle presented in this article may help explain the dissimilar stress-resilience levels following different types of acute threat to survival of oneself or one's progency (aka DSM-III and DSM-V PTSD Criterion-A events). PTSD rates following exposure to lethal inter-group violence (combat, warzone exposure or intentionally caused disasters such as terrorism) are usually 5–10 times higher than rates following large-scale natural disasters such as forest fires, floods, hurricanes, volcanic eruptions, and earthquakes. The author predicts that both intentionally-caused large-scale bioevent-disasters, as well as natural bioevents such as SARS and avian flu pandemics will be an exception and are likely to be followed by PTSD rates approaching those that follow warzone exposure. During bioevents, Amygdala-driven and locus-coeruleus-driven epidemic pseudosomatic symptoms may be an order of magnitude more common than infection-caused cytokine-driven symptoms. Implications for the red cross and FEMA are discussed. It is also argued that hospital phobia as well as dog phobia, bird phobia and bat phobia require re-taxonomization in DSM-V in a new “overconsolidational disorders” category anchored around PTSD. The overconsolidational spectrum category may be conceptualized as straddling the fear circuitry spectrum disorders and the affective spectrum disorders categories, and may be a category for which Pitman's secondary prevention propranolol regimen may be specifically indicated as a “morning after pill” intervention. Predictions are presented regarding obsessive-compulsive disorder (OCD) (e.g., female-pattern hoarding vs. male-pattern hoarding) and “culture-bound” acute anxiety symptoms (taijin-kyofusho, koro, shuk yang, shook yong, suo yang, rok-joo, jinjinia-bemar, karoshi, gwarosa, Voodoo death). Also discussed are insights relevant to pseudoneurological symptoms and to the forthcoming Dissociative-Conversive disorders category in DSM-V, including what the author terms fright-triggered acute pseudo-localized symptoms (i.e., pseudoparalysis, pseudocerebellar imbalance, psychogenic blindness, pseudoseizures, and epidemic sociogenic illness). Speculations based on studies of the human abnormal-spindle-like, microcephaly-associated (ASPM) gene, the microcephaly primary autosomal recessive (MCPH) gene, and the forkhead box p2 (FOXP2) gene are made and incorporated into what is termed “The pre-FOXP2 Hypothesis of Blood-Injection-Injury Phobia.” Finally, the author argues for a non-reductionistic fusion of “distal (evolutionary) neurobiology” with clinical “proximal neurobiology,” utilizing neurological heuristics. It is noted that the value of re-clustering fear traits based on behavioral ethology, human-phylogenomics-derived endophenotypes and on ontogenomics (gene–environment interactions) can be confirmed or disconfirmed using epidemiological or twin studies and psychiatric genomics.

negative: Awareness, Attitudes, and Actions Related to COVID-19 Among Adults With Chronic Conditions at the Onset of the U.S. Outbreak: A Cross-sectional Survey Background: The evolving outbreak of coronavirus disease 2019 (COVID-19) is requiring social distancing and other measures to protect public health. However, messaging has been inconsistent and unclear. Objective: To determine COVID-19 awareness, knowledge, attitudes, and related behaviors among U.S. adults who are more vulnerable to complications of infection because of age and comorbid conditions. Design: Cross-sectional survey linked to 3 active clinical trials and 1 cohort study. Setting: 5 academic internal medicine practices and 2 federally qualified health centers. Patients: 630 adults aged 23 to 88 years living with 1 or more chronic conditions. Measurements: Self-reported knowledge, attitudes, and behaviors related to COVID-19. Results: A fourth (24.6%) of participants were "very worried" about getting the coronavirus. Nearly a third could not correctly identify symptoms (28.3%) or ways to prevent infection (30.2%). One in 4 adults (24.6%) believed that they were "not at all likely" to get the virus, and 21.9% reported that COVID-19 had little or no effect on their daily routine. One in 10 respondents was very confident that the federal government could prevent a nationwide outbreak. In multivariable analyses, participants who were black, were living below the poverty level, and had low health literacy were more likely to be less worried about COVID-19, to not believe that they would become infected, and to feel less prepared for an outbreak. Those with low health literacy had greater confidence in the federal government response. Limitation: Cross-sectional study of adults with underlying health conditions in 1 city during the initial week of the COVID-19 U.S. outbreak. Conclusion: Many adults with comorbid conditions lacked critical knowledge about COVID-19 and, despite concern, were not changing routines or plans. Noted disparities suggest that greater public health efforts may be needed to mobilize the most vulnerable communities. Primary Funding Source: National Institutes of Health.

negative: Predict the next moves of COVID-19: reveal the temperate and tropical countries scenario The spread of COVID-19 engulfs almost all the countries and territories of the planet, and infections and fatality are increasing rapidly. The first epi-center of its' massive spread was in Wuhan, Hubei province, China having a temperate weather, but the spread has got an unprecedented momentum in European temperate countries mainly in Italy and Spain (as of March 30, 2020). However, Malaysia and Singapore and the neighboring tropical countries of China got relatively low spread and fatality that created a research interest on whether there are potential impacts of weather condition on COVID-19 spread. Adopting the SIR (Susceptible Infected Removed) deviated model to predict potential cases and death in the coming days from COVID-19 was done using the secondary and official sources of data. This study shows that COVID-19 spread and fatality tend to be high across the world but compared to tropical countries, it is going to be incredibly high in the temperate countries having lower temperature (7-16°C) and humidity (80-90%) in last March. However, some literature predicted that this might not to be true, rather irrespective of weather conditions there might be a continuous spread and death. Moreover, a large number of asymptotic COVID-19 carrier in both temperate and tropical countries may re-outbreak in the coming winter. Therefore, a comprehensive global program with the leadership of WHO for testing of entire population of the world is required, which will be very useful for the individual states to take proper political action, social movement and medical services.

negative: Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. The outbreak of COVID-19 poses unprecedent challenges to global health1. The new coronavirus, SARS-CoV-2, shares high sequence identity to SARS-CoV and a bat coronavirus RaTG132. While bats may be the reservoir host for various coronaviruses3,4, whether SARS-CoV-2 has other hosts remains ambiguous. In this study, one coronavirus isolated from a Malayan pangolin showed 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S genes, respectively. In particular, the receptor-binding domain within the S protein of the Pangolin-CoV is virtually identical to that of SARS-CoV-2, with one noncritical amino acid difference. Results of comparative genomic analysis suggest that SARS-CoV-2 might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. The Pangolin-CoV was detected in 17 of 25 Malayan pangolins analyzed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against Pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus that is highly related to SARS-CoV-2 in pangolins suggests that they have the potential to act as the intermediate host of SARS-CoV-2. The newly identified coronavirus in the most-trafficked mammal could represent a future threat to public health if wildlife trade is not effectively controlled.

negative: Incubation period as part of the case definition of severe respiratory illness caused by a novel coronavirus. Non-specific symptoms of acute respiratory viral infections make it difficult for many countries without ongoing transmission of a novel coronavirus to rule out other possibilities including influenza before isolating imported febrile individuals with a possible exposure history. The incubation period helps differential diagnosis, and up to two days is suggestive of influenza. It is worth including the incubation period in the case definition of novel coronavirus infection.

negative: The first 100 days: modeling the evolution of the COVID-19 pandemic A simple analytical model for modeling the evolution of the 2020 COVID-19 pandemic is presented. The model is based on the numerical solution of the widely used Susceptible-Infectious-Removed (SIR) populations model for describing epidemics. We consider an expanded version of the original Kermack-McKendrick model, which includes a decaying value of the parameter $\beta$ (the effective contact rate) due to externally imposed conditions, to which we refer as the forced-SIR (FSIR) model. We introduce an approximate analytical solution to the differential equations that represent the FSIR model which gives very reasonable fits to real data for a number of countries over a period of 100 days (from the first onset of exponential increase, in China). The proposed model contains 3 adjustable parameters which are obtained by fitting actual data (up to April 28, 2020). We analyze these results to infer the physical meaning of the parameters involved. We use the model to make predictions about the total expected number of infections in each country as well as the date when the number of infections will have reached 99% of this total. We also compare key findings of the model with recently reported results on the high contagiousness and rapid spread of the disease.

negative: Seroepidemiological analysis of influenza pandemics in Shizuoka Prefecture and all Japan Abstract (1) Seroepidemiological analysis of influenza pandemics (1986–2003) in Shizuoka Prefecture and all Japan revealed differences in geographical, annual, seasonal, and age distributions. (2) For 17 years, the pandemics generally began at the 50th week every year showing over 1.0 patient/clinic, reached the peak at 5th week the following year, and ended over 10–15th week. Two big A/H3N2 pandemics were seen in 1989/1990 and 1997/1998 seasons, claiming over 1 million patients in Japan. (3) As herald strains, A/H3N2 strains (A/Sydney-like) were found in October 1999, and B strains (B/Victoria- and B/Yamagata-like) were detected in July and November 1998 and, in August and December 2000 in Shizuoka. B/Shizuoka/1/98 strain was registered internationally as a vaccine-recommended strain. (4) A/H3N2 and B viruses were detected in 55–78% of flu patients (almost under 10 years) with encephalopathy in 1999/2000 and 78–91% in 2000/2001 by MDCK and reverse transcription polymerase chain reaction (RT-PCR) methods. (5) High hemagglutination inhibition (HI) titers over 40 in 250 persons were shown against A/Sydney/5/97 (H3N2), A/Yokohama/8/98 (H3N2), A/Panama/2007/99 (H3N2) and A/Moscow/10/99 (H1N1) strains, while low titers showed against A/Beijing/262/95 (H1N1) and A/New Caledonia/20/99 (H1N1), and B/Beijing/243/97, B/Shangdong/7/97 and B/Yamanashi/106/98 strains in 1998–2000. (6) In anti-HA titers against A/H3N2, A/H1N1 and B subtypes, clear generation gaps were observed between children (0–19 years), adults (20–59 years) and old men (over 60 years). (7) The pandemics are dependent on host immunity (acquired and vaccinated) and climatic conditions (low temperature, low humidity and limited rainfall), considering highly pathogenic avian influenza (HPAI) viruses (A/H5N1, A/H7N7) like severe acute respiratory syndrome (SARS) corona virus in 2002–2003.

negative: Gene Variations in Cis-Acting Elements between the Taiwan and Prototype Strains of Porcine Epidemic Diarrhea Virus Alter Viral Gene Expression In 2013, the outbreak of porcine epidemic diarrhea (PED) in Taiwan caused serious economic losses. In this study, we examined whether the variations of the cis-acting elements between the porcine epidemic diarrhea virus (PEDV) Taiwan (TW) strain and the prototype strain CV777 alter gene expression. For this aim, we analyzed the variations of the cis-acting elements in the 5′ and 3′ untranslated regions (UTRs) between the PEDV TW, CV777, and other reference strains. We also determined the previously unidentified transcription regulatory sequence (TRS), a sequence motif required for coronavirus transcription, and found that a nucleotide deletion in the TW strain, in comparison with CV777 strain, immediately downstream of the leader core sequence alters the identity between the leader TRS and the body TRS. Functional analyses using coronavirus defective interfering (DI) RNA revealed that such variations in cis-acting elements for the TW strain compared with the CV777 strain have an influence on the efficiency of gene expression. The current data show for the first time the evolution of PEDV in terms of cis-acting elements and their effects on gene expression, and thus may contribute to our understanding of recent PED outbreaks worldwide.

negative: Clinical and epidemiological characteristics of Coronavirus Disease 2019 (COVID-19) patients Background: Numerous groups have reported the clinical and epidemiological characteristics of Coronavirus Disease 2019 (COVID-19) cases; however, the data remained inconsistent. This paper aimed to pool the available data to provide a more complete picture of the characteristics of COVID-19 patients. Methods: A systematic review and pooled analysis was performed. Eligible studies were identified from database and hand searches up to March 2, 2020. Data on clinical (including laboratory and radiological) and epidemiological (including demographic) characteristics of confirmed COVID-19 cases were extracted and combined by simple pooling. Results: Of 644 studies identified, 69 studies (involving 48,926 patients) were included in the analysis. The average age of the patients was 49.16 years. A total of 51.46% of the patients were men and 52.32% were non-smokers. Hypertension (50.82%) and diabetes (20.89%) were the most frequent comorbidities observed. The most common symptoms were fever (83.21%), cough (61.74%), and myalgia or fatigue (30.22%). Altered levels of blood and biochemical parameters were observed in a proportion of the patients. Most of the patients (78.50%) had bilateral lung involvements, and 5.86% showed no CT findings indicative of viral pneumonia. Acute respiratory distress syndrome (28.36%), acute cardiac injury (7.89%) and acute kidney injury (7.60%) were the most common complications recorded. Conclusions: Clinical and epidemiological characteristics of COVID-19 patients were mostly heterogeneous and non-specific. This is the most comprehensive report of the characteristics of COVID-19 patients to date. The information presented is important for improving our understanding of the spectrum and impact of this novel disease.

negative: Advances in the Relationship Between Coronavirus Infection and Cardiovascular Diseases The outbreak of coronavirus disease 2019 (COVID-19) has once again aroused people's concern about coronavirus. Seven human coronaviruses (HCoVs) have been discovered so far, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU115, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. Existing studies show that the cardiovascular disease increased the incidence and severity of coronavirus infection. At the same time, myocardial injury caused by coronavirus infection is one of the main factors contributing to poor prognosis. In this review, the recent clinical findings about the relationship between coronaviruses and cardiovascular diseases and the underlying pathophysiological mechanisms are discussed. This review aimed to provide assistance for the prevention and treatment of COVID-19.

negative: Detection of respiratory viruses in sputum from adults by use of automated multiplex PCR. Respiratory tract infections (RTI) frequently cause hospital admissions among adults. Diagnostic viral reverse transcriptase PCR (RT-PCR) of nose and throat swabs (NTS) is useful for patient care by informing antiviral use and appropriate isolation. However, automated RT-PCR systems are not amenable to utilizing sputum due to its viscosity. We evaluated a simple method of processing sputum samples in a fully automated respiratory viral panel RT-PCR assay (FilmArray). Archived sputum and NTS samples collected in 2008-2012 from hospitalized adults with RTI were evaluated. A subset of sputum samples positive for 10 common viruses by a uniplex RT-PCR was selected. A sterile cotton-tip swab was dunked in sputum, swirled in 700 μL of sterile water (dunk and swirl method) and tested by the FilmArray assay. Quantitative RT-PCR was performed on "dunked" sputum and NTS samples for influenza A (Flu A), respiratory syncytial virus (RSV), coronavirus OC43 (OC43), and human metapneumovirus (HMPV). Viruses were identified in 31% of 965 illnesses using a uniplex RT-PCR. The sputum sample was the only sample positive for 105 subjects, including 35% (22/64) of influenza cases and significantly increased the diagnostic yield of NTS alone (302/965 [31%] versus 197/965 [20%]; P = 0.0001). Of 108 sputum samples evaluated by the FilmArray assay using the dunk and swirl method, 99 (92%) were positive. Quantitative RT-PCR revealed higher mean viral loads in dunked sputum samples compared to NTS samples for Flu A, RSV, and HMPV (P = 0.0001, P = 0.006, and P = 0.011, respectively). The dunk and swirl method is a simple and practical method for reliably processing sputum samples in a fully automated PCR system. The higher viral loads in sputa may increase detection over NTS testing alone.

negative: 6th International Conference on Emerging Zoonoses The 6th International Conference on Emerging Zoonoses, held at Cancun, Mexico, 24–27 February 2011, offered 84 participants from 18 countries, a snapshot of current research in numerous zoonoses caused by viruses, bacteria or prions. Co‐chaired by Professors Heinz Feldmann and Jürgen Richt, the conference explored 10 topics: (i) The ecology of emerging zoonotic diseases; (ii) The role of wildlife in emerging zoonoses; (iii) Cross‐species transmission of zoonotic pathogens; (iv) Emerging and neglected influenza viruses; (v) Haemorrhagic fever viruses; (vi) Emerging bacterial diseases; (vii) Outbreak responses to zoonotic diseases; (viii) Food‐borne zoonotic diseases; (ix) Prion diseases; and (x) Modelling and prediction of emergence of zoonoses. Human medicine, veterinary medicine and environmental challenges are viewed as a unity, which must be considered under the umbrella of ‘One Health’. Several presentations attempted to integrate the insights gained from field data with mathematical models in the search for effective control measures of specific zoonoses. The overriding objective of the research presentations was to create, improve and use the tools essential to address the risk of contagions in a globalized society. In seeking to fulfil this objective, a three‐step approach has often been applied: (i) use cultured cells, model and natural animal hosts and human clinical models to study infection; (ii) combine traditional histopathological and biochemical approaches with functional genomics, proteomics and computational biology; and (iii) obtain signatures of virulence and insights into mechanisms of host defense response, immune evasion and pathogenesis. This meeting review summarizes 39 of the conference presentations and mentions briefly the 16 articles in this Special Supplement, most of which were presented at the conference in earlier versions. The full affiliations of all presenters and many colleagues have been included to facilitate further inquiries from readers.

negative: Stalking new vaccines: Methods that target the stems of viral proteins could put universal vaccines within reach

negative: Uncertainty and Immunity in Public Communications on Pandemics This chapter examines uncertainty in the expert advice on pandemics given to members of the general public. The chapter draws on research conducted in Australia and Scotland on public engagements with the 2009 influenza (swine flu) pandemic and discusses implications for communications on more recent infectious disease outbreaks, including Ebola and Zika. It shows how public health messages aim to achieve a workable balance of warning and reassurance and deflect problems of trust in experts and science. The chapter considers how uncertainties which prevail in pandemics reinforce the personalization of responses to pandemic risk, in ways that undermine the cooperation and collective action which are also needed to respond effectively to pandemics.

negative: A data-driven model for influenza transmission incorporating media effects Numerous studies have attempted to model the effect of mass media on the transmission of diseases such as influenza; however, quantitative data on media engagement has until recently been difficult to obtain. With the recent explosion of ‘big data’ coming from online social media and the like, large volumes of data on a population’s engagement with mass media during an epidemic are becoming available to researchers. In this study, we combine an online dataset comprising millions of shared messages relating to influenza with traditional surveillance data on flu activity to suggest a functional form for the relationship between the two. Using this data, we present a simple deterministic model for influenza dynamics incorporating media effects, and show that such a model helps explain the dynamics of historical influenza outbreaks. Furthermore, through model selection we show that the proposed media function fits historical data better than other media functions proposed in earlier studies.

negative: Emerging Diseases at the Interface of People, Domestic Animals, and Wildlife

negative: Elucidating the differences in the molecular mechanism of receptor binding between 2019-nCoV and the SARS-CoV viruses using computational tools The outbreak of the 2019-nCoV coronavirus causing severe acute respiratory syndrome which can be fatal, especially in elderly population, has been declared a pandemic by the World Health Organization. Many biotechnology laboratories are rushing to develop therapeutic antibodies and antiviral drugs for treatment of this viral disease. The viral CoV spike (S) glycoprotein is one of the main targets for pharmacological intervention. Its receptor-binding domain (RBD) interacts with the human ACE2 receptor ensuring the entry of the viral genomes into the host cell. In this work, we report on the differences in the binding of the RBD of the previous coronavirus SARS-CoV and of the newer 2019-nCoV coronavirus to the human ACE2 receptor using atomistic molecular dynamics techniques. Our results show major mutations in the 2019-nCoV RBD with respect to the SARS-CoV RBD occurring at the interface of RBD-ACE2 complex. These mutations make the 2019-nCoV RBD protein backbone much more flexible, hydrophobic interactions are reduced and additional polar/charged residues appear at the interface. We observe that higher flexibility of the 2019-nCoV RBD with respect to the SARS-CoV RBD leads to a bigger binding interface between the 2019-nCoV RBD and ACE2 and to about 20% more contacts between them in comparison with SARS-CoV. Taken together, the 2019-nCoV RBD shows more stable binding interface and higher binding affinity for the ACE2 receptor. The mutations not only stabilize the binding interface, they also lead to overall more stable 2019-nCoV RBD protein structure, even far from the binding interface. Our results on the molecular differences in the binding between the two viruses can provide important inputs for development of appropriate antiviral treatments of the new viruses, addressing the necessity of ongoing pandemics.

negative: A commentary on “World Health Organization declares global emergency: A review of the 2019 novel Coronavirus (COVID-19)”

negative: A randomized controlled trial of low-dose recombinant human interferons α-2b nasal spray to prevent acute viral respiratory infections in military recruits Abstract The military population has a high disease burden of acute viral respiratory infections in China. To assess the efficacy and safety of a low-dose recombinant human interferon α-2b (rIFNα-2b) nasal spray in preventing acute viral respiratory infections in military population, we performed this randomized controlled trial. The results showed that application of the rIFNα-2b nasal spray had the benefits in prevention of infections caused by influenza A virus, influenza B virus parainfluenza viruses 1–3 and adenovirus species B. However, no benefit was seen in preventing respiratory syncytial virus. No severe adverse events were reported. Therefore, the rIFNα-2b nasal spray was effective and well tolerated for preventing common viral respiratory infections in the military recruits.

negative: Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis Background/Purpose Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. Methods We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. Results Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. Conclusion COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.

negative: Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction Historically, influenza pandemics have arisen from avian influenza viruses. Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates. Infection of humans with the highly pathogenic avian influenza H5N1 virus is associated with a mortality in excess of 60%, which has been attributed to dysregulation of the cytokine system. Human macrophages and epithelial cells infected with some genotypes of H5N1 and H9N2 viruses express markedly elevated cytokine and chemokine levels when compared with seasonal influenza A subtype H1N1 virus. The mechanisms underlying this cytokine and chemokine hyperinduction are not fully elucidated. In the present study, we demonstrate that autophagy, a tightly regulated homeostatic process for self-digestion of unwanted cellular subcomponents, plays a role in cytokine induction. Autophagy is induced to a greater extent by H9N2/G1, in association with cytokine hyperinduction, compared with H1N1 and the novel pandemic swine-origin influenza A/H1N1 viruses. Using 3-methyladenine to inhibit autophagy and small interfering RNA to silence the autophagy gene, Atg5, we further show that autophagic responses play a role in influenza virus-induced CXCL10 and interferon-α expression in primary human blood macrophages. Our results provide new insights into the pathogenic mechanisms of avian influenza viruses.

negative: 2019 Coronavirus pandemic in Turkey and across the world/ Dünyada ve Türkiye'de 2019 Koronavirüs Pandemisi The novel coronavirus, which was called 2019-nCoV at the beginning of the outbreak, was named SARS-CoV-2 later. The clinical disease caused by the virus was also called Coronavirus disease 2019 (COVID-19). World Health Organization declared COVID-19 a global pandemic on 11.03.2020. As of 26.03.2020, there have been 462.684 confirmed cases and 20.834 deaths globally, and these numbers are expected to increase in the coming days. The dynamics of virus spread are investigated with various models and outbreak parameters such as incubation time and basic reproduction number (R0) is tried to be illuminated. According to official numbers, as of 03.26.2020, there have also been 3629 cases and 75 deaths in Turkey. COVID-19 Guideline prepared by the Ministry of Health of the Republic of Turkey is constantly updated with additional prevention and treatment strategies. Various predictions are made for the future course of the pandemic, and the contribution of the spread of the virus in Africa and seasonal changes on this issue has been investigated.

negative: Losing ground at the wrong time: Trends in self-reported influenza vaccination uptake in Switzerland, Heath Survey 2007-2017 Objectives We studied time trends in seasonal influenza vaccination and associations with socioeconomic and health-related determinants in Switzerland, overall and in people aged [≥]65 years. Design Three cross-sectional surveys. Participants Individuals who participated in the Swiss Health Surveys 2007, 2012, and 2017. We calculated the proportion reporting influenza vaccination in the last 12 months, and performed multivariable logistic regression analyses. Results: The proportion of reporting a history of influenza vaccination overall was 31.9% (95% confidence intervals [95% CI] 31.4-32.4); and dropped from 34.5% in 2007 to 28.8% in 2017. The uptake of vaccination within the past 12 months was 16% in 2007 and similar in 2012 and 2017 (around 14%). In people with chronic disease, uptake dropped from 43.8% in 2007 to 37.1% in 2012 and to 31.6% in 2017 (p<0.001). In people aged [≥]65 years, uptake dropped from 47.8% in 2007 to 38.5% in 2012 to 36.2% in 2017 (p<0.001). Similarly, a decrease in vaccine uptake was seen in people with poor self-reported health status (39.4%, 33.1%, and 27.0%). In logistic regression, self-reported vaccination coverage decreased in the 65 to 75 years old (adjusted odds ratio (aOR) aOR 0.56, 95% Cl 0.48-0.66 between 2007 and 2012; aOR 0.89, 95% CI 0.77-1.03). Uptake was positively associated with the [≥]65 age group, living in French-speaking and urban areas, history of smoking, bad self-reported health status, private/semiprivate health insurance, having a medical profession, and having any underlying chronic disease. Use of any alternative medicine therapy was negatively associated with influenza vaccination (aOR 0.72, 95% CI 0.67-0.80). Conclusion: Influenza vaccination coverage was low in older and chronically ill persons. Significant efforts are required in preparing for the flu season 2020/21 to reduce the double burden of COVID-19 and seasonal influenza. These efforts should include campaigns but also novel approaches using social media.

negative: Influenza Influenza is a highly contagious, acute respiratory illness afflicting humans. Although influenza epidemics occur frequently, their severity varies (1). Not until 1933, when the first human influenza virus was isolated, was it possible to define with certainty which pandemics were caused by influenza viruses. In general, influenza A viruses are more pathogenic than are influenza B viruses. Influenza A virus is a zoonotic infection, and more than 100 types of influenza A viruses infect most species of birds, pigs, horses, dogs, and seals. It is believed that the 1918–1919 pandemic originated from a virulent strain of H1N1 from pigs and birds.

negative: The COVID-19 Infection in Italy: A Statistical Study of an Abnormally Severe Disease We statistically investigate the Coronavirus Disease 19 (COVID-19) pandemic, which became particularly invasive in Italy in March 2020. We show that the high apparent lethality or case fatality ratio (CFR) observed in Italy, as compared with other countries, is likely biased by a strong underestimation of the number of infection cases. To give a more realistic estimate of the lethality of COVID-19, we use the actual (March 2020) estimates of the infection fatality ratio (IFR) of the pandemic based on the minimum observed CFR and analyze data obtained from the Diamond Princess cruise ship, a good representation of a “laboratory” case-study from an isolated system in which all the people have been tested. From such analyses, we derive more realistic estimates of the real extent of the infection as well as more accurate indicators of how fast the infection propagates. We then isolate the dominant factors causing the abnormal severity of the disease in Italy. Finally, we use the death count—the only data estimated to be reliable enough—to predict the total number of people infected and the interval of time when the infection in Italy could end.

negative: Does subsidy work? Price elasticity of demand for influenza vaccination among the elderly in Japan Abstract Objectives Subsidy for influenza vaccination is often provided to the elderly in order to encourage them to receive a flu shot in developed countries. However, its effect on uptake rate, i.e., price elasticity of demand, has not been well studied. Methods Japan's decentralised vaccination programme allows observation of various pairs in price and uptake rate of flu shots among the elderly by the municipality from 2001/2002 to 2004/2005 season. We combine our sample survey data (n =281), which monitor price, subsidy and uptake rate, with published data on local characteristics in order to estimate price elasticity of demand with panel model. Results We find price elasticity of demand for influenza vaccine: nearly zero in nationwide, nearly zero in urban area, and −1.07 in rural area. Conclusions The results question the rationale for subsidy, especially in urban area. There are cases where maintaining or increasing the level of subsidy is not an efficient allocation of finite health care resources. When organising a vaccination programme, health manager should be careful about the balance between subsidy and other efforts in order to encourage the elderly to receive shots with price elasticity in mind.

negative: Incorporating Issues of Elderly Loneliness into the Coronavirus Disease–2019 Public Health Response As the systems that people depend on are increasingly strained by the coronavirus disease–2019 (COVID-19) outbreak, public health impacts are manifesting in different ways beyond morbidity and mortality for elderly populations. Loneliness is already a chief public health concern that is being made worse by COVID-19. Agencies should recognize the prevalence of loneliness among elderly populations and the impacts that their interventions have on loneliness. This letter describes several ways that loneliness can be addressed to build resilience for elderly populations as part of the public health response to COVID-19.

negative: COVID-19, Modern Pandemic: A Systematic Review From Front-Line Health Care Providers’ Perspective Coronavirus disease 2019 (COVID-19) caused infection in 168,000 cases worldwide in about 148 countries and killed more than 6,610 people around the world as of March 16, 2020, as per the World Health Organization (WHO). Compared to severe acute respiratory syndrome and Middle East respiratory syndrome, there is the rapid transmission, long incubation period, and disease containment is becoming extremely difficult. The main aim of this systematic review is to provide a comprehensive clinical summary of all the available data from high-quality research articles relevant to the epidemiology, demographics, trends in hospitalization and outcomes, clinical signs and symptoms, diagnostic methods and treatment methods of COVID-19, thus increasing awareness in health care providers. We also discussed various preventive measures to combat COVID-19 effectively. A systematic and protocol-driven approach is needed to contain this disease, which was declared as a global pandemic on March 11, 2020, by the WHO.

negative: Attenuation of influenza A virus disease severity by viral co-infection in a mouse model Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as co-pathogens within hosts. Clinical and epidemiological studies suggest that co-infection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other’s spread within a host population. To determine how co-infection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (RV1B) and mouse-adapted influenza A virus (PR8). Infection of mice with RV1B two days before PR8 reduced pathogenesis of mild to moderate, but not severe PR8 infections. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, co-infection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia or in vitro. Inflammation in co-infected mice remained focal, in comparison to diffuse inflammation and damage in the lungs of mice infected by PR8. These findings suggest that RV1B stimulates an early immune response that clears PR8 while limiting excessive pulmonary inflammation. The timing of RV1B co-infection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: co-infection by a murine coronavirus two days before PR8 also reduced disease severity. This model will be critical for understanding the mechanisms responsible for attenuation of influenza disease during co-infection by unrelated respiratory viruses.

negative: Corona Virus (COVID-19) “Infodemic” and Emerging Issues through a Data Lens: The Case of China Coronavirus (COVID-19) is a humanitarian emergency, which started in Wuhan in China in early December 2019, brought into the notice of the authorities in late December, early January 2020, and, after investigation, was declared as an emergency in the third week of January 2020. The WHO declared this as Public Health Emergency of International Concern (PHEIC) on 31th of January 2020, and finally a pandemic on 11th March 2020. As of March 24th, 2020, the virus has caused a casualty of over 16,600 people worldwide with more than 380,000 people confirmed as infected by it, of which more than 10,000 cases are serious. Mainly based on Chinese newspapers, social media and other digital platform data, this paper analyzes the timeline of the key actions taken by the government and people over three months in five different phases. It found that although there was an initial delay in responding, a unique combination of strong governance, strict regulation, strong community vigilance and citizen participation, and wise use of big data and digital technologies, were some of the key factors in China’s efforts to combat this virus. Being inviable and non-measurable (unlike radioactive exposure), appropriate and timely information is very important to form the basic foundation of mitigation and curative measures. Infodemic, as it is termed by WHO, is a key word, where different stakeholder’s participation, along with stricter regulation, is required to reduce the impact of fake news in this information age and social media. Although different countries will need different approaches, focusing on its humanitarian nature and addressing infodemic issues are the two critical factors for future global mitigation efforts.

negative: Impact of sex and gender on COVID-19 outcomes in Europe BACKGROUND: Emerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions. The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men. CONTENT: The present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging. Finally, we elucidate the impact of gender-specific lifestyle, health behavior, psychological stress, and socioeconomic conditions on COVID-19 and discuss sex specific aspects of antiviral therapies. CONCLUSION: The sex and gender disparities observed in COVID-19 vulnerability emphasize the need to better understand the impact of sex and gender on incidence and case fatality of the disease and to tailor treatment according to sex and gender. The ongoing and planned prophylactic and therapeutic treatment studies must include prospective sex- and gender-sensitive analyses.

negative: Health Behavior Education, e-research and a (H1N1) Influenza (Swine Flu): Bridging the Gap between Intentions and Health Behavior Change Abstract This study examined relations between risk perception/self-efficacy and handwashing intentions/behaviors during the A (H1N1) pandemic influenza. Data were collected from a longitudinal sample of Costa Ricans (NT1/T2 = 449/97). Results revealed that males and females presented a different social cognitive pattern in reaction to A (H1N1) pandemic. In females, the effects of risk perception/self-efficacy on handwashing behaviors were fully mediated by handwashing intentions. In males, self-efficacy influenced both directly and indirectly on handwashing behaviors, and risk perceptions showed no significant effect on handwashing behaviors. These results suggest that gender oriented protocols should be adopted by public health authorities in order to educate males and females in preventing both A (H1N1) and seasonal influenza.

negative: Smoking Cessation as a Public Health Measure to Limit the Coronavirus Disease 2019 Pandemic The novel coronavirus disease 2019 (COVID-19) has already evolved into a rapidly expanding pandemic. Risk factors for COVID-19, such as cardiovascular disease, chronic obstructive pulmonary disease and diabetes, are all strongly associated with smoking habits. The effects of cigarette smoking on the transmission of the virus and worsening of COVID-19 have been less addressed. Emerging data indicate that smoking history is the major determinant of worsening COVID-19 outcomes. Smoking cessation recovers airway ciliary clearance and immune function. Thus, smoking cessation awareness is strongly encouraged as a public health measure to limit the global impact of COVID-19.

negative: Prior Infections With Seasonal Influenza A/H1N1 Virus Reduced the Illness Severity and Epidemic Intensity of Pandemic H1N1 Influenza in Healthy Adults Background. A new influenza A/H1N1 (pH1N1) virus emerged in April 2009, proceeded to spread worldwide, and was designated as an influenza pandemic. A/H1N1 viruses had circulated in 1918–1957 and 1977–2009 and were in the annual vaccine during 1977–2009. Methods. Serum antibody to the pH1N1 and seasonal A/H1N1 viruses was measured in 579 healthy adults at enrollment (fall 2009) and after surveillance for illness (spring 2010). Subjects reporting with moderate to severe acute respiratory illness had illness and virus quantitation for 1 week; evaluations for missed illnesses were conducted over holiday periods and at the spring 2010 visit. Results. After excluding 66 subjects who received pH1N1 vaccine, 513 remained. Seventy-seven had reported with moderate to severe illnesses; 31 were infected with pH1N1 virus, and 30 with a rhinovirus. Determining etiology from clinical findings was not possible, but fever and prominent myalgias favored influenza and prominent rhinorrhea favored rhinovirus. Tests of fall and spring antibody indicated pH1N1 infection of 23% had occurred, with the rate decreasing with increasing anti-pH1N1 antibody; a similar pattern was seen for influenza-associated illness. A reducing frequency of pH1N1 infections was also seen with increasing antibody to the recent seasonal A/H1N1 virus (A/Brisbane/59/07). Preexisting antibody to pH1N1 virus, responses to a single vaccine dose, a low infection-to-illness ratio, and a short duration of illness and virus shedding among those with influenza indicated presence of considerable preexisting immunity to pH1N1 in the population. Conclusions. The 2009 A/H1N1 epidemic among healthy adults was relatively mild, most likely because of immunity from prior infections with A/H1N1 viruses.

negative: Management of COVID-19 Outbreak in Argentina: The Beginning The aim of this study was to analyze the impact coronavirus disease 2019 (COVID-19) had in Argentina during its initial stage, identify the measures taken to try to mitigate its impact, and briefly compare it with the influenza A H1N1 pandemic in 2009. This is a descriptive study. Pandemics constitute a serious problem to global health with a major impact on the affected countries’ populations. The recent COVID-19 outbreak represents one of the most important viral pandemics lately. It reached Argentina 64 days after the first case was identified in China. Since then, several measures were taken by the Argentinian government to try to mitigate its impact in this initial stage. An updated report of the current situation and its management in different countries is of vital importance regarding global health issues and may serve for feedback and decision-making.

negative: A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance BACKGROUND: Chickens are susceptible to infection with a limited number of Influenza A viruses and are a potential source of a human influenza pandemic. In particular, H5 and H7 haemagglutinin subtypes can evolve from low to highly pathogenic strains in gallinaceous poultry. Ducks on the other hand are a natural reservoir for these viruses and are able to withstand most avian influenza strains. RESULTS: Transcriptomic sequencing of lung and ileum tissue samples from birds infected with high (H5N1) and low (H5N2) pathogenic influenza viruses has allowed us to compare the early host response to these infections in both these species. Chickens (but not ducks) lack the intracellular receptor for viral ssRNA, RIG-I and the gene for an important RIG-I binding protein, RNF135. These differences in gene content partly explain the differences in host responses to low pathogenic and highly pathogenic avian influenza virus in chicken and ducks. We reveal very different patterns of expression of members of the interferon-induced transmembrane protein (IFITM) gene family in ducks and chickens. In ducks, IFITM1, 2 and 3 are strongly up regulated in response to highly pathogenic avian influenza, where little response is seen in chickens. Clustering of gene expression profiles suggests IFITM1 and 2 have an anti-viral response and IFITM3 may restrict avian influenza virus through cell membrane fusion. We also show, through molecular phylogenetic analyses, that avian IFITM1 and IFITM3 genes have been subject to both episodic and pervasive positive selection at specific codons. In particular, avian IFITM1 showed evidence of positive selection in the duck lineage at sites known to restrict influenza virus infection. CONCLUSIONS: Taken together these results support a model where the IFITM123 protein family and RIG-I all play a crucial role in the tolerance of ducks to highly pathogenic and low pathogenic strains of avian influenza viruses when compared to the chicken. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1778-8) contains supplementary material, which is available to authorized users.

negative: Pandemic Flu: Clinical management of patients with an influenza-like illness during an influenza pandemic

negative: Avian influenza – A review for doctors in travel medicine Summary First identified in humans in Hong Kong, influenza A/H5N1, known commonly as avian influenza, has caused human disease in 15 countries around the world. Although the current number of confirmed patients is tiny compared to seasonal and the recently emerged H1N1 ‘swine’ influenza, H5N1 remains a candidate for the next highly pathogenic influenza pandemic. Currently, H5N1 has very limited ability to spread from person-to-person but this may change because of mutation or reassortment with other influenza viruses leading to an influenza pandemic with high mortality. If this occurs travellers are likely to be affected and travel medicine doctors will need to consider avian influenza in returning febrile travellers. The early clinical features may be dismissed easily as ‘the flu’ resulting in delayed treatment. Treatment options are limited. Oral oseltamivir alone has been the most commonly used drug but mortality remains substantial, up to 80% in Indonesia. Intravenous peramivir has been filed for registration and IV zanamivir is being developed. This review will focus on the epidemiological and clinical features of influenza A/H5N1 avian influenza and will highlight aspects relevant to travel medicine doctors.

negative: Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens Pregnancy-associatedPlasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSA(PAM)) can be used in vitro to select parasites from nonpregnant donors to express VSA(PAM) and that this selection for VSA(PAM) expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA.

negative: A distinct name is needed for the new coronavirus

negative: Quantifying the annual incidence and underestimation of seasonal influenza: A modelling approach BACKGROUND: Seasonal influenza poses a significant public health and economic burden, associated with the outcome of infection and resulting complications. The true burden of the disease is difficult to capture due to the wide range of presentation, from asymptomatic cases to non-respiratory complications such as cardiovascular events, and its seasonal variability. An understanding of the magnitude of the true annual incidence of influenza is important to support prevention and control policy development and to evaluate the impact of preventative measures such as vaccination. METHODS: We use a dynamic disease transmission model, laboratory-confirmed influenza surveillance data, and randomized-controlled trial (RCT) data to quantify the underestimation factor, expansion factor, and symptomatic influenza illnesses in the US and Canada during the 2011-2012 and 2012-2013 influenza seasons. RESULTS: Based on 2 case definitions, we estimate between 0.42−3.2% and 0.33−1.2% of symptomatic influenza illnesses were laboratory-confirmed in Canada during the 2011-2012 and 2012-2013 seasons, respectively. In the US, we estimate between 0.08−0.61% and 0.07−0.33% of symptomatic influenza illnesses were laboratory-confirmed in the 2011-2012 and 2012-2013 seasons, respectively. We estimated the symptomatic influenza illnesses in Canada to be 0.32−2.4 million in 2011-2012 and 1.8−8.2 million in 2012-2013. In the US, we estimate the number of symptomatic influenza illnesses to be 4.4−34 million in 2011-2012 and 23−102 million in 2012-2013. CONCLUSIONS: We illustrate that monitoring a representative group within a population may aid in effectively modelling the transmission of infectious diseases such as influenza. In particular, the utilization of RCTs in models may enhance the accuracy of epidemiological parameter estimation.

negative: Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.

negative: What the growing rift between the US and WHO means for COVID-19 and global health.

negative: Burden of disease due to human coronavirus NL63 infections and periodicity of infection Abstract Background The disease burden caused by recently identified respiratory viruses like HCoV-NL63 is unknown. Objectives We determined the burden of disease due to HCoV-NL63 infections using the population-based PRI.DE cohort of children under the age of 3 with lower respiratory tract infections (LRTIs). Study design In total 1756 respiratory samples, from hospitalized children or children who visited the outpatient clinic, were tested for HCoV-NL63. Sampling covered a period of 2 years and the frequency of infection in different years was compared to other Western European studies that tested for this virus in 2 or more consecutive years. Results Sixty-nine samples were HCoV-NL63 positive, 35 were with high loads, and of these 25 were single HCoV-NL63 infections. Based on the number of children with high HCoV-NL63 infection and no additional infection, the overall annual incidence in outpatients was 7 per 1000 children per year (95% confidence interval (CI) 3–13 per 1000 children per year), which can be extrapolated to an absolute number of 16,929 visits to the physician due to an HCoV-NL63 infection in Germany per year. The estimated hospitalization rate is 22 per 100,000 children (95% CI: 7–49 per 100,000 children per year). This number reflects 522 HCoV-NL63 children in Germany per year. A large year-to-year difference in HCoV-NL63 infection frequency was observed. Combining these data with those of other studies in Western Europe revealed that HCoV-NL63 infections follow a 2-year inter-epidemic period with peaks of infection in the winters of 2000/2001, 2002/2003 and 2004/2005 (p <0.0001). Conclusions HCoV-NL63 infection in children below 3 years of age often requires a visit to the physician in an outpatient clinic, especially during peak-years, but hospitalizations are relatively infrequent.

negative: Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia Many respiratory viruses cocirculate in the population and multiple infections are commonly reported. The clinical impact of coinfection is unclear and may vary depending on the viral couples involved. Using three-dimensional reconstituted human airway epithelia and clinical viral strains, we investigated the interaction between influenza virus (Flu), respiratory syncytial virus (RSV) and rhinovirus (RV). We showed that Flu and RSV interfere with RV replication, whereas RV does not interfere with either of these viruses. We then experimentally demonstrated that, when present, the interference is not related to a block of viral entry but rather to type I and type III interferon (IFN), the front-line antiviral defense of the respiratory mucosa. Consistent with this observation, we highlighted the differential sensitivity of each virus to IFNs, with RV being the only virus significantly inhibited by IFN-λ and the most sensitive to IFN-α. Finally, as type III IFN is of therapeutic interest due to its low proinflammatory profile, we also assessed and confirmed an inhibitory effect of IFN-λ in the context of persistent RV infections. The present work provides mechanistic clues concerning innate immunity involvement during respiratory virus interactions and confirms that IFN-λ is a promising candidate in the treatment of RV infections.

negative: Oral mucosal lesions in a COVID-19 patient: new signs or secondary manifestations? Some oral manifestations have been observed in patients with coronavirus disease in 2019 (COVID-19). However, there is still a question about whether these lesions are due to coronavirus infection or secondary manifestations resulting from the patient's systemic condition. Thus, this article aims to report an additional case of the oral conditions in a patient diagnosed with COVID-19. Our patient, a sixty-seven-year-old Caucasian man, tested positive to coronavirus and presented oral manifestations such as recurrent herpes simplex, candidiasis, and geographic tongue. We support the argument that some oral conditions could be secondary to the deterioration of systemic health or due to treatments for COVID-19. The present case report highlights the importance of including dentists in the intensive care unit multi-professional team to improve oral health in critical patients not only COVID-19 patients. Also, to contribute to evidence-based and decision-making in managing infectious diseases.

negative: Pandemic influenza control in Europe and the constraints resulting from incoherent public health laws BACKGROUND: With the emergence of influenza H1N1v the world is facing its first 21(st )century global pandemic. Severe Acute Respiratory Syndrome (SARS) and avian influenza H5N1 prompted development of pandemic preparedness plans. National systems of public health law are essential for public health stewardship and for the implementation of public health policy[1]. International coherence will contribute to effective regional and global responses. However little research has been undertaken on how law works as a tool for disease control in Europe. With co-funding from the European Union, we investigated the extent to which laws across Europe support or constrain pandemic preparedness planning, and whether national differences are likely to constrain control efforts. METHODS: We undertook a survey of national public health laws across 32 European states using a questionnaire designed around a disease scenario based on pandemic influenza. Questionnaire results were reviewed in workshops, analysing how differences between national laws might support or hinder regional responses to pandemic influenza. Respondents examined the impact of national laws on the movements of information, goods, services and people across borders in a time of pandemic, the capacity for surveillance, case detection, case management and community control, the deployment of strategies of prevention, containment, mitigation and recovery and the identification of commonalities and disconnects across states. RESULTS: Results of this study show differences across Europe in the extent to which national pandemic policy and pandemic plans have been integrated with public health laws. We found significant differences in legislation and in the legitimacy of strategic plans. States differ in the range and the nature of intervention measures authorized by law, the extent to which borders could be closed to movement of persons and goods during a pandemic, and access to healthcare of non-resident persons. Some states propose use of emergency powers that might potentially override human rights protections while other states propose to limit interventions to those authorized by public health laws. CONCLUSION: These differences could create problems for European strategies if an evolving influenza pandemic results in more serious public health challenges or, indeed, if a novel disease other than influenza emerges with pandemic potential. There is insufficient understanding across Europe of the role and importance of law in pandemic planning. States need to build capacity in public health law to support disease prevention and control policies. Our research suggests that states would welcome further guidance from the EU on management of a pandemic, and guidance to assist in greater commonality of legal approaches across states.

negative: The World Health Organization and global health.

negative: Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2-14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3-4 days without truncation and at 5-9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.

negative: Globalized Perspectives on Infectious Disease Management and Trade in Africa: A Conceptual Framework for Assessing Risk in Developing Country Settings In the era of globalization, internationalized representations of infectious disease threats have profound implications for understandings of infectious disease problems and their management in developing countries, particularly in Sub-Saharan Africa. By examining the policy implications of the key narratives around public health, animal health and trade, it becomes possible to clarify the relationship between global understandings of infectious disease risk and their impact on the development of local responses to disease problems. We highlight the tensions that resource-constrained countries face in the nexus of animal health-public health and trade, including the perception that resource-constrained countries are both source and victims of potential infectious disease threats. Given this scenario, it is important to think about how developing countries, particularly those in Sub-Saharan Africa, can approach infectious disease risk management as it relates to pandemic scale threats such as avian and pandemic influenza. We outline some of the key considerations in defining and assessing disease risk using avian and pandemic influenza in Zambia as an example. We conclude that the key to the feasibility of the analysis of the risk of multi-sectoral affecting emerging infectious diseases such as zoonotic avian influenza is flexibility in how risk is framed across the public health, animal health and trade systems.

negative: Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients. INTRODUCTION Chronic hemodialysis (HD) patients are considered to be at high risk for infection. Here, we describe the clinical outcomes of chronic HD patients with influenza A (H1N1) infection and the strategies adopted to control an outbreak of influenza A in a dialysis unit. METHODS Among a total of 62 chronic HD patients, H1N1 infection was identified in 12 (19.4%). Of the 32 staff members, four (12.5%) were found to be infected with the H1N1 virus. Outcomes included symptoms at presentation, comorbidities, occurrence of hypoxemia, hospital admission, and clinical evaluation. Infection was confirmed by real-time reverse transcriptase polymerase chain reaction. RESULTS The 12 patients who had H1N1 infection did not differ significantly from the other 50 non-infected patients with respect to age, sex, dialysis vintage, dialysis modality, or proportion of comorbidities. Obesity was higher in the H1N1-infected group (41.5 vs. 4%, p<0.002). The most common symptoms were fever (92%), cough (92%), and rhinorrhea (83%). Early empirical antiviral treatment with oseltamivir was started in symptomatic patients and infection control measures, including the intensification of contact-reduction measures by the staff members, antiviral chemoprophylaxis to asymptomatic patients undergoing HD in the same shift of infected patients, and dismiss of staff members suspected of being infected, were implemented to control the spread of infection in the dialysis unit. CONCLUSION The clinical course of infection with H1N1 in our patients was favorable. None of the patients developed severe disease and the strategies adopted to control the outbreak were successful.

negative: Viral Etiology of Acute Respiratory Infection in Gansu Province, China, 2011 BACKGROUND: Acute respiratory infections (ARIs) are the leading cause of children and their leading killer. ARIs are responsible for at least six percent of the world's disability and death. Viruses are one of the most common agents causing ARIs. Few studies on the viral etiology and clinical characteristics of ARIs have been performed in the northwest region of China, including Gansu Province. METHODS: Clinical and demographic information and throat swabs were collected from 279 patients from January 1st to December 30st, 2011. Multiplex RT-PCR was performed to detect 16 respiratory viral pathogens. RESULTS: 279 patients were admitted for ARIs. The patients aged from 1 month to 12 years, with the median age of 2 years. Of which, 105 (37.6%) were positive for at least one pathogen. A total of 136 respiratory viral pathogens were identified from the 105 patients. Respiratory syncytial virus (RSV) was the most frequently detected pathogen (26.5%, 36/136), followed by parainfluenza virus (PIV) 1–3 (22.1%, 30/136), human rhinovirus (HRV) (21.3%, 29/136), human coronavirus (CoV) (10.3%, 14/136) and human adenovirus (HAdV) (9.6%, 13/136). Influenza A (Flu A), human metapneumovirus (hMPV) and human bocavirus (BoCA) were found 4.4%, 3.7% and 2.2%, respectively. Influenza B (Flu B) and seasonal influenza A H1N1(sH1N1) were not detected. Single-infections were detected in 30.5% (85/279) of cases. RSV was the most common pathogens in patients under 1 year and showed seasonal variation with peaks during winter and spring. CONCLUSIONS: This paper presents data on the epidemiology of viral pathogens associated with ARIs among children in Gansu Province, China. RSV is most frequently detected in our study. The findings could serve as a reference for local CDC in drawing up further plans to prevent and control ARIs.

negative: 16 Pandemic Influenza Abstract This chapter will describe pandemic threats and the steps necessary to reduce morbidity and mortality. An explanation is provided on genetic mutations leading to the emergence of novel influenza strains. Medical countermeasures include vaccination and antiviral medications. Public messaging is also important to promote flu shots, reinforce basic hygiene measures, and instruct those who may be ill to limit contacts. The World Health Organization (WHO) tracks seasonal influenza for anomalies indicating an emerging pandemic influenza strain. WHO updated the international pandemic alert system after the 2009–2010 H1N1 pandemic. With each declaration, temporary recommendations are provided, and added regulatory actions are taken by WHO member states. In addition, the Centers for Disease Control and Prevention (CDC) updated the U.S. framework for pandemic influenza preparedness and response. Each pandemic interval is accompanied by specific recommendations for state and local public health authorities. Effective influenza control includes both pharmaceutical and nonpharmaceutical recommendations. Other severe viral pandemic respiratory threats, including the “Middle East Respiratory Syndrome Coronavirus” (MERS-CoV), require similar resources and infrastructure to manage.

negative: The "influenza vaccine" – benefit, risk, costs More than 20 million people died during the pandemic 'flu season 1918/1919, the largest influenza pandemic of the 20th century. Since then, influenza A virus infections have been known as a serious cause of morbidity and mortality in the whole world population. Although specific and effective antiviral therapeutics (neuraminidase inhibitors) are available, vaccinating against influenza is the first preventative measure. In Germany, influenza immunization has been yearly recommended by the current vaccination committee of the Robert Koch Institute (STIKO). Vaccinations have a special indication in elderly persons >60 years, patients with chronic diseases and persons with higher risk of influenza infections. In general, inactivated vaccines are well tolerated by recipients. The cost effectiveness of influenza vaccination has been well established. Although the benefit of annual influenza vaccination especially for the elderly and risk groups is beyond doubt, a low acceptance of vaccine recommendations has been noticed in Germany to date.

negative: COVID-19 diagnosis and management: a comprehensive review Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a novel coronavirus from the same family as SARS-CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), presents flu-like symptoms which can become serious in high-risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID-19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: 'COVID-19', '2019-nCoV', 'coronavirus' and 'SARS-CoV-2'. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID-19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real-time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow-up. To date, there is no evidence of any effective treatment for COVID-19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence-based treatment modality.

negative: Efficacy and safety of Echinaforce® in respiratory tract infections Echinaforce® is the standardised extract of Echinacea purpurea from Bioforce, Switzerland. Recent studies show immunomodulation and broad antiviral effects against respiratory tract viruses. Haemagglutinin and Neuraminidase are blocked. In contrast to Oseltamivir no resistance is caused by Echinaforce®. A randomised, double-blind, placebo-controlled study over four months confirms that Echinaforce® supports the immune resistance and acts directly against a series of viruses. Echinaforce® is efficacious and safe in respiratory tract infections for long-term and short-term prevention as well as for acute treatment.

negative: Burden, seasonal pattern and symptomatology of acute respiratory illnesses with different viral aetiologies in children presenting at outpatient clinics in Hong Kong Abstract Respiratory viruses cause acute respiratory diseases with a broad and overlapping spectrum of symptoms. We examined the clinical symptoms and explored the patterns of various respiratory viral infections in children in Hong Kong. Among 2090 specimens collected from outpatient care (2007–2010), 1343 (64.3%) were positive for any virus by the xTAG assay, and 81 (3.9%) were positive for co-infection. The most frequently detected viruses among children aged 6–15 years were enterovirus/rhinovirus and influenza virus A, whereas most non-influenza viruses were more frequently detected in younger children. Higher body temperature was more common for illnesses associated with influenza viruses than for those associated with non-influenza viruses, but other symptoms were largely similar across all infections. The seasonality pattern varied among different viruses, with influenza virus A being the predominant virus detected in winter, and enterovirus/rhinovirus being more commonly detected than influenza virus A in the other three seasons, except for 2009.

negative: Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System Human coronaviruses (HCoV) are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43). In an attempt to study the role of this protein in virus spread within the central nervous system (CNS) and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G (758) to RRSR↓R (758)), which introduces a putative furin-like cleavage (↓) site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies.

negative: Impact of climate and public health interventions on the COVID-19 pandemic: A prospective cohort study. BACKGROUND It is unclear whether seasonal changes, school closures or other public health interventions will result in a slowdown of the current coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine whether epidemic growth is globally associated with climate or public health interventions intended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS We performed a prospective cohort study of all 144 geopolitical areas worldwide (375 609 cases) with at least 10 COVID-19 cases and local transmission by Mar. 20, 2020, excluding China, South Korea, Iran and Italy. Using weighted random-effects regression, we determined the association between epidemic growth (expressed as ratios of rate ratios [RRR] comparing cumulative counts of COVID-19 cases on Mar. 27, 2020, with cumulative counts on Mar. 20, 2020) and latitude, temperature, humidity, school closures, restrictions of mass gatherings, and measures of social distancing during an exposure period 14 days previously (Mar. 7 to 13, 2020). RESULTS In univariate analyses, there were few or no associations of epidemic growth with latitude and temperature, but weak negative associations with relative humidity (RRR per 10% 0.91, 95% confidence interval [CI] 0.85-0.96) and absolute humidity (RRR per 5 g/m3 0.92, 95% CI 0.85-0.99). Strong associations were found for restrictions of mass gatherings (RRR 0.65, 95% CI 0.53-0.79), school closures (RRR 0.63, 95% CI 0.52-0.78) and measures of social distancing (RRR 0.62, 95% CI 0.45-0.85). In a multivariable model, there was a strong association with the number of implemented public health interventions (p for trend = 0.001), whereas the association with absolute humidity was no longer significant. INTERPRETATION Epidemic growth of COVID-19 was not associated with latitude and temperature, but may be associated weakly with relative or absolute humidity. Conversely, public health interventions were strongly associated with reduced epidemic growth.

negative: Detecting early‐warning signals of influenza outbreak based on dynamic network marker The seasonal outbreaks of influenza infection cause globally respiratory illness, or even death in all age groups. Given early‐warning signals preceding the influenza outbreak, timely intervention such as vaccination and isolation management effectively decrease the morbidity. However, it is usually a difficult task to achieve the real‐time prediction of influenza outbreak due to its complexity intertwining both biological systems and social systems. By exploring rich dynamical and high‐dimensional information, our dynamic network marker/biomarker (DNM/DNB) method opens a new way to identify the tipping point prior to the catastrophic transition into an influenza pandemics. In order to detect the early‐warning signals before the influenza outbreak by applying DNM method, the historical information of clinic hospitalization caused by influenza infection between years 2009 and 2016 were extracted and assembled from public records of Tokyo and Hokkaido, Japan. The early‐warning signal, with an average of 4‐week window lead prior to each seasonal outbreak of influenza, was provided by DNM‐based on the hospitalization records, providing an opportunity to apply proactive strategies to prevent or delay the onset of influenza outbreak. Moreover, the study on the dynamical changes of hospitalization in local district networks unveils the influenza transmission dynamics or landscape in network level.

negative: Viral etiology of acute respiratory infections in hospitalized children in Novosibirsk City, Russia (2013 – 2017) BACKGROUND: Acute respiratory infections (ARIs) cause a considerable morbidity and mortality worldwide especially in children. However, there are few studies of the etiological structure of ARIs in Russia. In this work, we analyzed the etiology of ARIs in children (0–15 years old) admitted to Novosibirsk Children’s Municipal Clinical Hospital in 2013–2017. METHODS: We tested nasal and throat swabs of 1560 children with upper or lower respiratory infection for main respiratory viruses (influenza viruses A and B, parainfluenza virus types 1–4, respiratory syncytial virus, metapneumovirus, four human coronaviruses, rhinovirus, adenovirus and bocavirus) using a RT-PCR Kit. RESULTS: We detected 1128 (72.3%) samples were positive for at least one virus. The most frequently detected pathogens were respiratory syncytial virus (358/1560, 23.0%), influenza virus (344/1560, 22.1%), and rhinovirus (235/1560, 15.1%). Viral co-infections were found in 163 out of the 1128 (14.5%) positive samples. We detected significant decrease of the respiratory syncytial virus-infection incidence in children with increasing age, while the reverse relationship was observed for influenza viruses. CONCLUSIONS: We evaluated the distribution of respiratory viruses in children with ARIs and showed the prevalence of respiratory syncytial virus and influenza virus in the etiological structure of infections. This study is important for the improvement and optimization of diagnostic tactics, control and prevention of the respiratory viral infections.

negative: Forecasting influenza epidemics by integrating internet search queries and traditional surveillance data with the support vector machine regression model in Liaoning, from 2011 to 2015 BACKGROUND: Influenza epidemics pose significant social and economic challenges in China. Internet search query data have been identified as a valuable source for the detection of emerging influenza epidemics. However, the selection of the search queries and the adoption of prediction methods are crucial challenges when it comes to improving predictions. The purpose of this study was to explore the application of the Support Vector Machine (SVM) regression model in merging search engine query data and traditional influenza data. METHODS: The official monthly reported number of influenza cases in Liaoning province in China was acquired from the China National Scientific Data Center for Public Health from January 2011 to December 2015. Based on Baidu Index, a publicly available search engine database, search queries potentially related to influenza over the corresponding period were identified. An SVM regression model was built to be used for predictions, and the choice of three parameters (C, γ, ε) in the SVM regression model was determined by leave-one-out cross-validation (LOOCV) during the model construction process. The model’s performance was evaluated by the evaluation metrics including Root Mean Square Error, Root Mean Square Percentage Error and Mean Absolute Percentage Error. RESULTS: In total, 17 search queries related to influenza were generated through the initial query selection approach and were adopted to construct the SVM regression model, including nine queries in the same month, three queries at a lag of one month, one query at a lag of two months and four queries at a lag of three months. The SVM model performed well when with the parameters (C = 2, γ = 0.005, ɛ = 0.0001), based on the ensemble data integrating the influenza surveillance data and Baidu search query data. CONCLUSIONS: The results demonstrated the feasibility of using internet search engine query data as the complementary data source for influenza surveillance and the efficiency of SVM regression model in tracking the influenza epidemics in Liaoning.

negative: Interim results: state-specific seasonal influenza vaccination coverage - United States, August 2009-January 2010. The advent of the 2009 influenza A (H1N1) pandemic in April 2009 made the 2009-10 influenza season highly unusual. Public awareness of the potential seriousness of influenza was heightened by media coverage of pandemic-associated hospitalizations and deaths, especially among younger persons. In the fall, the distribution of two separate influenza vaccines began, with distinct, although overlapping, recommendations from the Advisory Committee on Immunization Practices (ACIP). In addition, 2009-10 was the first full season in which ACIP's recommendation to vaccinate all children aged 5--18 years was implemented. To provide preliminary state-specific estimates of seasonal influenza vaccination coverage, CDC analyzed Behavioral Risk Factor Surveillance System (BRFSS) and National 2009 H1N1 Flu Survey (NHFS) data collected during October 2009-February 2010. By January 31, estimated state seasonal influenza vaccination coverage among persons aged >or=6 months ranged from 30.3% to 54.5% (median: 40.6%). Median coverage was 41.2% for children aged 6 months-17 years, 38.3% for adults aged 18--49 years with high-risk conditions, 28.8% for adults aged 18-49 years without high-risk conditions, 45.5% for adults aged 50-64 years, and 69.3% for adults aged >or=65 years. These results, compared with the previous season, suggest large increases in coverage for children and a moderate increase for adults aged 18-49 years without high-risk conditions. Health departments should identify best practices that lead to higher vaccination coverage and should support effective vaccination services (e.g., school-located vaccination programs and office-based protocols, such as reminder/recall and standing orders).

negative: The traps of calling the public health response to COVID-19 “an unexpected war against an invisible enemy”

negative: Occupational Health Science in the Time of COVID-19: Now more than Ever Workers bear a heavy share of the burden of how countries contend with COVID-19; they face numerous serious threats to their occupational health ranging from those associated with direct exposure to the virus to those reflecting the conflicts between work and family demands. Ten experts were invited to comment on occupational health issues unique to their areas of expertise. The topics include work-family issues, occupational health issues faced by emergency medical personnel, the transition to telework, discrimination against Asian-Americans, work stressors, presenteeism, the need for supportive supervision, safety concerns, economic stressors, and reminders of death at work. Their comments describe the nature of the occupational health concerns created by COVID-19 and discuss both unanswered research questions and recommendations to help organizations reduce the impacts of COVID-19 on workers.

negative: Estimating Infection Attack Rates and Severity in Real Time during an Influenza Pandemic: Analysis of Serial Cross-Sectional Serologic Surveillance Data BACKGROUND: In an emerging influenza pandemic, estimating severity (the probability of a severe outcome, such as hospitalization, if infected) is a public health priority. As many influenza infections are subclinical, sero-surveillance is needed to allow reliable real-time estimates of infection attack rate (IAR) and severity. METHODS AND FINDINGS: We tested 14,766 sera collected during the first wave of the 2009 pandemic in Hong Kong using viral microneutralization. We estimated IAR and infection-hospitalization probability (IHP) from the serial cross-sectional serologic data and hospitalization data. Had our serologic data been available weekly in real time, we would have obtained reliable IHP estimates 1 wk after, 1–2 wk before, and 3 wk after epidemic peak for individuals aged 5–14 y, 15–29 y, and 30–59 y. The ratio of IAR to pre-existing seroprevalence, which decreased with age, was a major determinant for the timeliness of reliable estimates. If we began sero-surveillance 3 wk after community transmission was confirmed, with 150, 350, and 500 specimens per week for individuals aged 5–14 y, 15–19 y, and 20–29 y, respectively, we would have obtained reliable IHP estimates for these age groups 4 wk before the peak. For 30–59 y olds, even 800 specimens per week would not have generated reliable estimates until the peak because the ratio of IAR to pre-existing seroprevalence for this age group was low. The performance of serial cross-sectional sero-surveillance substantially deteriorates if test specificity is not near 100% or pre-existing seroprevalence is not near zero. These potential limitations could be mitigated by choosing a higher titer cutoff for seropositivity. If the epidemic doubling time is longer than 6 d, then serial cross-sectional sero-surveillance with 300 specimens per week would yield reliable estimates when IAR reaches around 6%–10%. CONCLUSIONS: Serial cross-sectional serologic data together with clinical surveillance data can allow reliable real-time estimates of IAR and severity in an emerging pandemic. Sero-surveillance for pandemics should be considered. Please see later in the article for the Editors' Summary

negative: Emerging Influenza and Psychosis: An Important Story in Psychological Medicine

negative: Predictions and measurements of the stack effect on indoor airborne virus transmission in a high-rise hospital building Abstract As the viral diseases such as Severe Acute Respiratory Syndrome (SARS) and Influenza A (H1N1) occur in many countries recently, the epidemic of those influenza viruses causes many human casualties. Moreover, the second infection from infected patients particularly within general hospitals frequently takes places due to improperly hospitalized and/or quarantined patients. Accordingly, it becomes a great concern to accommodate safer ventilation system in general hospital wards against such airborne transmitted viruses. It is also a recent trend that many urban general hospitals are designed and constructed as high-rises. If a virus is transmitted through uncontrolled air movement within a hospital and then infected other patients or healthy visitors, it might be impossible to control the spread of the disease. Thus research has been preceded scrutinizing stack effect on the indoor airborne virus transmission in large hospitals by conducting both the field measurement and numerical analysis according to the outdoor temperature and the releasing vertical points of the tracer gas assumed as a viral contaminant. In the field measurement of a high-rise hospital, the indoor airflow was affected by the stack effect of vertical chute of the building. The numerical simulation was verified by comparing its prediction results and the field measurement data. In result, very high possibility has witnessed that the airborne contaminant emitted from the infected patients in the lower floors could be transported to the higher floors through the airflow driven by the stack effect.

negative: Avian flu (H5N1): its epidemiology, prevention, and implications for anesthesiology Abstract Avian flu, influenza A subtype H5N1, is an emergent and virulent disease that poses a threat to the health and safety of the world community. Avian flu is 1 of more than 25 influenza A viruses that reside primarily in birds but also infect humans and other mammals. Avian flu is responsible for the current outbreak in Asia; H5N1 has now displayed probable human-to-human transmission; it could be a harbinger of a global epidemic. Anesthesiologists are exposed to a risk for infection when they are involved in airway instrumentation of infected patients. Given the evidence of emerging resistance to common antiviral agents used to treat H5N1 influenza virus and limited supply of H5N1 vaccine, prevention is our best protection. The following article will detail the virology and preventive public health practices for H5N1. This knowledge can also be used to define and prevent other yet unidentified infectious threats.

negative: An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV) was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV) HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health.

negative: Custom-made vaccines at speed The concept of reverse genetics has enabled researchers to construct an experimental vaccine against a potential pandemic influenza strain in less than a month.

negative: Environments, Behaviors, and Inequalities: Reflecting on the Impacts of the Influenza and Coronavirus Pandemics in the United States In the past century, dramatic shifts in demographics, globalization and urbanization have facilitated the rapid spread and transmission of infectious diseases across continents and countries. In a matter of weeks, the 2019 coronavirus pandemic devastated communities worldwide and reinforced the human perception of frailty and mortality. Even though the end of this pandemic story has yet to unfold, there is one parallel that is undeniable when a comparison is drawn between the 2019 coronavirus and the 1918 influenza pandemics. The public health response to disease outbreaks has remained nearly unchanged in the last 101 years. Furthermore, the role of environments and human behaviors on the effect and response to the coronavirus pandemic has brought to light many of the historic and contemporaneous inequalities and injustices that plague the United States. Through a reflection of these pandemic experiences, the American burden of disparity and disproportionality on morbidity, mortality and overall social determinants of health has been examined. Finally, a reimagination of a post-coronavirus existence has also been presented along with a discussion of possible solutions and considerations for moving forward to a new and better normal.

negative: The association between age, COVID-19 symptoms, and social distancing behavior in the United States BACKGROUND: Public health authorities recommend that people practice social distancing, especially if they have symptoms of coronavirus disease (COVID-19), or are older and more at risk of serious illness if they become infected. We test the hypothesis that these groups are following these recommendations and are more likely to undertake social distancing. METHODS: We conducted an open online survey of 4,676 U.S. adults aged 18 and older between April 4 and April 7, 2020. We model the effects of age and common COVID-19 symptoms in the last two weeks on going out of the home for non-healthcare reasons the day before taking the survey, using a logistic model and the number of close contacts (within 6 feet) that respondents had with non-household members, using a Poisson count model. Our models control for several covariates, including other flu-like symptoms, sex, education, income, whether the respondent worked in February, household size, population density in the respondent’s ZIP code, state fixed effects, and the day of completion of the survey. We also weight our analyses to make the sample representative of the U.S. adult population. FINDINGS: About 52 percent of the adult United States population went out of their home the previous day. On average, adults had close contact with 1.9 non-household members. We find that having at least one COVID-19 symptom (fever, dry cough, or shortness of breath) increased the likelihood of going out the previous day and having additional close contacts with non-household members; however, the estimates were not statistically significant. When disaggregating our analysis by COVID-19 symptoms, we find no strong evidence of greater social distancing by people with a fever or cough in the last two weeks, but we do find that those who experienced shortness of breath have fewer close contacts, with an incidence rate ratio (IRR) of 0.49 (95% CI: 0.30–0.78). Having other flu-like symptoms reduces the odds of going out by 0.32 (95% CI: 0.18–0.60) and the incidence rate of having close contacts by 42 percent (IRR = 0.58; 95% CI: 0.38–0.88). We find that older people are just as likely to leave their homes as younger people, but people over the age of 50 had less than half the predicted number of close contacts than those who were younger than 30. Our approach has the limitation that the survey sample is self-selected. Our findings may therefore be subject to selection bias that is not adequately controlled for by weighting. In addition, the possibility exists of confounding of the results due to omitted variable bias. CONCLUSIONS: We provide evidence that older people are having significantly fewer close contacts than younger people, which is in line with the public health authorities’ recommendations. We also find that people experiencing shortness of breath are practicing more intense social distancing. However, we find that those with two other common COVID-19 symptoms, fever and dry cough, are not engaging in greater social distancing, suggesting that increased targeting on relevant symptoms, and messaging, may be required.

negative: Aeromonas salmonicida Infection Only Moderately Regulates Expression of Factors Contributing to Toll-Like Receptor Signaling but Massively Activates the Cellular and Humoral Branches of Innate Immunity in Rainbow Trout (Oncorhynchus mykiss) Toll-like receptors (TLRs) are known to detect a defined spectrum of microbial structures. However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far. We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss. Intraperitoneal injection of a lethal dose of Aeromonas salmonicida subsp. salmonicida induced highly increased levels of cytokine mRNAs during a 72-hour postinfection (hpi) period. In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased. Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells. T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney. In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida. The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.

negative: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.

negative: Excess mortality during COVID-19 in five European countries and a critique of mortality analysis data INTRODUCTION The COVID-19 pandemic is an ongoing event disrupting lives, health systems, and economies worldwide. Clear data about the pandemic's impact is lacking, namely regarding mortality. This work aims to study the impact of COVID-19 through the analysis of all-cause mortality data made available by different European countries, and to critique their mortality surveillance data. METHODS European countries that had publicly available data about the number of deaths per day/week were selected (England and Wales, France, Italy, Netherlands and Portugal). Two different methods were selected to estimate the excess mortality due to COVID19: (DEV) deviation from the expected value from homologue periods, and (RSTS) remainder after seasonal time series decomposition. We estimate total, age- and gender-specific excess mortality. Furthermore, we compare different policy responses to COVID-19. RESULTS Excess mortality was found in all 5 countries, ranging from 10.6% in Portugal (DEV) to 98.5% in Italy (DEV). Furthermore, excess mortality is higher than COVID-attributed deaths in all 5 countries. DISCUSSION The impact of COVID-19 on mortality appears to be larger than officially attributed deaths, in varying degrees in different countries. Comparisons between countries would be useful, but large disparities in mortality surveillance data could not be overcome. Unreliable data, and even a lack of cause-specific mortality data undermine the understanding of the impact of policy choices on both direct and indirect deaths during COVID-19. European countries should invest more on mortality surveillance systems to improve the publicly available data.

negative: C&EN talks with Holden Thorp When Holden Thorp became editor in chief of Science in October 2019, he wasn’t planning to write editorials challenging the US president during an international crisis But as the current pandemic began to unfold, Thorp was triggered by President Donald J Trump’s inaccurate comparisons of COVID-19—the disease caused by the novel coronavirus, SARS-CoV-2—to the flu and the unrealistic expectations he put on vaccine developers and pharmaceutical companies Thorp and his editorial team felt that Trump’s denial of what scientists had been saying “was just so dangerous that we wouldn’t be doing our job if we didn’t speak out,” he says And so he has, by writing a series of editorials about the role of science in addressing the pandemic One of the editorials was widely circulated and cited in the Washington Post and the New York Times—not common for an editorial in a research journal Thorp hopes that the editorials

negative: Comparison of clinical outcomes of influenza A and B at the 2017–2018 influenza season: a cohort study Influenza has significant morbidity and mortality. Some experts consider infection with influenza B as milder than that with influenza A. The objective of this study is to evaluate the outcomes of hospitalized patients with laboratory-confirmed influenza A or B in 2017–2018 influenza season. All hospitalized patients between October 2017 and April 2018 with laboratory-confirmed influenza A and B were included. The primary composite outcomes were pneumonia/myocarditis/encephalitis, mechanical ventilation, ICU admission, and 30-day mortality. Secondary outcomes were 30-/90-day mortality, length of hospital stay, and readmission rates. The study included 201 influenza A and 325 influenza B. For the primary composite outcome, no significant difference was demonstrated between influenza A and B. Rates of mortality were similar at 30 and 90 days. Influenza A had higher pneumonia rates and mechanical ventilation. On multivariate analysis, higher Charlson’s score, hypoalbuminemia, and vasopressor use were associated with 30-day mortality, while infection with either influenza A or B was not. Influenza A was associated with higher pneumonia and mechanical ventilation rates. However, influenza B resulted with similar 30-day mortality rate as influenza A.

negative: COVID-19: An Update on the Epidemiological, Genomic Origin, Phylogenetic study, India centric to Worldwide current status The pandemic spread of novel coronavirus, (SARS-CoV-2) causing CoronaVirus Infectious Diseases (COVID-19) emerged into a global threat for human life causing serious death rates and economic crunch all over the globe. As on April 17, 2020 at 2:00am CEST, there include a total of 2,034,802 confirmed cases for Corona and 1,35,163 deaths worldwide have been reported which includes 212 countries, areas or territories reported by World Health Organization (WHO), in which USA tops 6,32,781 confirmed cases (28,221 deaths) followed by Italy 1,65,155 (21,647 deaths), Spain 1,77,633 (18,579 deaths) and China 84,149 (4,642 deaths). This study aims to compare the genomic nature of SARS-CoV-2 genome reported from Wuhan, China with two Indian isolate genome reported by ICMR-NIV, India. Further Phylogenetic studies performed with coronavirus infecting non-human species like Bats, Duck, and sparrow were compared with Indian and other country whole genome sequences of SARS-CoV2 using MegaX and traced out the association between the human coronavirus with the other species viral genome. In addition, epidemiological reports on COVID-19 among Worldwide and India centric data were compared between April 7, 2020 to April 17, 2020 global data and the number of active cases were increased dramatically in this 10 days period studied, highlighted in the current study.

negative: Genomic variance of the 2019‐nCoV coronavirus There is a rising global concern for the recently emerged novel coronavirus (2019‐nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019‐nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019‐nCoV. Despite the low heterogeneity of the 2019‐nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8‐encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti‐coronavirus approaches.

negative: Does communicable diseases (including COVID-19) may increase global poverty risk? A cloud on the horizon Coronavirus epidemic can push millions of people in poverty. The shortage of healthcare resources, lack of sanitation, and population compactness leads to an increase in communicable diseases, which may increase millions of people add in a vicious cycle of poverty. The study used the number of factors that affect poverty incidence in a panel of 76 countries for a period of 2010–2019. The dynamic panel GMM estimates show that the causes of death by communicable diseases, chemical-induced carbon and fossil fuel combustion, and lack of access to basic hand washing facilities menace to increase poverty headcounts, whereas, an increase in healthcare expenditures substantially decreases poverty headcounts across countries. Further, the results show the U-shaped relationship between economic growth and poverty headcounts, as economic growth first decreases and later increase poverty headcount due to rising healthcare disparities among nations. The causality estimates show that lack of access to basic amenities lead to increase of communicable diseases including COVID-19 whereas chemical-induced carbon and fossil fuel emissions continue to increase healthcare expenditures and economic growth in a panel of selected countries. The rising healthcare disparities, regional conflicts, and public debt burden further ‘hold in the hand’ of communicable diseases that push millions of people in the poverty trap.

negative: Using patient-collected clinical samples and sera to detect and quantify the severe acute respiratory syndrome coronavirus (SARS-CoV) BACKGROUND: Severe acute respiratory syndrome (SARS) caused a large outbreak of pneumonia in Beijing, China, in 2003. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect and quantify SARS-CoV in 934 sera and self-collected throat washes and fecal samples from 271 patients with laboratory-confirmed SARS managed at a single institution. RESULTS: SARS-CoV detection rates in sera were highest in the first 9 days of illness, whereas detection was highest in throat washes 5–14 days after onset of symptoms. The highest SARS-CoV RT-PCR rates (70.4–86.3%) and viral loads (log(10 )4.5–6.1) were seen in fecal samples collected 2–4 weeks after the onset of clinical illness. Fecal samples were frequently SARS-CoV RT-PCR positive beyond 40 days, and occasional sera still had SARS-CoV detected after 3 weeks of illness. CONCLUSION: In the context of an extensive outbreak with major pressure on hospital resources, patient self-collected samples are an alternative to nasopharyngeal aspirates for laboratory confirmation of SARS-CoV infection.

negative: Development of a Rapid Automated Influenza A, Influenza B, and Respiratory Syncytial Virus A/B Multiplex Real-Time RT-PCR Assay and Its Use during the 2009 H1N1 Swine-Origin Influenza Virus Epidemic in Milwaukee, Wisconsin Rapid, semiautomated, and fully automated multiplex real-time RT-PCR assays were developed and validated for the detection of influenza (Flu) A, Flu B, and respiratory syncytial virus (RSV) from nasopharyngeal specimens. The assays can detect human H1N1, H3N2, and swine-origin (S-OIV) H1N1 Flu A viruses and were effectively used to distinguish Flu A infections (of all subtypes) from Flu B and RSV infections during the current S-OIV outbreak in Milwaukee, WI. The analytical limits of detection were 10(−2) to 10(1) TCID(50)/ml depending on the platform and analyte and showed only one minor cross-reaction among 23 common respiratory pathogens (intermittent cross-reaction to adenovirus at >10(7) TCID(50)/ml). A total of 100 clinical samples were tested by tissue culture, both automated assays, and the US Food and Drug Administration-approved ProFlu+ assay. Both the semiautomated and fully automated assays exhibited greater overall (Flu A, Flu B, and RSV combined) clinical sensitivities (93 and 96%, respectively) and individual Flu A sensitivities (100%) than the Food and Drug Administration-approved test (89% overall sensitivity and 93% Flu A sensitivity). All assays were 99% specific. During the S-OIV outbreak in Milwaukee, WI, the fully automated assay was used to test 1232 samples in 2 weeks. Flu A was detected in 134 clinical samples (126 H1N1 S-OIV, 5 H1N1 [human], and 1 untyped) with 100% positive agreement compared with other “in-house” validated molecular assays, with only 2 false-positive results. Such accurate testing using automated high-throughput molecule systems should allow clinicians and public health officials to react quickly and effectively during viral outbreaks.

negative: Pandemic Influenza Vaccines Since their compositions remain uncertain, universal pandemic vaccines are yet to be created. They would aim to protect globally against pandemic influenza viruses that have not yet evolved. Thus they differ from seasonal vaccines to influenza virus, which are updated annually in spring to incorporate the latest circulating viruses, and are then produced and delivered before the peak influenza season starts in late fall and winter. The efficacy of seasonal vaccines is linked to their ability to induce virus-neutralizing antibodies, which provide subtype-specific protection against influenza A viruses. If pandemic vaccines were designed to resemble current vaccines in terms of composition and mode of action, they would have to be developed, tested, and mass-produced after the onset of a pandemic, once the causative virus had been identified. The logistic problems of generating a pandemic vaccine from scratch, conducting preclinical testing, and producing billions of doses within a few months for global distribution are enormous and may well be insurmountable. Alternatively, the scientific community could step up efforts to generate a universal vaccine against influenza A viruses that provides broadly cross-reactive protection through the induction of antibodies or T cells to conserved regions of the virus.

negative: COVID-19, SARS and MERS: are they closely related? Abstract Background The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. Aims To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. Sources The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. Content COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0–2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7–1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. Implications There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

negative: Biosafety and biosecurity Abstract With the profound changes in the international security situation, the progression of globalization, and the continuous advancement of biotechnology, the risks and challenges posed by major infectious diseases and bioterrorism to the international community are also increasing. Biosafety, therefore, presents new opportunities for international cooperation and global governance. The world has become more integrated and now shares a common destiny in terms of biosafety. In the face of the current risks and challenges, the international community must work together to avert threats, advance mutual interests, and safeguard global biosecurity. In the context of the current situation regarding biosafety and biosecurity, we conducted the present analysis, and present here some appropriate countermeasures.

negative: Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites In this work, we study the consequences of sequence variations of the "2009 H1N1" (swine or Mexican flu) influenza A virus strain neuraminidase for drug treatment and vaccination. We find that it is phylogenetically more closely related to European H1N1 swine flu and H5N1 avian flu rather than to the H1N1 counterparts in the Americas. Homology-based 3D structure modeling reveals that the novel mutations are preferentially located at the protein surface and do not interfere with the active site. The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu(®)), zanamivir (Relenza(®)) and peramivir; thus, the drugs should remain effective for treatment. However, the antigenic regions of the neuraminidase relevant for vaccine development, serological typing and passive antibody treatment can differ from those of previous strains and already vary among patients. This article was reviewed by Sandor Pongor and L. Aravind.

negative: Splitting one ventilator for multiple patients -- a technical assessment Due to the recent coronavirus outbreak, many efforts and innovative solutions have surfaced to deal with the possible shortage of ventilators upon catastrophic surges of patients. One solution involves splitting one ventilator to treat multiple patients and is in principle easy to implement, but there are obvious risks, and little is known on how the technique would work on patients with ARDS from Covid-19. Previous studies have shown that multiple test lungs of equal characteristics can be successfully ventilated from one machine, but that large variations in tidal volume delivery occurs when lungs with different compliance are connected. In contribution to the discussion of the feasibility of the technique, a technical assessment was done including experiments expanding on the previous studies using two types of test lungs, different ventilator settings and test lung characteristics. Using two test lungs connected to a ventilator, the tidal volumes and pressures into both lungs were measured for different combinations of lung compliance, airway resistances, modes of ventilation, inspiratory and end-expiratory pressure levels. We found discrepancies in delivered tidal volumes for paired test lungs proportional with compliance differences, little influence from differences in airway resistances, and that changes in compliance of only one test lung would also change the tidal volume delivered to the other test lung when in volume controlled mode. For one of the test lung types, we also found that higher PEEP settings could strongly influence the tidal volume balance between the test lungs. From this study and from a technical point of view, we were not able to identify reliable settings, adjustments or any simple measures to overcome the hazards of this simple technique, and a more advanced solution is indicated for mitigating risks.

negative: Is death from Covid-19 a multistep process? Covid-19 death has a different relationship with age than is the case for other severe respiratory pathogens. The Covid-19 death rate increases exponentially with age, and the main risk factors are age itself, as well as having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. Furthermore, the almost complete lack of deaths in children suggests that infection alone is not sufficient to cause death; rather, one must have gone through a number of changes, either as a result of undefined aspects of aging, or as a result of chronic disease. These characteristics of Covid-19 death are consistent with the multistep model of disease, a model which has primarily been used for cancer, and more recently for amyotrophic lateral sclerosis (ALS). We applied the multi-step model to data on Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of ln (CFR) against ln (age) was approximately linear with a slope of about 5. As a comparison, we also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log-log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multistep model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Identification of these steps would be potentially important for prevention and therapy for SARS-COV-2 infection.

negative: Antiviral Drugs for Influenza and Other Respiratory Virus Infections

negative: Co-infections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents? Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.

negative: Psychosocial determinants of influenza vaccination intention: A cross-sectional study on inpatient nurses in Singapore Nurses have the closest interaction with inpatients and could transmit influenza to patients. From a self-administered questionnaire survey among inpatient nurses at a tertiary hospital, we observed that the strongest factors associated with intention for future vaccination were perceived benefits of and motivations for vaccination (adjusted odds ratio [aOR], 3.30; 95% confidence interval [CI], 2.55-4.27), and perceived nonsusceptibility to influenza and preference for vaccination alternatives (aOR, 0.26; 95% CI, 0.20-0.34). These factors need to be addressed to increase vaccination uptake and prevent nosocomial transmission.

negative: Systems approaches to influenza-virus host interactions and the pathogenesis of highly virulent and pandemic viruses Influenza virus research has recently undergone a shift from a virus-centric perspective to one that embraces the full spectrum of virus-host interactions and cellular signaling events that determine disease outcome. This change has been brought about by the increasing use and expanding scope of high-throughput molecular profiling and computational biology, which together fuel discovery in systems biology. In this review, we show how these approaches have revealed an uncontrolled inflammatory response as a contributor to the extreme virulence of the 1918 pandemic and avian H5N1 viruses, and how this response differs from that induced by the 2009 H1N1 viruses responsible for the most recent influenza pandemic. We also discuss how new animal models, such as the Collaborative Cross mouse systems genetics platform, are key to the necessary systematic investigation of the impact of host genetics on infection outcome, how genome-wide RNAi screens have identified hundreds of cellular factors involved in viral replication, and how systems biology approaches are making possible the rational design of new drugs and vaccines against an ever-evolving respiratory virus.

negative: Coronavirus Disease 2019 (COVID-19) and pregnancy: what obstetricians need to know Coronavirus disease 2019 is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about coronavirus disease 2019 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (ie, severe acute respiratory syndrome and the Middle East respiratory syndrome) might provide insights into coronavirus disease 2019’s effects during pregnancy. Coronaviruses cause illness ranging in severity from the common cold to severe respiratory illness and death. Currently the primary epidemiologic risk factors for coronavirus disease 2019 include travel from mainland China (especially Hubei Province) or close contact with infected individuals within 14 days of symptom onset. Data suggest an incubation period of ∼5 days (range, 2–14 days). Average age of hospitalized patients has been 49–56 years, with a third to half with an underlying illness. Children have been rarely reported. Men were more frequent among hospitalized cases (54–73%). Frequent manifestations include fever, cough, myalgia, headache, and diarrhea. Abnormal testing includes abnormalities on chest radiographic imaging, lymphopenia, leukopenia, and thrombocytopenia. Initial reports suggest that acute respiratory distress syndrome develops in 17–29% of hospitalized patients. Overall case fatality rate appears to be ∼1%; however, early data may overestimate this rate. In 2 reports describing 18 pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnant adults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of in utero transmission was seen. Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratory syndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in 4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanical ventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended in spontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks’ gestation delivered preterm. For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmission was seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently no coronavirus-specific treatments have been approved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk for pregnancy complications, management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue to follow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html).

negative: A Bat-Derived Putative Cross-Family Recombinant Coronavirus with a Reovirus Gene The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 has generated enormous interest in the biodiversity, genomics and cross-species transmission potential of coronaviruses, especially those from bats, the second most speciose order of mammals. Herein, we identified a novel coronavirus, provisionally designated Rousettus bat coronavirus GCCDC1 (Ro-BatCoV GCCDC1), in the rectal swab samples of Rousettus leschenaulti bats by using pan-coronavirus RT-PCR and next-generation sequencing. Although the virus is similar to Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9) in genome characteristics, it is sufficiently distinct to be classified as a new species according to the criteria defined by the International Committee of Taxonomy of Viruses (ICTV). More striking was that Ro-BatCoV GCCDC1 contained a unique gene integrated into the 3’-end of the genome that has no homologs in any known coronavirus, but which sequence and phylogeny analyses indicated most likely originated from the p10 gene of a bat orthoreovirus. Subgenomic mRNA and cellular-level observations demonstrated that the p10 gene is functional and induces the formation of cell syncytia. Therefore, here we report a putative heterologous inter-family recombination event between a single-stranded, positive-sense RNA virus and a double-stranded segmented RNA virus, providing insights into the fundamental mechanisms of viral evolution.

negative: Molecular influenza surveillance at a tertiary university hospital during four consecutive seasons (2012–2016) in Catalonia, Spain Abstract Background Influenza viruses (FLUV) are continuously evolving, which explain the occurrence of seasonal influenza epidemics and the need to review the vaccine strain composition annually. The aim is to describe the genetic diversity and clinical outcomes of FLUV detected at a tertiary university hospital in Barcelona (Spain) during the 2012–2016 seasons. Methods The detection of FLUV from patients attended at the Emergency Department or admitted to the hospital was performed by either immunofluorescence or PCR-based assays. A specific real-time one-step multiplex RT-PCR was performed for influenza A (FLUAV) subtyping. The complete coding haemagglutinin domain 1 (HA1) and neuraminidase (NA) (2015–2016) protein sequences from a representative sampling were molecular characterised. Results A total 1774 (66.1%) FLUAV and 910 (33.9%) influenza B (FLUBV) cases were laboratory-confirmed. The hospitalisation rate was different between seasons, being the highest (81.4%) during the 2014–2015 season. FLUV were genetically close to vaccine strains except to the 2014–2015, in which most characterised A(H3N2) viruses belonged to a genetic group different from the vaccine strain. During the 2015–2016 season, B/Victoria-like viruses were the most predominant, but this component was not included in the trivalent vaccine used. Mutations D222G or D222N in HA1-domain were found in 3 A(H1N1)pdm09 strains from ICU-admitted cases. Three A(H1N1)pdm09 strains carried the NA H275Y (2) and S247N (1) mutations, respectively related to resistance or decreased susceptibility to oseltamivir. Conclusions The circulation of drifted A(H3N2) strains during the 2014–2015 season was related to the high hospitalisation rate due to the mismatch with the vaccine strains. The predominance of a FLUBV lineage not included in the trivalent influenza vaccine during the 2015–2016 season highlights the need to use a tetravalent influenza vaccine. Virological surveillance of viral variants carrying protein changes that alter tropism and susceptibility to antivirals features should be strengthened in hospital settings.

negative: Major Infection Events Over 5 Years: How Is Media Coverage Influencing Online Information Needs of Health Care Professionals and the Public? BACKGROUND: The last decade witnessed turbulent events in public health. Emerging infections, increase of antimicrobial resistance, deliberately released threats and ongoing battles with common illnesses were amplified by the spread of disease through increased international travel. The Internet has dramatically changed the availability of information about outbreaks; however, little research has been done in comparing the online behavior of public and professionals around the same events and the effect of media coverage of outbreaks on information needs. OBJECTIVE: To investigate professional and public online information needs around major infection outbreaks and correlate these with media coverage. Questions include (1) How do health care professionals’ online needs for public health and infection control information differ from those of the public?, (2) Does dramatic media coverage of outbreaks contribute to the information needs among the public?, and (3) How do incidents of diseases and major policy events relate to the information needs of professionals? METHODS: We used three longitudinal time-based datasets from mid-2006 until end of 2010: (1) a unique record of professional online behavior on UK infection portals: National electronic Library of Infection and National Resource of Infection Control (NeLI/NRIC), (2) equivalent public online information needs (Google Trends), and (3) relevant media coverage (LexisNexis). Analysis of NeLI/NRIC logs identified the highest interest around six major infectious diseases: Clostridium difficile (C difficile)/Methicillin-resistant Staphylococcus aureus (MRSA), tuberculosis, meningitis, norovirus, and influenza. After pre-processing, the datasets were analyzed and triangulated with each other. RESULTS: Public information needs were more static, following the actual disease occurrence less than those of professionals, whose needs increase with public health events (eg, MRSA/C difficile) and the release of major national policies or important documents. Media coverage of events resulted in major public interest (eg, the 2007/2008 UK outbreak of C difficile/MRSA). An exception was norovirus, showing a seasonal pattern for both public and professionals, which matched the periodic disease occurrence. Meningitis was a clear example of a disease with heightened media coverage tending to focus on individual and celebrity cases. Influenza was a major concern during the 2009 H1N1 outbreak creating massive public interest in line with the spring and autumn peaks in cases; although in autumn 2009, there was no corresponding increase in media coverage. Online resources play an increasing role in fulfilling professionals’ and public information needs. CONCLUSIONS: Significant factors related to a surge of professional interest around a disease were typically key publications and major policy changes. Public interests seem more static and correlate with media influence but to a lesser extent than expected. The only exception was norovirus, exhibiting online public and professional interest correlating with seasonal occurrences of the disease. Public health agencies with responsibility for risk communication of public health events, in particular during outbreaks and emergencies, need to collaborate with media in order to ensure the coverage is high quality and evidence-based, while professionals’ information needs remain mainly fulfilled by online open access to key resources.

negative: A statistical forecast of LOW mortality (< 400,000 deaths) due to COVID-19, for the whole WORLD. OBJECTIVE: To forecast the death toll of COVID-19 in the whole world by fitting the time series of reported deaths with a parametric equation (integrated Gaussian equation) related to Farr s law. DATA: The time series of cumulative deaths due to COVID-19 produced by John Hopkins University and stored in a github repository. RESULTS: The projected total death toll will be 261680 (392520 to 183176) which represents the 0.003 % of world population. This number amounts to 0.054 deaths per 1000, while the mean in the world (all causes) is 7.7. The daily peak of deaths (7270 (+/-500)) happened the 15 (+/- 3) of April, meaning that we are in descending curve of the pandemic. The outbreak will end completely the 23th (+/-3) of June. However, already on 9th (+/- 3) of May, 2 sigma; (95.45%) of the deaths will have be occured. The projected death toll is much lower (5-10 times) than those forecasted by the Imperial College Group (ICG) even considering the best scenario of total suppression of virus transmission. Using actual mortality rates it is possible to back calculate which number of infected individuals would produce such mortality. The death toll arises from a number of infected individuals between 53 (worst case) and 3.3 million. The calculated number of infected individuals is significantly lower than that calculated by ICG (227.5 millions) with suppression.

negative: Biological Agents and Bioterrorism For this very stimulating course, I want to share with you some of my studies and even some of my scientific and phylosophical considerations on biological agents living in the environment and their relations with humans, in the very wide concepts of ecological relationships, parasitism, immunolgical defenses and infectious disease mechanisms. All these concepts must be studied and considered in the event of criminal use of biological agents (bioterrorism) aimed at harming human populations in time and in geographical space.

negative: Emerging viral diseases and infectious disease risks Summary. New pathogens and antimicrobial‐resistant forms of older pathogens continue to emerge, some with the potential for rapid, global spread and high morbidity and mortality. Pathogens can emerge either through introduction into a new population or when the interaction with the vector changes; emergence is also influenced by microbiological adaptation and change, global travel patterns, domestic and wild animal contact and other variants in human ecology and behaviour. Quick, decisive action to detect and control novel pathogens, and thereby contain outbreaks and prevent further transmission, is frequently hampered by incomplete or inadequate data about a new or re‐emerging pathogen. Three examples of pathogens that are current causes for human health concern are avian influenza, West Nile virus (WNV) and the severe acute respiratory syndrome (SARS) coronavirus. Pathogens directly or indirectly transmitted by aerosolized droplets, such as avian influenza and SARS, pose considerable containment challenges. Rapid screening tests for other newly described pathogens such as WNV require time for development and may be <100% reliable. The importance of vigilance in the detection and control of newly recognized infectious threats cannot be overstressed. The presence of infectious agents in the blood supply could again have a significant impact on the safe use of both blood and blood‐derived products in the care of patients with haemophilia, as did the human immunodeficiency virus in the 1980s. Emerging pathogens will continue to be a reality requiring the collaborative efforts of public health and individual healthcare providers worldwide to contain outbreaks and prevent transmission.

negative: A Model for Characterizing Annual Flu Cases Influenza outbreaks occur seasonally and peak during winter season in temperate zones of the Northern and Southern hemisphere. The occurrence and recurrence of flu epidemics has been alluded to variability in mechanisms such temperature, climate, host contact and traveling patterns [4]. This work promotes a Gaussian–type regression model to study flu outbreak trends and predict new cases based on influenza–like–illness data for France (1985–2005). We show that the proposed models are appropriate descriptors of these outbreaks and can improve the surveillance of diseases such as flu. Our results show that limited data reduces our ability to predict unobserved cases. Based on laboratory surveillance data, we prototype each season according to the dominating virus (H3N2, H1N1, B) and show that high intensity outbreaks are correlated with early peak times. These findings are in accordance with the dynamics observed for influenza outbreaks in the US.

negative: Die Bedeutung der aviären Influenza für das Gesundheitssystem Avian influenza is a viral transmitted disease that mainly occurs in birds. First described in 1878 in Italy the disease can be found worldwide. The causing agent belongs to the family of orthomyxoviridae. Since its enormous spread among poultry in 2003, the influenza virus H5N1 is heralded as a possible agent of a new pandemic. H5N1 is pathogen to humans with a mortality rate of over 60%. The main reason that this virus has not caused a pandemic yet is its lack to propagate freely between humans. The current review explores the impact of avian influenza on the health system.

negative: The use of pseudotypes to study viruses, virus sero-epidemiology and vaccination Abstract The globalization of the world's economies, accompanied by increasing international travel, changing climates, altered human behaviour and demographics is leading to the emergence of different viral diseases, many of which are highly pathogenic and hence are considered of great public and animal health importance. To undertake basic research and therapeutic development, many of these viruses require handling by highly trained staff in BSL-3/4 facilities not readily available to the majority of the global R&D community. In order to circumvent the enhanced biosafety requirement, the development of non-pathogenic, replication-defective pseudotyped viruses is an effective and established solution to permit the study of many aspects of virus biology in a low containment biosafety level (BSL)-1/2 laboratory. Under the spectre of the unfolding Ebola crisis, this timely conference (the second to be organised by the Viral Pseudotype Unit, www.viralpseudotypeunit.info*) discusses the recent advances in pseudotype technology and how it is revolutionizing the study of important human and animal pathogens (human and avian influenza viruses, rabies/lyssaviruses, HIV, Marburg and Ebola viruses). Key topics addressed in this conference include the exploitation of pseudotypes for serology and serosurveillance, immunogenicity testing of current and next-generation vaccines and new pseudotype assay formats (multiplexing, kit development). *The first pseudotype-focused Euroscicon conference organised by the Viral Pseudotype Unit was recently reviewed [1].