cord-000131-ugbwvy6j	2009	Here, we report the results from an online survey that gathered data (n = 6,249) about risk perception of the outbreak during the first few days of widespread media coverage (April 29 -May 5, 2009) of the emergence of novel swine-origin Influenza A(H1N1). To evaluate the hypothesis that respondents'' affective state (subjective anxiety, fatalism about infection) predicts protective measures, we include in the model demographic (age, gender), epidemiological (household size, number of contacts, survey day), and media (source of information on the outbreak) conditioning variables. While our sampling design is subject to many of the usual criticisms of internet-based surveys and is not necessarily representative of the general population, the unparalleled immediacy, longitudinal nature, and the large number of respondents it contains make our data set unique and scientifically important for the study of the spread of information and distribution of risk perception and behavioral change during the most uncertain time (i.e. the initial phase) of an epidemic of a virus novel to the human population.
cord-000161-hxjxczyr	2009	Primary influenza pneumonia has a high mortality rate during pandemics, not only in immunocompromised individuals and patients with underlying comorbid conditions, but also in young healthy adults. Pneumonia and the acute respiratory distress syndrome (ARDS) account for the majority of severe morbidity and mortality that accompany pandemic influenza infection [14] . A recent analysis of lung specimens from 77 fatal cases of pandemic H1N1v 2009 infection found a prevalence of concurrent bacterial pneumonia in 29% of these patients [31] . A recent World Health Organization treatment guideline for pharmacological management of 2009 pandemic H1N1v influenza A recommends the consideration of higher doses of oseltamivir (150 mg twice a day) and longer duration of treatment for patients with severe influenza pneumonia or clinical deterioration [44] . The rapid progression from initial typical influenza symptoms to extensive pulmonary involvement, with acute lung injury, can occur both in patients with underlying respiratory or cardiac morbidities and in young healthy adults, especially if obese or pregnant.
cord-000244-wrru98zg	2010	title: A cross-sectional survey to evaluate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination among European travellers to resource-limited destinations 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. 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. Questions included demographic data (gender, age, nationality, education, profession), travel-related characteristics (destination country, duration of stay, influenza risk perception, previous travel health advice, travel purpose, travel costs) and general attitudes and practices towards influenza vaccination (vaccination coverage, reasons to be vaccinated, reasons to refuse vaccination, motivations to consider vaccination with options for multiple answers except for the vaccination coverage). Risk perception and vaccination coverage regarding seasonal and pandemic influenza was very poor among European travellers to resource-limited destinations 
cord-000262-4owsb0bg	2010	In settings like Hong Kong, with the infrastructure and resources to implement such measures and N Decisions regarding pandemic response during the exigencies of a public health emergency must be judged according to the best evidence available at the time. Reduce and delay community spread somewhat at the earliest stage to allow better preparation for mitigation response [15] Completely prevent entry of infected individuals due to suboptimal sensitivity and asymptomatic (including infected and within incubation period) or subclinical presentation [16] Many countries did not attempt these measures because of logistics, stage of pandemic [22] or other cost-benefit considerations [16] China Hong Kong SAR Japan Personal protective measures (e.g., face masks, hand hygiene, cough etiquette, early self-isolation when ill) Reduce risk of infection to self and close contacts (if self is ill and infected) [27, 28] Have not been evaluated whether they can provide significant populationlevel protection
cord-000390-qav5okgk	2011	Therefore, as our primary strategy for confounder adjustment, we identified a group of covariates that would move the odds ratios (ORs) of association between maternal influenza immunization and birth outcomes during the pre-influenza period to 1.0 (i.e., no effect), hence arriving at a set of covariates that could effectively control for confounding due to the differences between the vaccinated and the unvaccinated women in analyses of all influenza activity periods. The most significant type of confounding in influenza studies is due to a higher likelihood of individuals with high functional capacity (i.e., healthier The primary adjusted models were based on the approach of identifying covariates that produce adjusted ORs of 1 during the pre-influenza period and included the following covariates: gestational age for first antenatal visit, maternal diabetes (gestational and/or non-gestational), multivitamin use in pregnancy, history of alcohol use during pregnancy, education less than 12th grade, and mother married.
cord-000724-lzhobnch	2011	The questionnaire collected the following data : (1) knowledge about seasonal influenza and vaccination (22 items requiring true, false or unsure responses) included five dimensions to assess general information, severity of influenza, influenza vaccination, high-risk groups and vaccination-recommended groups; (2) risk perception (12 items with a 4-point Likert scale) towards influenza and pandemic with three dimensions (i.e. personal vulnerability to illness, negative consequences of contracting influenza and severity of influenza) ; (3) health locus of control including internal, chance and powerful others dimensions assessed by the Multidimensional Health Locus of Control (MHLC) scales [28] (18 items) ; (4) vaccination behaviours (nine items) including vaccination status (whether respondents had been vaccinated in the previous season), vaccination intent (whether respondents intended to be vaccinated next season) and vaccination history (how many times respondents had been vaccinated in the last 5 years) ; (5) reasons for accepting or refusing vaccination using two open questions; and (6) demographic characteristics (10 items) including gender, age group, highest educational qualification, place of work, clinical speciality, year of qualification as a nurse and whether or not respondents had direct patient contact.
cord-000757-bz66g9a0	2012	Therefore, the purpose of this study was to demonstrate the feasibility of using a pipeline, composed of a detection rule and a natural language processor, for the real time encoding of death certificates using the identification of pneumonia and influenza cases as an example and demonstrating that its accuracy is comparable to existing methods. Other research groups [18, 19] have demonstrated the feasibility of using mortality data for real time surveillance but all used "free text" search for the string "pneumonia", "flu" or "influenza." As noted earlier, although this method can provide the semi quantitative measurements for disease surveillance purposes, keyword searches can also result in an array of problems that result from complexities of human language such as causal relationships and synonyms [20] . Although, the focus of this study was to use NLP techniques to process death certificates, the description of this system reported in the literature did not show how well coded data from an NLP tool along with predefined rules can detect countable cases for a specific disease or condition.
cord-000759-36dhfptw	2011	The existing models on pandemic influenza (PI) containment and mitigation aims to address various complex aspects of the pandemic evolution process including: (i) the mechanism of disease progression, from the initial contact and infection transmission to the asymptomatic phase, manifestation of symptoms, and the final health outcome [10] [11] [12] , (ii) the population dynamics, including individual susceptibility [13, 14] and transmissibility [10, [15] [16] [17] , and behavioral factors affecting infection generation and effectiveness of interventions [18] [19] [20] , (iii) the impact of pharmaceutical and nonpharmaceutical measures, including vaccination [21] [22] [23] , antiviral therapy [24] [25] [26] , social distancing [27] [28] [29] [30] [31] and travel restrictions, and the use of low-cost measures, such as face masks and hand washing [26, [32] [33] [34] . The single-region model subsumes the following components (see Figure 3 ): (i) population dynamics (mixing groups and schedules), (ii) contact and infection process, (iii) disease natural history, and (iv) mitigation strategies, including social distancing, vaccination, and antiviral application.
cord-000760-4yfohp9w	2012	Using peptide nanoparticle technology, we have designed two novel vaccine constructs representing M2e in monomeric (Mono-M2e) and tetrameric (Tetra-M2e) forms. A multiple antigenic peptide construct containing M2e (M2e-MAP) induced strong M2especific antibody titers in the serum of mice and resulted in significant protection against influenza virus challenge [13] . Chickens after each inoculation developed high levels of antibody against the injected construct and anamnestic response clearly was seen when the plates were coated with Mono-M2e and Tetra-M2e nanoparticles and M2e-GCN4 (tetrameric M2e), respectively (Table 1, Figures 7 and 8) . In the present study, protection efficiency of two different nanoparticle constructs harboring M2e was studied as possible vaccine candidates for low-pathogenicity avian influenza infection. Vaccination of chickens with recombinant Salmonella expressing M2e and CD154 epitopes increases protection and decreases viral shedding after low pathogenic avian influenza challenge
cord-000891-5r2in1gw	2012	Suspected and unsuspected cases were compared, and significant differences were found for age (53 versus 69 median years), severe respiratory failure (68.8% versus 20%), surgery (6.3% versus 60%), median days of ICU stay before diagnosis (1 versus 4), nosocomial infection (18.8% versus 66.7%), cough (93.8% versus 53.3%), localized infiltrate on chest radiograph (6.3% versus 40%), median days to antiviral treatment (2 versus 9), pneumonia (93.8% versus 53.3%), and acute respiratory distress syndrome (75% versus 26.7%). The variables recorded were age, sex, classification of the severity of underlying conditions according to the Charlson comorbidity index [6] , type of ICU, date and cause of ICU admission, APACHE II score [7] on admission to the ICU, date of onset of influenza symptoms, clinical manifestations and radiologic findings at diagnosis, date of TA sample collection, other samples tested for influenza and result, date of initiation of antiviral treatment, complications (septic shock, acute respiratory distress syndrome (ARDS)), outcome including mortality within 30 days after influenza diagnosis, and length of ICU and hospital stay.
cord-001154-7k59ogn0	2013	Evaluation of viral shedding, nasal and serum cytokines, clinical illness, and clinical outcomes were performed to compare severely immunocompromised individuals to nonimmunocompromised individuals with influenza infection. Immunocompromised patients with influenza had more severe disease/complications, longer viral shedding, and more antiviral resistance while demonstrating less clinical symptoms and signs on clinical assessment. Careful examination of symptoms and signs of infection, virological measurements, immunological studies, and clinical parameters were performed to investigate the natural pathogenesis of influenza in this group of severely immunocompromised hosts. The comparison of these individuals with nonimmunocompromised individuals during influenza infection demonstrated that the immunocompromised patients are at risk of more severe or complicated disease, which may be difficult to prevent with current vaccines and treat with current antivirals.
cord-001219-517gka4h	2014	We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. A hypothetical explanatory model was constructed to inform the analysis of the main research question; i.e. to what extent selfreported intentions to perform protective behaviors during influenza outbreaks can be explained by perceptions of threat and the ability to cope as outlined in the PMT, self-assessments of health status, trust in official information, and sociodemiographic factors.
cord-001289-qbct63p4	2014	Two recent publications reporting the creation of ferret-transmissible influenza A/H5N1 viruses [1, 2] are controversial examples of research that aims to produce, sequence and characterize ''''potential pandemic pathogens'''' (PPPs) [3] , novel infectious agents with known or likely efficient transmission among humans, with significant virulence, and for which there is limited population immunity. N Alternative approaches would not only be safer but would also be more effective at improving surveillance and vaccine design, the two purported benefits of gain-of-function experiments to create novel, mammalian-transmissible influenza strains. A further challenge to realizing public health benefits from PPP experimentation is that the predictability of phenotype from viral sequence is complex [38, 48, 49] , as demonstrated by a recent assessment [50] of the generality of mutations that conferred human receptor binding in engineered ferret-transmissible H5N1 strains.
cord-001521-l36f1gp7	2011	The IC 50 values determined in functional NI assays provide valuable information for detection of resistant viruses, but should not be used to draw direct correlations with drug concentrations needed to inhibit virus replication in the infected human host, as clinical data to support such inferences are inadequate. • Standardized reagents and protocols • Choice of detection technology • Simple instrumentation requirements • High sensitivity for use with low virus concentrations • Compatibility with batch-mode processing and largescale assay throughput • Broad specificity of influenza detection • Flexibility in assay format • Additional NA assay applications -cell-based viral assays, screening for new NIs, detection of NA from other organisms Functional neuraminidase inhibition assays enable detection of any resistance mutation and are extremely important in conjunction with sequence-based screening assays for global monitoring of virus isolates for NI resistance mutations, including known and new mutations. Such new assays need to include methods to measure local antibodies and virus-specific lymphocytes, especially in the case of live attenuated influenza vaccines, because of their potential to induce such broad-based immune responses.
cord-001634-mi5gcfcw	2015	In relation to pandemic influenza, public communications feature in preparedness and response planning which requires that members of the general public adopt measures during a public health emergency, including: hygiene (e.g., covering the mouth and nose when sneezing or coughing, washing hands, keeping surfaces clean, avoiding sharing personal items) and the avoidance of close contact with others [4] . This paper, therefore, uses inductive, qualitative research methods to develop new knowledge on how members of the general population respond to pandemic influenza, set against the backdrop of the assumed resistance on the part of the general public and related critiques, including, health risk fatigue, the risk communication dilemma and individualism. The research aimed to identify how members of the general public respond to pandemic influenza so that public health communications can be designed to engage with how its audiences respond to risk messages and how they enact hygiene, social isolation and related measures.
cord-001654-o2zfilcl	2015	The use of immunomodulatory agents such as statins to target host inflammatory responses in influenza virus infection has been suggested as an adjunct treatment, especially during pandemics, when antiviral quantities are limited or vaccine production can be delayed. We used population-based, influenza hospitalization surveillance data, propensity score-matched analysis, and Cox regression to determine whether there was an association between mortality (within 30 days of a positive influenza test) and statin treatment among hospitalized cohorts from 2 influenza seasons (October 1, 2007 to April 30, 2008 and September 1, 2009 to April 31, 2010). A study by Vandermeer et al [23] , using data from a populationbased influenza surveillance system, found a protective effect of statin use on mortality among patients hospitalized with laboratory-confirmed influenza during the 2007-2008 influenza season. We used Cox proportional hazards models with robust standard errors, stratified on matched pairs, to determine the effect of statin treatment on mortality within 30 days of a positive influenza test.
cord-001746-pbahviaz	2015	Although there is evidence that adult patients with underlying cardiac or pulmonary disease are more likely to develop influenza-associated pneumonia than those without underlying medical conditions [6, 7] , much of the data describing factors associated with influenzaassociated pneumonia among adults comes from case series conducted at single sites and during a limited number of seasons. The following data were collected on patients: demographics, results of laboratory tests for influenza, influenza vaccination status for the current season, underlying medical conditions, bacterial coinfections, CXR data, antiviral treatment, clinical outcomes, and discharge diagnoses. Patients with pneumonia were significantly more likely than patients without pneumonia to reside in a nursing home prior to hospital admission, to have received influenza vaccine, and to have the following underlying medical conditions: chronic lung disease, cardiovascular disease, and immunosuppression.
cord-001826-av2gxfxy	2014	In this study we established a 293T cell line that constitutively synthesizes a virus-based negative strand RNA, which expresses Gaussia luciferase upon influenza A virus infection. The dynamic signal range of the Gluc reporter assay was assessed by infecting 293T-Gluc cells with varying quantities of influenza A/WSN/33 virus (MOI of 0.0001, 0.001, 0.01, 0.1 and 1) and determining Gluc activity at various times post-infection (12, 24, 36 and 48 h post-infection). For evaluation assay of antivirals and high-throughput screening, 1 μL of each tested compound was added to cells and incubated for 2 h prior to infection, after which cells were infected with influenza A/WSN/33 virus at an MOI of 0.05. The above results suggest the potential to use the Gluc reporter assay to screen compounds against influenza A virus. In this work we reported a cell-based high-throughput assay to identify inhibitors for influenza virus.
cord-002136-mkl89qkt	2009	Objectives We aimed to develop an air interface EVOC using pig tracheas in the study of influenza infection demonstrating that tracheal explants can be effectively maintained in organ culture and support productive influenza infection. 1, 3 Influenza infection in humans and pigs is primarily restricted to the upper and lower respiratory tract with viral replication occurring in the epithelial cells present on the surface of the respiratory mucosa. Ex vivo organ cultures (EVOC) of tracheal explants with an air interface system have been successfully developed and used in the study of both human and animal respiratory pathogens. To determine if the swine tracheal explants supported productive viral replication, explants were infected with 2AE5 · 10 2 pfu of swine influenza virus and maintained in organ culture for 5 days. Cultures of equine respiratory epithelial cells and organ explants as tools for the study of equine influenza virus infection
cord-002137-j5sfiyz8	2010	Nevertheless, these findings highlight that more needs to be done to understand barriers to vaccination in this group, to inform the development of appropriate strategies to increase vaccination coverage in primary health care staff, with a special focus on PNs. Influenza is a serious respiratory virus which costs the Australian healthcare system $115 million annually. Whilst there have been numerous Australian studies on influenza vaccine uptake amongst hospital and institutional HCWs 6, [9] [10] [11] [12] [13] and some studies on attitudes of primary care clinicians to influenza vaccination for their patients 14, 15 , there has been limited published studies to date on influenza vaccination coverage, barriers and enablers amongst primary health care staff in Australia. More recently, a national survey from the Australian General Practice Network (AGPN) 23 assessed influenza vaccination coverage in GPs and PNs in the same years as our study (2007 ⁄ 2008) with similar response rates (34% versus 36%).
cord-002337-8v907g24	2016	
cord-002407-25cawzi0	2016	
cord-002408-bbtslrrt	2017	We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy. To investigate the possibility of LTZs in a large regional area, we analyze clinical data from a healthcare medical center in the city of Jerusalem, containing the clinical test results for Influenza virus and Respiratory Syncytial Virus (RSV) from patients presenting with ILI symptoms. Our analysis finds that while Influenza and RSV incidences tend to overlap and show more or less equal number of cases over the whole region, individual LTZs show a far more homogeneous disease content at most given times, with some being dominated by RSV while others by Influenza.
cord-002438-b8t4a57r	2017	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. In this study, we used four-year continuous surveillance data to compare the epidemic and virological characteristics of influenza virus between ILI cases and SARI cases in Zhejiang Province. Correlation analysis of weekly influenza virus type/subtype constitution among total positive numbers between influenza-like illness (ILI) and severe acute respiratory illness (SARI). Our findings further demonstrated that young children are vulnerable for both mild and severe respiratory infection, and the low influenza detection rate among 0-4 years age-group in both SARI and ILI patients foreshadow the need of expand the respiratory illness surveillance to more types of pathogens [12, 24] .
cord-002852-m4l2l2r1	2012	authors: Munyua, Peninah M.; Githinji, Jane W.; Waiboci, Lilian W.; Njagi, Leonard M.; Arunga, Geoffrey; Mwasi, Lydia; Murithi Mbabu, R.; Macharia, Joseph M.; Breiman, Robert F.; Kariuki Njenga, M.; Katz, Mark A. Background Surveillance for influenza viruses within live bird markets (LBMs) has been recognized as an effective tool for detecting circulating avian influenza viruses (AIVs). Efforts should be made to promote practices that could limit the maintenance and transmission of AIVs in LBMs. Influenza A viruses are zoonotic pathogens that infect a variety of domestic poultry such as chickens, turkeys, ducks, and geese. 2, 4, 5 Surveillance for influenza viruses within live bird markets (LBMs) has been recognized as an effective tool for detecting circulating influenza subtypes in the poultry population. 7, 8 Influenza viruses have also been detected in various environmental specimens collected in contaminated areas in LBMs including drinking water troughs, and surfaces in the delivery, holding and slaughter areas in markets.
cord-002919-6xjm7f29	2018	title: Clinical characteristics from co-infection with avian influenza A H7N9 and Mycoplasma pneumoniae: a case report Here, we reported the case of a woman co-infected by influenza A H7N9 and Mycoplasma pneumoniae, whose treatment process was a little bit longer and a little bit complicated as well. However, some symptoms exacerbated again 2 days later with ground-glass changes appearing in upper area of right lung and the titer of antibody to Mycoplasma pneumoniae rising from 1:80 to 1:640. CONCLUSION: In patients with confirmed influenza A H7N9 infection whose condition worsens again, especially with new infiltration or lung ground-glass infiltration, one should suspect infection by other pathogens such as Mycoplasma pneumoniae. In cases of confirmed influenza A H7N9, if the condition of the patient is not under initial treatment or if it even worsens with new ground-glass lung infiltrates, infection with another pathogen including MP must be suspected and sought.
cord-002939-6a3ga6v9	2018	To investigate the factors associated with death and describe the gestational outcomes in pregnant women with influenza A(H1N1)pdm09, we conducted a case-control study (deaths and recovered) in hospitalized pregnant women with laboratory-confirmed influenza A(H1N1)pdm09 with severe acute respiratory illness (SARI) in the state of São Paulo from June 9 to December 1, 2009. The objective of this study was to analyze factors associated with death in pregnant women with influenza A(H1N1) pdm09 and severe acute respiratory illness (SARI) and describe the gestational and neonatal outcomes. A case-control study was conducted that evaluated pregnant women living in São Paulo with confirmed infection of influenza A(H1N1)pdm09 and hospitalized with SARI, defined as: fever and cough and dyspnea or pneumonia or respiratory failure or tachypnea or radiological alterations consistent with pneumonia or oxygen therapy or mechanical ventilation.
cord-002972-ge7qt256	2018	OBJECTIVE: The Plan of Information on Acute Respiratory Infections in Catalonia (PIDIRAC) included the surveillance of severe hospitalized cases of laboratory-confirmed influenza (SHCLCI) in 2009. Surveillance of SHCLCI provides an estimate of the severity of seasonal influenza epidemics and the identification and characterization of at-risk groups in order to facilitate preventive measures such as vaccination and early antiviral treatment. Given the situation generated by the 2009 pandemic caused by the new influenza A (H1N1) pdm09 virus, the PIDIRAC sentinel network included surveillance of severe hospitalized cases of laboratory-confirmed influenza (SHCLCI) to assess severity. The aims of SHCLCI surveillance are to provide an estimate of the severity of seasonal influenza epidemics to identify and characterize the risk groups that may present serious complications as a result of infection by circulating influenza viruses or their association with some underlying diseases and to identify the virological characteristics of viruses associated with these severe cases, such as genetic changes and/or antigenic changes that lead to increased virulence.
cord-003099-a0acr28o	2018	
cord-003122-a3f4l6iu	2018	The segmentation of the influenza genome makes these additional trafficking requirements especially challenging, as each viral RNA (vRNA) gene segment must navigate the network of cellular membrane barriers during the processes of entry and assembly. To accomplish this goal, influenza A viruses (IAVs) utilize a combination of viral and cellular mechanisms to coordinate the transport of their proteins and the eight vRNA gene segments in and out of the cell. Influenza A viruses (IAVs) and type B viruses (IBVs) contain 8, negative-sense, single-stranded viral RNA (vRNA) gene segments ( Figure 1A ) (3, 4) , which encode transcripts for 10 essential viral proteins, as well as several strain-dependent accessory proteins ( Figure 1B) . In contrast to the early steps in IAV entry, vRNP trafficking to the nucleus following the fusion event is highly dependent on the host cell machinery and transport pathways [reviewed in Ref.
cord-003232-nquw7qga	2018	
cord-003302-vxk7uqlc	2018	
cord-003466-599x0euj	2019	
cord-003523-byxuruk1	2019	
cord-003567-h8uq5z8b	2019	
cord-003571-upogtny6	2018	In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. age patterns; history of epidemiology; influenza; mortality; pandemic; prior immunity One hundred years after the fact, the 1918 influenza pandemic remains one of the most important epidemics of the modern medical era; it was significant for its impact on both human health and the development of epidemiology and other medical sciences.
cord-003598-m2fsrwvw	2019	
cord-003701-i70ztypg	2019	
cord-003870-hr99dwi7	2019	Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses. Factors predicted to confer more specific susceptibility to influenza are placed higher in the diagram independently associated with severe disease from either seasonal or pandemic IAV [24] . Susceptibility to severe H1N1 infection was analysed in a recent genome-wide study (integrated with data on genetic variants associated with altered gene expression) which implicated an intronic SNP of GLDC, rs1755609-G [80] . Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age).
cord-003898-y6zpvw84	2019	
cord-004060-nxw5k9y1	2019	
cord-004280-c470nlie	2020	
cord-004348-4jdn4kw6	2020	
cord-004638-ijncfuxi	2020	In this study, we use the data from a chronic disease management information system in Shanghai to estimate vaccination coverage and characterize predictors of seasonal influenza and 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination among people with chronic disease in Shanghai. The elderly and patients with chronic disease including diabetes, COPD and heart disease are recommended to be priority groups for pneumococcal and influenza vaccination by the World Health Organization (WHO) [15, 16] and by the US Centers for Disease Control and Prevention (CDC) [17] . In this study, we use the data from a chronic disease management information system in Shanghai to estimate vaccination coverage and characterize predictors of influenza and pneumococcal vaccination among people with chronic disease in Shanghai. In a large sample of individuals with chronic diseases residing in Shanghai, China, we found low pneumococcal vaccination coverage over a 4-year study period and even lower influenza vaccine coverage.
cord-005081-kxrzv16n	2010	
cord-005314-p7hzoz5d	2010	
cord-006089-08g206kf	2006	
cord-006172-ndmf5ekp	2010	
cord-006252-cbelsymu	2012	
cord-006345-03kqeed3	2010	
cord-006362-7d5wzb7p	2016	
cord-006517-845w9r6l	2017	The aim of the present study was to assess the frequency and clinical impact of hematological abnormalities in the range of those accepted by the Histyocite Society for the suspicion of HPS [19] in patients who were admitted to the hospital with a confirmed influenza virus infection. In Beutel''s study of 25 critically ill patients with influenza A (H1N1) pdm09 virus associated hemophagocytic syndrome, the absence of steroid therapy in the early phase of the infection might have contributed to the high incidence of HPS (9 out of 25 patients) and the rather poor outcomes [18] . Significant hematological abnormalities are frequently seen in patients with influenza virus infection who required hospital admission and are associated with a poor outcome.
cord-007294-qeb2r08t	1971	
cord-007575-5ekgabx5	2016	Important trends and developments in the field include (1) the emergence of a Chlamydia psittaci strain (TWAR) that is passaged from human to human, causes a mycoplasma-like illness, and that is relatively resistant to erythromycin, (2) the recognition of respiratory syncytial virus as a pathogen in nursing home outbreaks and in immunosuppressed adults, (3) the continuing high lethality of fully developed influenza pneumonia, (4) the efficacy of acyclovir and adenine arabinoside in limiting the complications of varicella-zoster virus infections, and (5) the increasing frequency of pneumonia caused by cytomegalovirus and the severity of this disorder in highly immunosuppressed patients. Important trends and developments in the field include (1) the emergence of a Chlamydia psittaci strain (TWAR) that is passaged from human to human, causes a mycoplasma-like illness, and that is relatively resistant to erythromycin, (2) the recognition of respiratory syncytial virus as a pathogen in nursing home outbreaks and in immunosuppressed adults, (3) the continuing high lethality of fully developed influenza pneumonia, (4) the efficacy of acyclovir and adenine arabinoside in limiting the complications of varicella-zoster virus infections, and (5) the increasing frequency of pneumonia caused by cytomegalovirus and the severity of this disorder in highly immunosuppressed patients.
cord-007583-owxcokge	2014	Fortunately, dental health care workers follow a set of standard infection control precautions. dUrgent dental treatment can be performed without the use of an airborne infection isolation room because transmission of 2009 H1N1 influenza is thought not to occur across longer distances through the air, such as from one patient room to another. 1 Basic principles of this etiquette include the following: dEducate staff members, patients and visitors regarding the importance of containing respiratory secretions to help prevent the transmission of influenza and other respiratory In theory, any measure that limits the dispersal of respiratory droplets should reduce the opportunity for transmission of infection. Despite the economic and ethical pressure to keep working despite illness, dental personnel should take action to prevent the transmission of 2009 H1N1 influenza in their practices. Infection control in dental settings: prevention of 2009 H1N1 influenza transmission in dental health care settings
cord-007681-vhghhvnu	2009	Factors contributing to the decision to reassess the recommendations included a shift in national pandemic planning assumptions to a more severe pandemic scenario extrapolated from the 1918 pandemic (Table 1 ); recognition that the HHS guidance did not include groups that could be considered for prioritization such as border protection personnel or the military; a broader understanding of the risk to essential services stimulated by the NIAC report; and a series of public engagement meetings convened by the CDC, where participants identified protecting essential community services as the most important goal for pandemic vaccination rather than protecting those who are at highest risk (Public Engagement Pilot Project on Pandemic Influenza 2005). Reflecting the similar value placed by the public on protecting persons who provide pandemic healthcare, who maintain essential community services or are at high occupational risk, and protecting children, each of the highest vaccination tiers for a severe pandemic includes groups from each category (Table 4) .
cord-007733-zh8e76w7	2009	
cord-007784-fq2urilg	2011	
cord-007876-s5y6gyut	2017	
cord-008584-4eylgtbc	2020	
cord-008695-y7il3hyb	2007	
cord-008716-38sqkh9m	2001	
cord-008837-74rfnt1x	2005	
cord-009137-wj5vhvxx	1977	
cord-010416-u0yo0lk6	2020	
cord-010786-w3kjc6so	2019	
cord-010959-sigw7yxk	2020	
cord-011251-rjyipcfv	2019	
cord-011438-imbpgsub	2020	Upon IAV infection, host innate immune system is triggered and activated to restrict virus replication and clear pathogens. In the current review, we present a general description on recent work regarding different host cells and molecules facilitating antiviral defenses against IAV infection and how IAVs antagonize host immune responses. Host innate immunity, including phagocytic cells, interferons (IFNs), proinflammatory cytokines, etc., applies multiple mechanisms in defending IAV infection [105] . Influenza A virus nucleoprotein induces apoptosis in human airway epithelial cells: Implications of a novel interaction between nucleoprotein and host protein Clusterin Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1β production The human interferon-induced MxA protein inhibits early stages of influenza A virus infection by retaining the incoming viral genome in the cytoplasm Cell death regulation during influenza A virus infection by matrix (M1) protein: A model of viral control over the cellular survival pathway
cord-011712-fyrbe8tw	2020	METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment. We undertook a one-stage individual participant data (IPD) [16] meta-analysis to explore the association between NAI treatment of patients hospitalized with 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) infection and the LoS during the 2009-2010 influenza pandemic. In Hong Kong, a study of 356 adult patients hospitalized with laboratory-confirmed seasonal influenza showed that early oseltamivir treatment was associated with a reduced LoS in both unadjusted and multivariable analyses [9] , compared with no or later treatment, with the median LoS decreasing from 6 to 4 days; this accords with our primary analysis.
cord-011722-82qzf8ht	2014	
cord-011754-lumzp1ca	2013	Numerous observational studies have estimated that influenza vaccine reduces the risk of all-cause mortality among seniors during the winter months by 40% or more and have concluded that influenza vaccine is highly effective (4, (6) (7) (8) . Strong evidence for confounding comes from studies that have estimated the association between influenza vaccination and risk of death during time periods before, during, and after the seasonal circulation of influenza. If the same trends in apparent associations between vaccination and mortality were observed during a year when there could be no true vaccine effect, the claim that confounding differs between time periods would be refuted. We do not believe there was a true difference between associations in these two years, as the hazard ratio estimates were further from the null during the 2007/2008 control time periods ( preinfluenza and summer, when any apparent association is the result of uncontrolled confounding) as well as during influenza season.
cord-011757-11r3dnse	2018	
cord-011917-6u0t4hy8	2020	
cord-013022-c8a8ocge	2020	
cord-013073-siy7dvlo	2020	
cord-015646-tt2p9uue	2018	
cord-015764-ly68q5z0	2016	
cord-015830-ha8oj1b3	2009	Om verspreiding van het virus in deze fase zoveel mogelijk te beperken dient men profylactisch antivirale medicatie te geven aan contacten van patiënten met aviaire influenza (postexpositieprofylaxe). Postexpositieprofylaxe: profylactische behandeling met antivirale middelen van personen die -waarschijnlijk -in contact zijn geweest met een virologisch bevestigd geval van influenza maar bij wie zich nog geen ziekteverschijnselen hebben geopenbaard. Postexpositieprofylaxe Postexpositieprofylaxe met antivirale middelen (dat wil zeggen profylaxe van mensen die in contact zijn geweest met een patiënt met aviaire influenza, zoals gezinsleden) is alleen geïndiceerd tijdens een dreigende pandemie (WHOfasen 3 t/m 5). Een recent onderzoek heeft laten zien dat behandeling van influenza met oseltamivir ook bij risicogroepen kan leiden tot minder gebruik van antibiotica voor influenzagerelateerde lageluchtweginfecties. Men neemt aan dat patiënten die een neuraminidaseremmer krijgen bij de eerste symptomen van influenza -en niet profylactisch -, een immunologische bescherming tegen het virus opbouwen en daardoor bij een tweede besmetting niet (of veel minder) ziek worden.
cord-016475-7ldxvbpz	2006	After influenza virus infection antibodies directed against all major viral proteins can be detected in humans and the level of serum antibodies correlate with resistance to disease (Couch, 2003; Couch and Kasel, 1983; Coulter et al., 2003; Nichol et al., 1998; Potter and Oxford, 1979) . Nevertheless, IKK and NFκB might not only have anti-viral functions as two recent studies demonstrate that influenza viruses replicate much better in cells where NFκB is pre-activated (Nimmerjahn et al., 2004; Wurzer et al., 2004) . Apoptosis is mainly regarded to be a host cell defense against virus viruses (reviewed in: Julkunen et al., 2000; Ludwig et al., 2003; infections since many viruses express anti-apoptotic proteins to prevent this cellular response. Influenza virus-induced NF-kappaB-dependent gene expression is mediated by overexpression of viral proteins and involves oxidative radicals and activation of IkappaB kinase
cord-016995-5izyl234	2008	
cord-017291-bhe34dky	2017	Children aged <5 years (especially those <2 years) and those with underlying illness such as cardiac, respiratory and severe neurologic disease have an increased risk of severe outcomes associated with influenza. Vaccine cannot be given to children aged <6 months but maternal influenza immunization during pregnancy is recommended and can confer protection to the young infant. The highest rates of influenza-associated hospitalizations and deaths are typically seen in individuals aged ≥65 years, <5 years and those with underlying medical conditions that confer an increased risk for severe influenza [9] . Therefore, in Table 2 .1 Children at high risk of severe influenza in whom influenza antiviral treatment is recommended by the Centers for Disease Control and Prevention (CDC) and American Academy of Pediatrics (AAP) current guidance [9, 39] 1.
cord-017354-cndb031c	2008	
cord-017733-xofwk88a	2018	
cord-017748-xy26tk0t	2009	This, coupled with the difficulty to predict which subtype of avian influenza virus will cause the next human pandemic means that an ideal vaccine would elicit an immune response that protects the host from infection with a broad range of influenza viruses from the same or different subtypes (14) . Therefore, if a virus with a new HA and/or NA glycoprotein emerges in the human population, cell-mediated immunity directed against the highly conserved internal proteins could have a role in protection at the time of a pandemic (14) . Although most influenza vaccines are designed to induce HA-specific antibody responses to protect the host from infection, the biology of avian influenza viruses presents several unique challenges compared with human influenza viruses. DNA vaccines encoding the HA and NA glycoproteins of avian influenza viruses or conserved internal virus proteins, such as matrix proteins and nucleoproteins, induced protective immunity in mice and chickens (90) (91) (92) (93) .
cord-017893-ck0m3h7u	2007	
cord-018089-m94q75xn	2010	
cord-018213-w6sh9f3h	2018	
cord-018811-zhwr3h07	2010	The international investment into public health measures for a global human outbreak of avian H5N1 influenza together with a focus of swine influenza H1N1 is leading to enhanced production of conventional vaccine and to a new research searchlight on T-cell epitope vaccines, viral live-attenuated carriers of influenza proteins, and even more innovative substrates to cultivate virus, including plant cells. This was particularly well demonstrated by studies during the swine influenza campaign in the USA in 1976, when many observers reported results, which ultimately led to the recommended use in children of two doses of split-type rather than whole-virus vaccines. It has been known for many years that the serological response to inactivated vaccine depends on the previous experience of the recipient to infection by viruses of the same subtype of influenza A virus as that present in the vaccine. Comparison of inactivated vaccine A/HongKong/68 (H3N2) given intranasally or subcutaneously showed that following challenge with live virus only those who had developed a serum antibody response after vaccine by either route resisted infection.
cord-019010-9xgwjvsv	2010	
cord-019057-3j2fl358	2018	
cord-020466-hdcke0d4	2004	1 In the late 1990s, after several decades of fairly stable human influenza viruses, highly pathogenic avian influenza infected humans in Southeast Asia for the first time. In the setting of the severe acute respiratory syndrome (SARS) epidemic and emerging human infections with these highly pathogenic avian influenza strains, the prospect of a pandemic looms large for public health authorities and should prompt preparative measures from emergency care providers. 4, 5 Alternatively, a person infected with a conventional human influenza virus could be coinfected with a highly pathogenic avian influenza strain. 4 Formerly known as ''''fowl plague,'''' highly pathogenic avian influenza is now identified as strains H5 and H7, which cause severe disease in terrestrial birds. 17 Full respiratory isolation precautions, similar to those for SARS, are recommended in all cases of suspected human infection with highly pathogenic avian influenza viruses.
cord-020756-d9f5fd7x	2007	
cord-020789-slsfhrkx	2017	
cord-023666-r9zaf6un	2018	
cord-023859-3v9cmok0	2011	
cord-026641-eemp6b5j	2020	
cord-026982-1igz6i8u	2020	
cord-027752-xcpv9k22	2011	
cord-028564-sltofaox	2020	
cord-030279-pv770doe	2016	From ''dual-use life science research of concern'' through the rise of amateur biology to the advent of personalised medicine, the chapter exposes the limitations of the existing governance mechanisms in accommodating the multifaceted ethical, social, security, and legal concerns arising from cutting-edge scientific and technological developments. Indeed, rapid advances in the field have produced a knowledge base and set of tools and techniques that enable biological processes to be understood, manipulated and controlled to an extent never possible before 5 ; they have found various applications in numerous spheres of life, generating enormous benefits and offering bright prospects for human betterment; and they have come to be regarded as a key driver of economic development with potential to close the gap between resource-rich and resource-poor countries.
cord-030853-3yryw3r2	2020	title: Seasonal Influenza Vaccination and the Heightened Risk of Coronavirus and Other Pandemic Virus Infections: Fact or Fiction? During this ongoing severe acute respiratory illness coronavirus 2 (SARS-CoV-2) pandemic, few speculative reports on significant association of influenza vaccines with an increased risk of coronavirus infection appeared both in media and academic circles. That is, vaccinated individuals may be at increased risk for other respiratory viruses because they do not receive the non-specific immunity associated with natural infection [5, 6] . In a study of 115 children [6] , a significantly increased risk of virologically confirmed non-influenza respiratory virus infections was found to be associated with receipt of inactivated influenza vaccine. The contentious issue of higher risk of non-influenza respiratory viruses to influenza vaccinated individuals has gained traction during the ongoing SARS-CoV-2 pandemic, which is also a coronavirus infection. Increased risk of non-influenza respiratory virus infections associated with receipt of inactivated influenza vaccine
cord-048448-kfwbqp4p	2007	The recent emergence, host expansion, and spread of a highly pathogenic avian influenza (HPAI) H5N1 subtype in Asia have heightened concerns globally, both in regards to mortality from HPAI H5N1 infection in humans and the potential of a new pandemic. Influenza A viruses are characterized by their pathogenicity, with highly pathogenic avian influenza (HPAI) causing severe disease or death in domestic poultry [3] . Influenza A viruses infect a wide range of hosts, including many avian species, and various mammalian species, such as swine, ferrets, felids, mink, whales, horses, seals, dogs, civets, and humans [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] . Characterization of an avian influenza A virus isolated from a human -is an intermediate host necessary for the emergence of pandemic influenza viruses Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome
cord-103085-vf4qyvft	2020	Using Brownian dynamics simulations, we observe a twoto eight-fold decrease in the rate of ligand binding to the primary binding site of neuraminidase due to the presence of glycans. We have utilized BD to estimate the rates of binding of small molecules to the primary (i.e. active/catalytic) and secondary (i.e. hemadsorption) binding sites of influenza neuraminidase in glycosylated and unglycosylated states. The protein-ligand atom pairs were taken from crystal structures of ligands in the primary and secondary sites of neuraminidase for each monomer, and simulations were run for the full tetramer. Keeping in mind the primary and secondary binding sites are located just beneath the glycans (Figure 1) , the size and flexibility of the glycans here shows that they have the capability to "shield" the binding sites from ligand association. (A) The glycan structures from the MD simulations show a moderate association rate inhibition to the primary binding site irrespective of ligand chosen.
cord-103560-28o0bauv	2020	We developed an influenza transmission model that incorporates data on infectious viral load, social contact, and healthcare-seeking behavior, to evaluate the population-level impact of increasing antiviral treatment timeliness and coverage among high-risk patients in the US. We found that increasing the rate of early treatment among high-risk patients who received treatment more than 48 hours after symptoms onset, would substantially avert infections and influenza-induced hospitalizations. To evaluate the population-level impact of increased antiviral treatment coverage and timeliness of influenza-infected high-risk individuals during influenza seasons, we developed a data-driven influenza transmission model that incorporates data on infectious viral load, social contact, healthcare-seeking behavior, time to seek healthcare, and antiviral treatment. Nevertheless, for a 20% increase in influenza effective vaccination coverage among all age groups, our results suggest that the benefit of treatment remains substantial ( All rights reserved.
cord-103972-kbv9kh6z	2020	We show robustness to (i) different weather controls, (ii) additional fixed effects, (iii) multilevel clustering of standard errors, (iv) different winsorization and interpolation of the raw AQI data, (v) including out-state patients at hospitals, (vi) focusing on states with a long time series only, (vii) using missing values instead of zeros for county-months with no hospital admissions, and (viii) using a linear ordinary least squares instead of a Poisson Pseudo-Maximum Likelihood estimator. We use the standard deviation of the AQI during the influenza season (12.79) as well as the average inpatient hospitalization numbers (3.01) for the calculation of absolute effects based on our Poisson Pseudo-Maximum Likelihood estimation. We estimate the relationship between influenza-related inpatient hospitalizations H cym and the lagged air quality index AQI cym−1 at the county c by calendar month m by year y level using a Poisson model:
cord-251979-j3mme15e	2016	
cord-252293-8286lsof	2018	
cord-252443-lclxrwcm	2012	
cord-252974-pwx27kdi	2007	
cord-253049-vm46wq1m	2020	
cord-253083-4mk5u0wg	2014	Emergence of avian influenza A(H7N9) virus causing severe human illness-China Epidemiology of human infections with avian influenza A(H7N9) virus in China Case control study of risk factors for avian influenza A (H5N1) disease Hong Kong 1997 Case-control study of risk factors for human infection with influenza A(H7N9) virus in Jiangsu Province, China Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome Human infection with avian influenza A H7N9 virus: an assessment of clinical severity Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection Surveillance of avian influenza A(H7N9) virus infection in humans and detection of the first imported human case in Taiwan
cord-253143-73dsc6q3	2010	
cord-254117-2ttwaegh	2011	
cord-255181-du6rqc6i	2005	This review addresses a number of potential risk factors and their implications for activities with viral vectors from the perspective of cross‐species transfer of viruses in nature, with emphasis on the occurrence of host‐range mutants resulting from either cell culture or tropism engineering. The HIV virus and contemporary human influenza viruses are prominent examples of viruses that have crossed the species barrier and established themselves permanently in the human population without further dependence on the presence of the original animal host reservoir. The emergence of HIV exemplifies how multiple independent cross-species transmissions of simian viruses that are not associated with disease in their natural hosts eventually resulted in the establishment of two types of HIV in the human population. The following examples demonstrate that upon persistent infection and passage in cell culture, cross-species transmissibility may be promoted by selection of virus variants with an altered host range. Adaptation in cell culture may result in changes in receptor specificity and tropism, and leads to the emergence of host-range mutant viruses.
cord-255807-7goz1agp	2003	
cord-256432-53l24le2	2020	The entire frame is an analysis of disaster events from a macro perspective, including "causes," "development," "response," "event impact" and "risk information dissemination." Then, through literature research and expert consultation, the researchers summarized the concept of the communication framework and initially formed its content suitable for the influenza epidemic. We believe that the information provided by these 28 respondents can meet the sample size required for the analysis of this study, because the purpose of mental model study is not to use statistical methods to analyze the distribution of some risk cognition in the population, but to find out which concepts or beliefs, are "out there" with some reasonable frequency, 3 so as to help government departments identify what should be focused on when developing guidance programs and health education materials for this population.
cord-257489-ruf4rzxm	2007	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. 13 Korea shows relatively high influenza vaccine distribution rate, however, exact vaccination coverage among total population or priority group have not yet been studied. The coverage rates for influenza vaccination were 34.3%, 61.3%, 79.7%, and 54.9% among total adult population, high risk group, persons aged !65 years and persons with comorbid conditions, respectively (Table 1) . The most common reasons for vaccination were not different in high risk group, however, ''have interest in vaccination because of bad health status'' showed higher rank (18.4%) than the total population.
cord-257491-tsdwsyjs	2016	In the first 3 months of the epidemic season 2015/2016 (October-December, 2015) there were 406 more cases of confirmed and suspected cases of influenza in children up to 14 years of age compared with the preceding epidemic season in Poland (NIPH-NIH 2016). In the present study, therefore, we seek to determine the overall activity of influenza and influenza-like viruses in children under 14 years of age in the epidemic season 2015/2016 in Poland. There were 3376 specimens taken from children up to 14 years of age tested in the epidemic season 2015/2016 in Poland. There were 8542 specimens tested during the epidemic season 2015/2016, in Poland, of which 3376 were collected from children 0-14 years of age. The results also confirm the frequent presence of influenza and influenza-like viruses in children aged 0-14 years.
cord-258021-xhx74vr6	2016	
cord-258270-67f5z8et	2014	
cord-258366-fu9b446y	2012	At Hospital das Clinicas, University of Sã o Paulo School of Medical Sciences, a previous study showed a 34% compliance with influenza vaccination among HCWs. In the mentioned study, the main reasons for non-compliance were the perception of vaccine inefficacy and the fear of adverse reactions [4] . To diminish the arguments of fear of adverse events or perception of vaccine inefficacy, this prospective study was conducted to demonstrate to a subset of HCWs from our hospital, that severe adverse events following influenza vaccination are rare and the episodes of respiratory symptoms occurring in the first four months after vaccination are generally caused by other respiratory viruses and not by influenza virus. As expected, no severe adverse event was observed in the present study, and the events more frequently reported, such as headache, myalgia and malaise could be related to influenza vaccine itself as well as to other causes, given their unspecificity.
cord-258496-h264umt1	2014	CONCLUSION: Our results demonstrate that a decrease rather than low temperature and humidity per se during the preceding three days increase the risk of influenza episodes in a cold climate. Studies from temperate and tropical climates have demonstrated that low temperature [4] and humidity increase the risk of seasonal influenza onset in the winter [5] [6] [7] [8] . Our previous study conducted in a northern climate demonstrated that the occurrence of respiratory tract infection is associated with both low temperature and humidity [15] . The objective of the present study was to examine the relations between temperature, humidity and the risk of influenza virus infections in a subarctic climatic zone in Northern Finland. Our hypothesis was that decreased daily temperature and humidity during outdoor training and associated with physical exercise would increase the risk of influenza A and B virus infection. Cold temperature and low humidity are associated with increased occurrence of respiratory tract infections
cord-258781-peppszqx	2011	The findings of the review may be able to help inform policy statements on the effectiveness of mass gathering restriction interventions that may be deployed to help reduce influenza virus spread during a pandemic. The other five observational studies were similarly designed, involving groups of intending Hajj pilgrims who were recruited in their home regions or countries prior to the event, and then re-assessed This was a well-organized systematic prospective influenza surveillance program, described by the authors as the first of its type at a large Games event Limitations include: A number of studies [18] [19] [20] [21] [22] have consistently demonstrated, over a number of years, that respiratory virus transmission occurs amongst pilgrims attending the annual Hajj in Saudi Arabia, and it is recognized as an issue of international public health significance [43] [44] [45] [46] that could be particularly important in a pandemic situation.
cord-260191-0u0pu0br	2004	
cord-260525-bohv78hi	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. Patients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, increased red blood cell distribution width, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin. Overall, our study reveals significant differences in the laboratory parameters between the hospitalized COVID-19 and influenza patients. Compared to influenza patients, the most significant differences over the course of 14 days of hospitalization in COVID-19 patients were worsening anemia, worsening leukocytosis, and an increase in D-dimer, BUN, and ALT. Instead of comparing clinical endpoints to evaluate risks as performed in most of the published studies, we stratified the hospitalized COVID-19 patients through clustering of their laboratory results that were most significantly different from influenza patients (i.e. complete blood count, D-dimer, BUN, and ALT) during the first 14 days of hospitalization.
cord-260690-h5pjv2dw	2004	
cord-260728-4w23kwzu	2016	
cord-261241-eqf6ame6	2017	
cord-261282-r1nprlne	2016	[13] examined clinical trial data of 3744 adult ILI cases (defined as body temperature 537·8°C or patients subjective feeling of feverishness) and of those 2470 (66%) had laboratory-confirmed influenza. The aim of this study was to compare the rates of fever in adult subjects with confirmed influenza and other respiratory virus infections and examine predictors of fever. Rates of fever in influenza and other viral respiratory infections in this study were lower compared to other studies which report fever in around 50-70% adult cases [1, 5, 13, 15] . Clinical signs and symptoms are less studied for other viral respiratory infections, but available evidence suggests that other respiratory viruses are associated with a lower rate of fever compared to influenza [5, [30] [31] [32] [33] . Compared to children, this study shows that adults are less likely to have fever with a respiratory viral infection, even influenza.
cord-262201-4pab383g	2010	RESULTS: Antiwei increased patients'' recovery by 17% (P < 0.001), and reduced the severity of illness measured by the median symptom score by 50% (P < 0.001) in both the influenza-like and the influenza-confirmed populations, compared to placebo. The influenza-confirmed patients reported reductions in the severity of fever (P = 0.002), cough (P = 0.023) and expectoration (P = 0.004) after one-day of treatment with Antiwei, compared to placebo. 14 Therefore, a prospective, multi-center, randomized, double-blind, placebo-controlled clinical trial was undertaken to investigate the efficacy and safety of Antiwei granule for the treatment of naturally acquired influenza in humans. The primary endpoints were severity of illness (measured by the mean symptom scores for the whole treatment period) and the number of recovered patients in the intention-to treat and influenza-confirmed populations. For patients with influenza-like illness, the number of recovered patients after three days of treatment in the Antiwei group increased 17% and the severity of symptoms was significantly reduced 50% compared to placebo.
cord-263277-m4too6ob	2020	
cord-263353-4mnsjbib	2014	
cord-263464-fdosch11	2019	
cord-264335-c2hfh3dq	2009	In order to detect and then type influenza A viruses most laboratories use a two tier testing system comprising of a universal influenza A screening assay complemented with a suite of subtyping assays that determine whether the sample is seasonal influenza A (human H1N1 and H3N2), avian H5N1 or the influenza A/H1N1/2009 virus. This article describes the development of a multiplex real-time reverse transcription polymerase chain reaction (rtPCR) that allows universal detection of all influenza A viruses and simultaneously subtypes all that are influenza A/H1N1/2009. Use of this assay will allow laboratories to screen respiratory samples for influenza A/H1N1/2009 virus in a rapid and cost effective format, ensuring that typing methods for seasonal and avian viruses are used on a smaller subset of samples. This article describes the development of a rapid, specific and sensitive multiplex rtPCR assay that detects all influenza A types and simultaneously identifies samples that contain the pandemic influenza A/H1N1/2009 virus.
cord-265138-i5m3ax7g	2012	METHODS: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. CONCLUSIONS: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. Four model selection criteria were considered in this study: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV). Two recent studies in Canada and Hong Kong have demonstrated the estimates of influenza-associated hospitalization derived from Poisson regression models reasonably matched the numbers of patients with laboratory confirmed influenza infections [17, 29] .
cord-265751-q1ecpfyg	2017	
cord-266100-1rktb6yq	2012	Therefore, we hypothesized that inhaled nitric oxide (iNO) would increase survival in vivo by reducing the viral load in C57Bl/6 mice infected with a lethal dose of influenza A/WSN/33 (H1N1; WSN/33) virus. Therefore, both continuous and intermittent iNO administration failed to reduce lung viral load of infected mice, compared to infected control mice administered compressed room air. iNO administered to influenza infected mice in this manner, either prophylactically or therapeutically, failed to improve survival of infected mice, change the course of weight loss, or decrease the lung viral load, compared to control mice receiving compressed air. In conclusion, despite the demonstrated antimicrobial activity of NO against influenza A virus in vitro, the results of this study do not support the use of iNO as a prophylactic or treatment strategy to reduce viral burden or improve clinical outcome in severe influenza in vivo.
cord-266204-ipa017wz	2018	This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing "downstream" adaptive humoral and cellular responses to infectious pathogens and vaccines. A decade ago, we described the idea of vaccinomics and adversomics, based on the immune response network theory [5, 6] , which utilizes immunogenetics/imunogenomics and systems biology approaches to understand the basis for inter-individual variations in vaccineinduced immune responses in humans, as well as the basis for adverse side effects from vaccines [7] . Published data reveal that innate and adaptive immunity is decreased with age, but the systems-level mechanisms for these findings are unclear [66, 68] , particularly in regard to influenza and other viral vaccine responses where the morbidity, mortality, and associated healthcare costs are greater in older individuals [11] .
cord-268296-w0i7rhru	2015	14 Data on laboratory surveillance of the influenza B virus in Brazil are limited, specifically data on the burden of disease and circulation patterns of influenza B lineages. The present integrative review of publicly available data aims to consolidate findings on the pattern of influenza B occurrence in Brazil to have a better understanding of influenza B epidemiology and its relevance to seasonal vaccine composition. We referred to international data sources to check WHO recommendations on the vaccine composition in the Southern hemisphere, 18 and information on circulating influenza lineages for Brazil, the South America region and globally from the WHO/FluNet database which provides data through its network -Global Influenza Surveillance and Response System (GISRS) laboratories. The three reviewed abstracts, which specifically report findings on influenza B mismatch, corroborate this unpredictable behavior of influenza B disease in Brazil for many other seasons for which data were not available in the International Epidemiological surveillance data.
cord-268369-yj7m0n0f	2006	The influenza hemagglutinin protein (HA), the active ingredient in the current vaccine, can be expressed in insect cells using the baculovirus expression vector system and purified rapidly. On the other hand, the recombinant protein-based approach involves production of viral antigens such as HA and NA in cell culture with recombinant DNA technology and utilization of the purified antigens as the active ingredients in the vaccine. The rHA influenza vaccines developed using the baculovirus-insect cell expression system has been tested in several Phase I and Phase II human clinical trials involving over 1200 subjects that demonstrated safety, immunogenicity and efficacy [19] [20] [21] [22] [23] . On the other hand, most of RBCs were bound to the insect cells infected with baculovirus containing the HA gene derived from influenza strain A/New Caledonia/20/99 (H1N1) (Fig. 1b) .
cord-268593-rvxxv1dn	2015	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. While influenza A and B virus contain the two glycoproteins Hemagglutinin (HA) and Neuraminidase (NA) inserted into the viral membrane, influenza C virus possesses only one spike designated Hemagglutinin-Esterase-Fusion (HEF) protein which combines the functions of both HA and NA (Herrler et al., 1988a; Herrler and Klenk, 1991) . Although there is only 12% amino acid identity between HA and HEF, the overall structure of both molecules as well as folds of individual segments are quite similar, except an additional bulge, which is located at the lower part of the globular domain and contains the esterase region that is not present in HA (Fig. 3) .
cord-268693-td6kvmlq	2020	
cord-269324-zh1a3gwh	2008	
cord-269623-9pxdeva3	2003	The contrast between recent cases of H5N1 infection, associated with high mortality, and the typically mild, self-limiting nature of human infections with avian H7N7 and H9N2 influenza shows the gaps in our understanding of molecular correlates of pathogenicity and underlines the need for continuing international research into pandemic influenza. We gave priority to randomised controlled trials when available, to larger studies, articles published in high-impact journals that have a wide readership, and the systematic review and economic decision modelling, for the prevention and treatment of influenza, commissioned by the Health Technology Assessment Programme on behalf of the National Institute of Clinical Excellence. A meta-analysis of reports published before 2001 showed that vaccination reduces numbers of cases of influenza-like illness by 35%, hospital admissions for pneumonia and influenza by 47%, and all-cause mortality by 50%.
cord-270703-c8mv2eve	2018	We implemented a real-time report to distribute respiratory pathogen data for our 8-hospital system to anyone with an Internet connection and a web browser. We implemented a real-time report to distribute respiratory pathogen data for our 8-hospital system to anyone with an Internet connection and a web browser. To address these local needs in a major US metropolitan area, our clinical microbiology laboratory implemented an online dashboard to distribute respiratory pathogen data for our 8-hospital system to clinicians, epidemiologists, infection control practitioners, system leadership, and the public. Development of this report began in the Fall 2017, before the respiratory virus season, during which influenza reached an epidemic status across the United States that resulted in supply shortages, testing difficulties, and a widespread public health crisis [4, 5] . In summary, our microbiology laboratory implemented a near real-time Internet report to distribute respiratory pathogen data for our 8-hospital system to clinicians, hospital epidemiologists, infection control committees, system leadership, and the public.
cord-270772-zshjrc87	2015	
cord-270910-xb746mv5	2020	
cord-271172-y48dovux	1998	
cord-272655-qeojdpez	2015	OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Under this initiative, countries have developed surveillance systems by following cases of influenza-like illness and severe acute respiratory infections (SARIs), which are clinically diagnosed among patients with fever, coughing or sore throat, difficulty breathing and the need for hospitalization [3] . In our study, viruses were identified as the most frequent causal agents of SARI requiring hospitalization in 2012, with most cases showing a high rate of viral co-infection, a high degree of morbidity, prolonged hospital stays and frequent needs for ICU management and mechanical ventilation.
cord-273147-24fkaqlz	2006	METHODS AND FINDINGS: We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. In this study, we characterize the spatial variability in the inter-regional timing of the seasonal component of influenza mortality across the United States and assess its relationship to airline volume. For each influenza year, coincidence in the timing of seasonal influenza mortality across geographic regions was estimated from the phase shift with a national seasonal curve, derived by summing of all city data and filtering.
cord-273907-58jufmx7	2020	
cord-275150-d63noia4	2017	
cord-275355-4izc5jxs	2005	in this issue of the Journal of Infectious Diseases [1] , and the recent instances of cross-species transmission that caused human disease [2] raise fundamental questions regarding the routes of transmission of avian viruses to and between humans, possible differences in transmission patterns between human and avian influenza viruses, and implications for prevention in those occupationally exposed to infected animals and also in health care, household, and community settings. The findings that seropositivity occurs in small numbers of poultry workers exposed during outbreaks of illness in poultry caused by some avian strains (H7N7, H7N3, and H5N1) but not others (H7N1 and H5N2) argue for actual infection and support the notion that some avian influenza viruses are more likely than others to infect humans [1] . Most cases of human infection due to avian influenza viruses have involved close contact with infected poultry, particularly ill or dying chickens.
cord-275462-7a55odok	2009	
cord-275814-seirbkiq	2014	A two-city mathematical model involving a pandemic strain is used to derive the basic reproduction number ( R 0 ), which determines if the disease will spread and persist ( R 0 > 1 ) or go extinct ( R 0 < 1 ). Real air travel data is used to model the disease spread by individuals who are susceptible to or are infected with pandemic avian influenza. Real air travel data is used to model the disease spread by individuals who are susceptible to or are infected with pandemic avian influenza. We only consider the air travel of susceptible and infected humans with pandemic avian influenza because the infected individuals can only contract the disease from domestic birds (that do not travel). HPAI and pandemic avian influenza both become extinct in the bird and human populations when all the reproduction numbers are less than one.
cord-276015-id15u3br	2016	This study compared the efficacy and safety of inosine pranobex versus placebo in subjects with clinically diagnosed influenza-like illness, including subjects with laboratory-confirmed acute respiratory viral infections. In the subgroup analysis for subjects less than 50 years of age, statistically significant differences in time to resolution of influenza-like symptoms that favoured the inosine pranobex group over the placebo group were observed in those without related ongoing disease and those who were non-obese (BMI <30 kg/m(2)). CONCLUSIONS: The study results indicate the safety of inosine pranobex for the treatment of subjects with confirmed acute respiratory viral infections and confirm the efficacy of inosine pranobex versus placebo in healthy non-obese subjects less than 50 years of age with clinically diagnosed influenza-like illnesses.
cord-276037-0bxwv6b7	2011	Therefore, we investigated the safety of an inactivated monovalent H1N1 pandemic influenza vaccine METHODS: We focused on the H1N1 pandemic influenza vaccine Pandemrix(® )and applied a self reporting questionnaire in a population of healthcare workers (HCWs) and medical students at a major university hospital. Due to a special debate on the safety of the pandemic influenza vaccines [18] , it was the objective of the present study to analyse the safety using a self reporting questionnaire approach in the acute event of a pandemic and a novel vaccine which was debated for its safety by the general population and healthcare worders (HCWs). In the situation of a pandemic and the acute supply of a novel vaccine which included the immunologic adjuvant AS03 and thiomersal (thimerosal), and a public debate about the safety of this vaccine, the sample selection method based on the assessment of all individuals that were vaccinated after informed consent at the occupational medicine centre of Germany largest university hospital.
cord-276577-06boh550	2009	METHODS AND FINDINGS: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV), adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. The RVDSS collects, collates, and reports weekly data from participating laboratories on the number of tests performed and the number of specimens confirmed positive for influenza, respiratory syncytial virus (RSV), para-influenza virus (PIV), and adenovirus. The overall model fit, and the general consistency of the sensitivity estimates, suggests that these many respiratory viruses were reasonably accounted for by the seasonal baseline and that the strong association between the number of influenza positive and influenza negative tests on a weekly basis is indicative of a significant number of false negative results, rather than the activity of another virus or viruses exactly synchronous with influenza.
cord-277217-jh4qmoso	2013	
cord-277970-sb1wjd3b	2020	
cord-278508-h145cxlp	2015	
cord-278554-rg92gcc6	2015	
cord-278807-p1crrb8n	2016	
cord-279615-yne753y6	2016	
cord-280218-zwjrcaab	2014	
cord-281228-8kqohdcr	2020	
cord-282085-r3w90vg8	2020	This study uses measured amounts of SARS-CoV-2 in the air of a hospital room with COVID-19 patients from a published and peer-reviewed study and known Influenza A challenge doses from a published and peer-reviewed study and known ASHRAE Office Ventilation standards and an Outdoor Air Exchange model to estimate the time necessary to cause various exposure levels and resulting infection potential in various indoor and outdoor settings of both Influenza A and COVID-19. The estimates in this study also present an initial framework and specific quantitative examples for better understanding of the effects of ventilation on aerosolized transmission, and the immunology related to challenge doses, and the potential for low-level viral load exposure to result in some level of immunity without symptoms of illness (asymptomatic infection).
cord-282140-teplpmi6	2016	
cord-283537-49ic7p3u	2015	
cord-284087-g2jfnxja	2013	
cord-285856-0sw3wt1i	2009	
cord-286368-kdwh4hgf	2017	Observational studies have shown that treatment with a neuraminidase inhibitor (NAI) for adults hospitalized with severe influenza is associated with lower mortality and better clinical outcomes, especially when administered early in the course of illness. The global circulation of oseltamivir-resistant seasonal influenza, the emergence of A(H1N1)pdm09 virus in 2009 followed by its continual circulation, 6 the rising number of A(H7N9) infections in humans 2 and the ongoing spread of A(H5N8) in recent months in the poultry populations in many countries in Asia, Africa, Europe and Middle East with pandemic potential 7 all point to an urgent need for developing more effective antiviral therapies to reduce morbidity and mortality. Human infections with a novel avian influenza A (H7N9) virus were first reported in China in March 2013 in patients hospitalized with severe pneumonia.
cord-287554-2lqy2ix9	2017	
cord-287824-zg5akivn	2020	title: Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections. In the recent years, an 66 increasing trend of influenza outbreaks have been observed, prompting medical researchers to 67 design and develop suitable vaccines and novel therapeutic modalities [10] . Targeting 411 neutrophils using novel drug delivery systems in chronic respiratory diseases Increasing 440 complexity and interactions of oxidative stress in chronic respiratory diseases: An 441 emerging need for novel drug delivery systems Interactions 501 with the macrophages: An emerging targeted approach using novel drug delivery 502 systems in respiratory diseases Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: 537 Another emerging application of nanomedicine
cord-288238-36hiiw91	2020	It is also reported that influenza infection significantly increases ROS production by inducing Nox4, and the proliferation of this virus in lung epithelial cells is dependent on redox-sensitive pathways activated by Nox4-derived ROS [16] . IFN can also exert its function on metabolic changes by producing several mediators including indoleamine-2,3-dioxygenase (IDO) and nitric oxide (NO), both of which appear to have either an inducible or an inhibitory role in viral replication [33] . In addition, increased temperature of cells during infection (which could be the result of virus replication and fever) causes heat stress which in turn can considerably downregulate carnitine palmitoyltransferase II (CPT II) activity and reduce the β-oxidation and ATP levels in fibroblasts of influenza-associated encephalopathy patients and healthy volunteers [110] . Through enhancing the activity of the mTORC1 complex, the influenza virus strengthens several metabolic pathways, including glycolysis, glutaminolysis, pentose phosphate, and fatty acid synthesis, to provide more ATP and structural materials for viral replication.
cord-288487-hs3wfffs	2008	
cord-288938-4bheqtk5	2019	
cord-289285-aof7xy13	2011	
cord-289439-jrvl0ykn	2018	
cord-290004-v3ruj5bq	2020	
cord-290031-vffa1bu0	2020	
cord-290100-wnjjqqn5	2012	
cord-290352-0pc5eji4	2005	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. However, occurrences of direct bird-to-human transmission of avian influenza viruses have increasingly been reported in recent years, culminating in the ongoing outbreak of influenza A (H5N1) among poultry in several Asian countries with associated human infections. The "Asian influenza" pandemic of 1957 was caused by an H2N2 virus that had acquired three genes (H2, N2, and PB1) from avian viruses infecting wild ducks, in a backbone of the circulating H1N1 human influenza strain. Furthermore, these infections were associated with severe hemorrhagic pneumonia and the induction of high levels of macrophage-derived cytokines and chemokines, strikingly reminiscent of clinical observations in humans during the Spanish flu pandemic, as well as of recent in vitro and in vivo observations of infections with highly pathogenic avian influenza H5N1 viruses (Cheung et al., 2002; Oxford, 2000; Peiris et al., 2004; To et al., 2001) .
cord-292528-8kdhf123	2009	
cord-292709-4hn55wui	2017	
cord-292794-okh6i4l1	2012	Results demonstrated that there was no detectable virus load in all the vaccine-immunized mice, while empty vector control group showed high lung viral titers ( Figure 4 ). Results indicated that all the mice that had been vaccinated with MHa had a detectable virus level, although showed a reduction in mean viral titers in both challenge groups compared with vector control, the reduction did not reach significance (p = 0.06 for rPan09 group and p = 0.67 for G11 group, Figure 4 ). The present study lays the foundation for universal swine influenza vaccine development, and call for further investigations in which the heterologous immune response should be further enhanced, such as the addition of molecular adjuvants [31, 32] and/or more copies of conserved viral protein encoding genes [33] , and the usage of DNA-prime protein/virus-boost immunization schedule [34, 35] .
cord-292856-7hjzzxtm	2012	
cord-292963-8wzyfb2j	2015	
cord-293234-ouykx6g5	2012	
cord-293299-gdew0ueo	1974	A long historical tradition for the use of livevirus vaccines in the Soviet Union dates from Smorodintsev''s experimental infection of volunteers with influenza virus in 1937 [2] . Since registered morbidity rather than a more direct measure of real influenza-ARD morbidity is used, the model probably has more applicability for health planners, who need to anticipate increased requirements for delivery of health care associated with epidemics, and for industrial organizations that face future production losses, than for those concerned with anticipating changes in the health status of the population per se. Although data from the morbidity registration system in the Soviet Union provide the basic information for this model, data from the 52 All-Union reporting centers appear to be used as well, particularly for obtaining early warning of the location of the initial epidemic outbreak in the country.
cord-293472-d3iwlpsr	2012	
cord-294323-mryiqmsw	2018	The wide range of hosts provides influenza A viruses greater chances of genetic re-assortment, leading to the emergence of zoonotic strains and occasional pandemics that have a severe impact on human life. Here, we primarily discuss the pathogenesis of influenza virus type A, its epidemiology, pandemic potential, current status of antiviral drugs and vaccines, and ways to effectively manage the disease during a crisis. A genetic shift occurs when two or more different influenza virus strains infect the same cell in a host, leading to recombination of genetic materials, an event that occasionally generates a new strain with a novel combination of hemagglutinin and neuraminidase. The antiviral drugs currently available against influenza viruses are adamantane derivatives (amantadine and rimantadine) and neuraminidase (NA) inhibitors (zanamivir, oseltamivir and peramivir). Due to the increasing burden of vaccine formulations and cases of antiviral-drug-resistant influenza virus isolates turning up every year, it has become necessary to search for alternatives to the current treatment and prevention strategies.
cord-295531-zojb3cew	2008	Subtypes of influenza A viruses that are prominent in one species may on occasion infect and cause disease in another. Influenza A is a single-stranded RNA virus that causes an acute and highly contagious upper respiratory disease. It was approved in 1966 for chemoprophylaxis and in 1976 for treatment and chemoprophylaxis of influenza type A virus in both adults and children 1 year of age. It was approved in 1993 for the treatment and chemoprophylaxis of influenza A infections in adults and prophylaxis in children. It was approved in 1999 for the treatment of uncomplicated influenza infections in patients aged 1 year. It was approved in 1999 for the treatment of uncomplicated influenza infections in patients aged 1 year. Basic information on the diagnosis, clinical findings, complications, prevention and treatment of influenza, including vaccine safety recommendations, can be found at: http://www3.accessmedicine.com/content.aspx?aID=17572#17572 Information on the common cold and flu can be located at: http://familydoctor.org/517.
cord-296277-paqu1t1e	2016	The basic cohort design Baseline/pre-season phase A baseline visit was made to the household at enrolment, during which a research nurse collected blood samples for serological and T cell analysis from all adults aged 16 years or older. Current work includes an analysis of occupational exposure to pigs as a risk factor for human infection with swine and human influenza viruses; age as a predictor of T cell responses; and a comparison of serological pandemic infection rates from Flu Watch and the Health Survey for England. Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study Natural T Cell Mediated Protection Against Seasonal and Pandemic Influenza: Results of the Flu Watch Cohort Study
cord-296469-h0ma163u	2016	
cord-296935-y77c4ro4	2011	
cord-296998-ep46lzeo	2020	Seasonal influenza remains a major public health problem, responsible for hundreds of thousands of deaths every year, mostly of elderly people. 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. 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. In this way, intranasally administered vaccine resulted in protection against multiple strains of influenza in mice and ferrets, associated with both humoral and cellular responses 36 . Effect of latent cytomegalovirus infection on the antibody response to influenza vaccination: a systematic review and meta-analysis
cord-297022-zs5m36cp	2007	Groll and Thomson''s evaluation of the effectiveness of Ontario''s Universal Influenza Immunization Campaign used per capita cases of laboratory-confirmed influenza. A better measure of viral activity is the proportion of influenza tests positive; whereas the weekly proportion of tests positive was relatively consistent, a marked increase over time in the numbers of laboratory-confirmed cases paralleled an increase in the number of tests performed. Regardless, for evaluating universal influenza immunization program effectiveness, other established and available measures employed in previous studies describing the epidemiology of influenza should be used instead of laboratory data. In their evaluation of Ontario''s Universal Influenza Immunization Campaign, Groll and Thomson state that there is a lack of high-quality influenza outcome data in Ontario, so instead they examined the effectiveness of the program using per capita cases of laboratory-confirmed influenza [1] . A better measure of viral activity is the proportion of influenza tests positive (the number of cases of lab-confirmed influenza divided by the number of tests performed).
cord-297742-0pfrk5uk	2020	METHODS: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza surveillance system (ISS) in Zambia during 2011–2017 using 9 attributes: (i) data quality and completeness, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability, (viii) utility, and (ix) sustainability. The objectives of the Zambia-ISSS were to: (i) monitor the temporal trends of influenza virus circulation; (ii) monitor the circulating influenza virus types and subtypes annually, including pandemic strains; (iii) assess the proportion of patients meeting the ILI and SARI case definition attributable to influenza virus infection; (iv) assess risk factors for influenza-associated severe illness; (v) assess the burden of influenza-associated illness; and (vi) obtain and share clinical samples for annual selection of influenza virus strains for influenza vaccine formulation under the WHO-Global Influenza Surveillance and Response Network.
cord-297829-aynigoud	2014	title: Post-pandemic assessment of public knowledge, behavior, and skill on influenza prevention among the general population of Beijing, China The standardized interview questionnaire was designed to collect the following data: (1) socio-demographic characteristics (gender, age, education, occupation, and general health status); (2) knowledge about the disease and its symptoms; (3) practices towards influenza and people with influenza-like-illness (i.e., avoidance practices, cough etiquette, use of masks, hand washing, being vaccinated, health-seeking behaviors); (4) perceived ability to avoid illness; (5) attitudes towards the vaccine, and (6) comprehension of health materials related to influenza (i.e., medication instructions, educational information about influenza and the vaccine). It was necessary and valuable for us to conduct the study to determine the overall level of influenzarelated health literacy in the general population of Beijing after the 2009 pandemic, data that provide a baseline for influenza prevention and control strategies in the future. 19 In this study, the qualified levels of all three sections (knowledge, behavior, and skill) in the general population were significantly higher (p < 0.001) with a higher level of education, which is similar to the nationwide health literacy level of China.
cord-298216-iq7fenxm	2020	
cord-298551-ua90xoak	2016	The hospital is a tertiary referral center with surgery and a pediatric intensive care unit (PICU) with resources for extracorporeal membrane oxygenation (ECMO), but only children resident in the catchment area were included in the study. The yearly incidence rates in different age groups varied considerably, with median (range) for children <5 years 59 (19Previously known risk factors were found in 312/922 (34% , Table 1 ), the most important being neuromuscular disease (131 cases) and chronic lung disease (40 cases). This is a report of children hospitalized for influenza A or B in a defined population in the northern Stockholm area 1998-2014, covering the pre-pandemic period, including the 2003-2004 outbreak, the 2009 pandemic, and four post-pandemic seasons. In contrast to the known effect of trivalent influenza vaccine (the only one used during the studied period except for the pandemic year) in healthy children >18 months, less is known about its effect in younger children and in those with risk factors.
cord-298776-tjw45t3f	2018	
cord-299207-lw0cv74b	2007	
cord-299359-s8j78naz	2013	
cord-299364-t549rf3o	2015	
cord-299613-5ju5fcf4	2020	In this paper, we review the evidence on the long-run effects on health, labor, and human capital of both historical pandemics (with a focus on the 1918 Influenza Pandemic) and historical recessions (with a focus on the Great Depression). Thus, a historical perspective allows us to use rich data to look at not only the short-term effects of crises like COVID-19 on health, labor, and human capital, but also the long-term and intergenerational impacts along these dimensions for both individuals and the wider economy. To examine how history can inform our view of the coronavirus pandemic and associated policy responses as they relate to long-run wellbeing, we begin in Section II by reviewing the features of COVID-19 that will determine its potential health and economic impacts, and placing these features in historical context.
cord-300311-eah49b3g	2007	Other studies are often based on selected populations with existing symptoms or complications, reflecting only the worst of the spectrum of disease caused by acute respiratory infections [9, [14] [15] [16] [17] ] and thus disregarding their often self-limiting nature. The availability of effective vaccines against the key viruses involved in asthma exacerbations thus could play an important role in its prevention. However, because of a lack of clinical effectiveness, the natural antigenic variations of the influenza virus, and the low average incidence of influenza, cost-effectiveness in children and adults with asthma will not be easily achieved if vaccination has to be delivered annually. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children Effectiveness of influenza vaccine for the prevention of asthma exacerbations Influenza vaccination in patients with asthma: effect on the frequency of upper respiratory tract infections and exacerbations
cord-300900-0wfsr4iw	2020	Trends in influenza and pneumococcal vaccine coverage in Thai patients with type 2 diabetes mellitus 2010-2018: Experience from a tertiary diabetes center in Bangkok BACKGROUND: Routine vaccination is an important part of preventive services in treating patients with type 2 diabetes (T2DM). METHOD: A retrospective study of randomly medical records stratified by 13 diabetologists was conducted in patients with T2DM from 2010-2018 at Theptarin Hospital, a private multi-disciplinary diabetes center in Bangkok. A retrospective study of randomly medical records stratified by 13 diabetologists was conducted in patients with T2DM from 2010-2018 at Theptarin Hospital, a private multi-disciplinary diabetes center in Bangkok. Patients with type 2 diabetes mellitus (T2DM) are a key target of routine annual influenza vaccination and periodically pneumococcal vaccination as epidemiologic studies suggested that these patients are at high risk for complications, hospitalization, and death from influenza and pneumococcal disease [2] .
cord-302141-gd663uag	2020	There are substantial gaps in our knowledge of the impact of severe influenza on perinatal outcomes, especially in low and middle-income countries, but preterm birth, fetal death, infant respiratory infection and hospital admission may be increased. This report therefore recommended the promotion of influenza vaccination to pregnant women at any stage of pregnancy and that influenza should be considered early on presentation to health care facilities in order to test and initiate treatment (10) . Several large prospective cohort studies, predominantly undertaken in the pandemic period, have reported that within the pregnant population there are factors which increase the risk of hospitalization or severe outcomes from influenza (13, 22, 30, 31) . A pooled analysis of three RCTs undertaken in LMIC reported that maternal influenza immunization is also 20% effective at protecting young infants against severe pneumonia (48) and reduces the risk of hospital admission with all cause acute lower respiratory illness by 44% (95% CI 1 -68%) (46) .
cord-302529-43pd2qsp	2013	METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses'' infection during three seasons in Tunisia. A subset of sentinel primary care physicians participating in virological surveillance schemes in the community submits respiratory samples for virological testing from patients presenting in primary health care with an ILI, as well as all regional emergency centres and hospitals that take on surveillance of influenza from community, hospitalized and fatal cases. Phylogenetic analysis of the HA1 nucleotid sequence of 23 influenza A(H1N1)pdm09 viruses from mild, severe (patients hospitalized with severe pneumonia and severe acute respiratory syndrome) and fatal cases, shows that all viruses characterised in Tunisia during season 2009-2010 were outside the seven genetic groups described in the European Centre for Disease Prevention and Control (ECDC) report [19] .
cord-302713-h3aoag4y	2011	title: Clinical and Microbiological Evaluation of Travel‐Associated Respiratory Tract Infections in Travelers Returning From Countries Affected by Pandemic A(H1N1) 2009 Influenza BACKGROUND: Although acute respiratory tract infections (RTI) have been recognized as a significant cause of illness in returning travelers, few studies have specifically evaluated the etiologies of RTI in this population. Patients were included if they presented with signs suggestive of RTI that had occurred during travel or <7 days after their return from countries endemic for influenza virus A(H1N1) 2009. At the virology laboratory, the first step of the diagnostic evaluation was to identify influenza A(H1N1) 2009 virus infection by means of real-time reverse transcription-PCR (RT-PCR), as previously described 11 to assess whether or not the patient should remain isolated. In a study performed at San Francisco University Medical Center during the influenza season, a viral agent was identified (through shell vial assay and PCR) in 103 (39%) of the patients with RTI.
cord-304023-s22wi0t0	2019	METHODS: Influenza surveillance based on a primary care sentinel surveillance, virological indicators systematic sampling of ILI attended and severe influenza confirmed cases (SHLCI) admitted to hospital. CONCLUSIONS: 2017–2018 influenza season was an unusual epidemic season with an early onset, great predominance of influenza B (Yamagata strain) virus with a high hospitalization rate of severe cases among elderly stressing the need to upgrade vaccine uptake in this age group. 4 The 2017-2018 influenza season presented a predominant circulation of influenza virus type B during the first epidemic weeks with a high rate of severe influenza hospitalizations, especially among the elderly. The aim of this work is to describe the 2017-2018 influenza season according to the PIDIRAC Sentinel Influenza Surveillance System and how it affected elderly population in Catalonia despite moderate vaccine coverage among this age group.
cord-304089-u2abo951	2014	
cord-304485-vouu56rr	2020	
cord-304569-o39kl5k4	2015	
cord-304870-j9kadxu9	2016	
cord-305936-tdswzj7r	2018	
cord-306983-6w2fvtfy	2010	Influenza A virus infection resulted in significant increases in TNF-α, IL-6, IL-1β, viral hemagglutininprocessing protease trypsin levels, and viral replication with vascular hyperpermeability in lung and brain in the first 6 days of infection. The present study reports several new observations: (1) proinflammatory cytokines, TNF-a, IL-1b, and IL-6, when upregulated by influenza A virus infection, induce trypsin expression in various organs and human endothelial cells; (2) the upregulated trypsin induces [Ca 2+ ] i mobilization via activation of the PAR-2, followed by loss of zonula occludens-1 and vascular hyperpermeability; (3) inhibitors of NF-kB and activator protein 1 effectively suppress the upregulation of proinflammatory cytokines and trypsin and improve the survival rates of infected mice. The present results allow us to propose a new mechanism of junctional permeability regulation: upregulated trypsin by influenza A virus and/or proinflammatory cytokines induces increase in [Ca 2+ ] i and loss of zonula occludens-1 in endothelial cells via PAR-2 signaling.
cord-307607-8xn9jtmh	2020	
cord-307813-elom30nx	2018	Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses.
cord-307918-8y89p11a	2012	
cord-309381-cb80ntxs	2019	IAV RNAs are mainly recognized by the endosomal, membrane-associated PRR Toll-like receptors (TLRs) 3 (double-stranded RNAs, dsRNAs) or 7/8 (ssRNAs), respectively [50, 51] , by the cytoplasmic PRR retinoic acid-inducible gene I (RIG-I), which detects dsRNA and 5 -triphosphates of the negative ssRNA viral genome [50, 52] , generated during replication of multiple viruses, by the NOD-like receptor family member NOD-, LRR-and pyrin domain-containing 3 (NLRP3), which recognizes various stimuli (see below) [53] and by the absent in melanoma 2 (AIM2) protein, recognizing not well-characterized influenza stimuli [54] . Another important SNP (rs34481144) associated with risk of severe influenza in humans from the United States (US) infected with seasonal IAVs is located in the 5 -UTR of the IFITM3 gene [123, 124] .
cord-309635-1tgovkr7	2020	Hemagglutinin (HA) glycoprotein is an important focus of influenza research due to its role in antigenic drift and shift, as well as its receptor binding and membrane fusion functions, which are indispensable for viral entry. Similarly, RBS of influenza B HA is composed of the 140-loop, 190-helix, and 240-loop, which are structurally equivalent to the 130-loop, 150-loop, and 190-helix Receptor specificity can also continue to evolve when seasonal viruses circulate in the human population, due to natural mutations that are likely a response to immune selection pressure. A broadly neutralizing human monoclonal antibody that recognizes a conserved, novel epitope on the globular head of the influenza H1N1 virus hemagglutinin Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin Design of nanoparticulate group 2 influenza virus hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages
cord-309860-otx45b8x	2012	
cord-310182-muybvyqa	2018	
cord-310956-qwe4ndvb	2011	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. 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. Two surveillance systems were established in Wuxi for influenza-like illness (ILI) and unexplained pneumonia (UP) after the severe acute respiratory syndrome (SARS) outbreak. To further evaluate the effectiveness of these surveillance systems in early warning of influenza epidemics, we monitored ILI data between 2004 and 2008 by both a control chart method and the Serfling method and tested goodness of fit using influenza A (H1N1) data of 2009.
cord-311115-nimxnf6s	2016	title: Antigenic Drift of A/H3N2/Virus and Circulation of Influenza-Like Viruses During the 2014/2015 Influenza Season in Poland During that season, antigenic drift of influenza virus A/H3N2/ occurred causing higher rates of A/H3N2/ infections. Infections caused by influenza-like viruses accounted for 11.2 % (n ¼ 270) of tested specimens. In the epidemic seasons 2013/2014 and 2014/ 2015 in Poland, the number of specimens received from primary care physicians was similar, although the percentage of influenza and influenza-like infection confirmations was 10 % higher in the latter season. In both seasons, in the case of influenza-like viruses, the predominant virus was RSV. In the 2014/2015 season, antigenic drift of the subtype A/H3N2/ decreased the effectiveness of vaccine against influenza. Evaluation of the activity of influenza and influenza-like viruses in the epidemic season Recommended composition of influenza virus vaccines for use in the 2014-2015 northern hemisphere influenza season
cord-312461-5qzpo6l1	2019	A substantial proportion of pandemic and biological threat preparedness activities have focused on list-based approaches that were in part based on pandemic influenzas of the past, historical biological weapon development programs, or recent outbreaks of emerging infectious diseases (e.g., SARS, MERS, Ebola) (Centers for Disease Control and Prevention 2017; Casadevall and Relman 2010) . Cultivating and maintaining expertise in the epidemiology, surveillance, and pathogenicity of all classes of microbes, with explicit incorporation of a One Health approach-which incorporates and integrates information from infectious diseases of plants, amphibians, and reptiles-will help foster the broad capacities needed for emerging pandemic and global catastrophic biological risks. Pathogen-based lists, both USA and global, based on influenza precedents, historical biological weapon programs, and emerging infectious diseases were responsible for galvanizing early activities in the field of pandemic preparedness and have helped drive many important contributions.
cord-312493-wbhji81g	2013	
cord-313062-lpxmmbpy	2019	PURPOSE: To compare the frequency and the severity of influenza and respiratory syncytial viruses (RSV) infections among children < 24 months hospitalized with respiratory symptoms. CONCLUSION: Even during peak weeks of influenza season, we found a higher burden and severity of RSV compared with influenza virus disease in hospitalized children < 24 months. The aim of this study is to compare the frequency and disease severity of influenza and RSV infections among children < 24 months hospitalized with respiratory symptoms during the peaks of five influenza seasons. In the province of Quebec, Canada, a prospective surveillance study with virologic assessment for influenza and other respiratory viruses was conducted during the peak weeks of influenza circulation among patients admitted for acute respiratory symptoms to four acute-care hospitals since 2012-2013. In conclusion, even during the peak weeks of influenza, more than half of hospitalizations for respiratory infections in children < 2 years of age was due to RSV, with a clinical course more severe than influenza notably among infants < 3 months.
cord-313693-qmkrn7pr	2010	
cord-314607-bcocsjij	2011	
cord-315339-dcui85lw	2015	
cord-316217-ynh8d853	2019	
cord-318556-a28bowqy	2017	Relatively recently, the test-negative case-control studies have been introduced to assess seasonal influenza vaccine effectiveness (SIVE), and despite some limitations, they are currently considered to be the most accurate and efficient way to monitor SIVE. Patients were eligible to be included in the study when they were hospitalised for at least 24 hours, but not longer than 48 hours, had a swab taken ≤7 days after self-reported disease onset, did not test positive and were not hospitalised for any influenza virus in the current season before the inclusion, and were suffering from SARI with at least one of the systemic symptoms (fever, malaise, headache and myalgia) or deterioration of general condition or deterioration of functional status, and at least one of the respiratory symptoms (cough, sore throat and shortness of breath). This study aimed to estimate SIVE against laboratory-confirmed influenza virus infection in patients admitted to the hospital due to SARI in Lithuania during the 2015-2016 season.
cord-318696-jheb2fnn	2012	
cord-318753-ribybqfo	2015	
cord-322082-80ym2rsq	2020	
cord-322906-zef971xp	2020	Since weather regimes such as Cyprus Lows are more robustly predicted in weather and climate models than individual climate variables, we conclude that the weather regime approach can be used to develop tools for estimating the compatibility of the transmission environment for Influenza occurrence in a warming world. The purpose of J o u r n a l P r e -p r o o f Journal Pre-proof this study is to investigate the potential link between weather regime occurrences and climate sensitive infectious diseases, and discuss in how far this relationship can help to inform decisions in the health sector. As a case study, the weekly occurrences of an Eastern Mediterranean weather regime -Cyprus Lows -together with precipitation, temperature and humidity, are related to seasonal Influenza in Israel, the Palestinian Authority and Jordan.
cord-323987-gh1m05gi	2018	RIDTs with digital readout systems showed many similarities to conventional assays like small sample volume (less than 150 µL) and short analysis time (around 15 min) but exhibited much better sensitivities, even one order of magnitude lower limits of detection (LODs). Among methods mentioned, general diagnostic tests for influenza base on virus culture (conventional and shellvial), detection of viral nucleic acid (PCR) or antigens (by neuraminidase enzymatic activity, fluorescent antibody or enzyme/optical immunoassay) and serologic tests. Main trends for influenza virus detection are: (I) modifications of traditional ''gold star'' methods like PCR, RIDTs, ELISA what results in analysis time shortening, costs lowering, LOD and limit of quantification (LOQ) improvement, (II) conjugating of traditional methods and creating new platforms, micro-biochips and others, (III) introducing known solutions to new ones, like smartphone-based analysis control with results data insertion into Google Maps, (IV) reuse of the functions of known devices, like glucometer, smartphone cameras, (V) the most common used detection methods: spectral/optical, electrical, (VI) and entirely new approaches.
cord-324001-m7ys95z7	2010	
cord-324007-hapzf0fl	2009	
cord-324181-nyrpg3ud	2020	title: Baloxavir Marboxil Single-dose Treatment in Influenza-infected Children: A Randomized, Double-blind, Active Controlled Phase 3 Safety and Efficacy Trial (miniSTONE-2) 19, 20 We report the safety and efficacy results of single oral dose baloxavir treatment in otherwise healthy children 1-<12 years old with acute influenza from miniSTONE-2 (Clinicaltrials.gov identifier: NCT03629184), a phase III, randomized, active controlled trial. This was a global, multicenter, double-blind, randomized, active controlled trial of the safety, pharmacokinetics and efficacy of a single oral dose of baloxavir versus twice-daily (for 5 days) oral oseltamivir, in otherwise healthy children with influenza. Parents completed the Canadian Acute Respiratory Illness and Flu Scale (CARIFS) 22 questionnaire at scheduled visits (day [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] , and responses were used to measure secondary efficacy endpoints including time to alleviation of signs and symptoms (TTASS) of influenza [defined as when a score of 0 (no problem) or 1 (minor problem) was reported for cough and nasal symptoms on the CARIFS questionnaire, return to normal health and activity, and return to afebrile state (tympanic temperature ≤37.2°C), remaining for at least 21.5 hours].
cord-324301-bzrh2fni	2005	
cord-325141-x3txhjkr	2020	
cord-325197-j1uo8qmf	2020	Viruses causing severe pulmonary illness can use epigenetic-regulated mechanisms during host–pathogen interaction to interfere with innate and adaptive immunity, adequacy of inflammatory response, and overall outcome of viral infections. In this article, we provide an update on epigenetic-sensitive mechanisms and repurposed drugs interfering with epigenetic pathways which may be clinically suitable for risk stratification and beneficial for treatment of patients affected by severe viral respiratory infections. The goal of the review was to provide an appropriate pathogenic scenario in which epigenetic-sensitive mechanisms and epidrugs may be clinically useful to stratify risk and treatment of patients in ICU affected by severe viral respiratory infections. Here, we give an update on clinical evidence about the usefulness of novel and FDA-approved drugs interfering with epigenetic pathways, which were applied to ICU patients affected by highly pathogenic strains of influenza virus and CoV, with a particular interest about the novel SARS-CoV-2 (Table 4 ).
cord-325325-xw7627x9	2007	While the clock is still ticking towards what seems to be inevitable pandemic influenza, on April 17, 2007 the U.S. Food and Drug Administration (FDA) approved the first vaccine against the avian influenza virus H5N1 for humans at high risk. While the clock is still ticking towards what seems to be inevitable pandemic influenza, on April 17, 2007 the U.S. Food and Drug Administration (FDA) approved the first vaccine against the avian influenza virus H5N1 for humans at high risk. [8] [9] [10] [11] The 1957 pandemic was caused by the H2N2 subtype, a product of genetic reassortment in hosts infected with both an avian and human influenza virus. Although immunization with human influenza vaccine will not protect against avian influenza strains, it should be considered in poultry workers, and also be given to those traveling to affected areas, two weeks ahead of departure, to prevent co-infection and reassortment.
cord-326160-mf0vh6iu	2014	Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. To elucidate global host responses specifically associated with sites of virus-induced airway injury in influenza virus A/Anhui/1/2013-infected macaques, we used microarrays to assess transcriptional profiles induced in lung lesions compared to the adjacent lung tissue. We identified ten compounds in IPA (Table 1) , four of which were perturbagens listed in CMap. We identified two compounds that met our criteria in IPA and CMap, rosiglitazone and simvastatin, predicted to have inhibitory effects on pathological host responses associated with lesions in influenza virus A/Anhui/1/2013-infected animals ( Table 1) .
cord-326177-zzsaf3bl	2018	
cord-326614-cik3ino6	2020	These trials include a variety of viral targets, vaccine platforms, and adjuvants to boost the immune response to vaccination. Another vaccine utilized the full-length H5 HA protein in an oral recombinant adenovirus type 4 (Ad4) vectored vaccine, Ad4-H5-Vtn. Three clinical trials have enrolled 313 participants between 18 and 49 years of age to investigate this avian H5 influenza vaccine. Although results for the phase II trial have not been posted, a press release from Novavax stated that NanoFlu induced superior HAI antibody responses against homologous and drifted strains compared to the seasonal influenza vaccine. Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: Study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: A phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults
cord-326960-9phlylce	2015	
cord-327180-yw8rzrb7	2009	
cord-327516-i25whxt2	2018	
cord-327819-7p05jk1h	2004	
cord-328290-kbysppgb	2015	
cord-328525-80xk3gln	2018	
cord-328979-xfze12ah	2019	Collecting specimens within a short time from the onset of symptoms still maximizes the likelihood of accurate and timely identification of viruses associated with a respiratory illness for studies of transmission and vaccine effectiveness. While respiratory virus infections in general could be studied, the primary objective was to estimate the effectiveness of influenza vaccines using a cohort design for comparison with studies using the testnegative design (TND). With additional funding, we have expanded on these original aims by collecting blood specimens for studies of antibody-mediated Households 328 213 321 232 340 227 Participants 1441 943 1426 1049 1431 996 Influenza-positive individuals 125 32 111 50 202 38 Influenza-positive specimens 130 32 117 52 210 40 Strain A c 86 23 69 48 166 30 H1N1pdm09 27 1 3 47 0 28 H3N2 59 22 66 1 immunity, extending ARI surveillance year-round, and incorporating laboratory testing for other respiratory viruses.
cord-329653-5nkrrqqw	2011	In 2004, after the SARS experience, the World Health Organization (WHO) identified the essential and desirable features of pandemic plans, which included: (i) preparation for surveillance; (ii) investigation of cases; (iii) treatment modalities; (iv) prevention of community spread; (v) maintenance of essential services; (vi) research and evaluation, and implementation; and (vii) testing and revision of the plan. These included calling for streamlined decision making processes, flexible response according to disease severity and local resources, improved communications, public health education, a national surveillance framework, clarification of quarantine, border control, and emergency legislation, and involvement of primary care providers in planning. Public health challenges include developing means of increasing acceptance of influenza vaccination by both the general public and healthcare workers, provision of targeted education for the indigenous population and other at-risk groups, improving public knowledge of social distancing and personal hygiene measures in the prevention of transmission, and improving dissemination of information during a pandemic, especially via the media.
cord-330512-nu8q72l9	2013	
cord-331148-40gvay7i	2018	Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. The results of the logistic regression analysis on the risk factors associated with influenza A(H1N1)pdm09-related complications and pneumonia are shown in Table 4 , and respiratory failure with mechanical ventilation and ARDS are also presented in Table 5 . In the univariate analysis, 6B/6B.1/6B.2 season, age (50-64 years), onset to presentation, underlying conditions, obesity, smoking, alcoholism, and antiviral therapy were significant risk factors of complications, pneumonia, mechanical ventilation, and ARDS (Tables 4 and 5 ). In the multivariate logistic regression analysis, 6B/6B.1/6B.2 season, age (50-64 years and ≥65 years), underlying conditions, and antiviral therapy were significant independent risk factors of complications, pneumonia, and mechanical ventilation (Tables 4 and 5).
cord-331244-zaguyxm5	2004	
cord-331714-2qj2rrgd	2015	Among them are viruses associated with sporadic cases or outbreaks of human disease, such as hemorrhagic fever with renal syndrome (viruses of the genus Hantavirus), Crimean–Congo hemorrhagic fever (CCHFV, Nairovirus), California encephalitis (INKV, TAHV, and KHATV; Orthobunyavirus), sandfly fever (SFCV and SFNV, Phlebovirus), Tick-borne encephalitis (TBEV, Flavivirus), Omsk hemorrhagic fever (OHFV, Flavivirus), West Nile fever (WNV, Flavivirus), Sindbis fever (SINV, Alphavirus) Chikungunya fever (CHIKV, Alphavirus) and others. Artashat virus (ARTSV, strain LEIV-2236Ar) was originally isolated from Ornithodoros alactagalis ticks (family Argasidae) collected in the burrows of a small five-toed jerboa (Allactaga elater) near Arevashat village (40 02 absence of antigenic relationships with any known viruses, it was referred to as an "unclassified bunyavirus." 1À3 Taxonomy.
cord-332485-8tfgl8rp	2002	
cord-332516-eaqpiq1o	2013	
cord-333527-66dfphxq	2010	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. 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 (H5N1), seasonal influenza, and the common cold. 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 (H5N1), seasonal influenza, and the common cold.
cord-333722-ndth5zne	2015	
cord-334424-z7ygy25e	2012	
cord-335647-dhcxj7cj	2013	We here focus on emerging options to interfere with the influenza virus entry process, which consists of the following steps: attachment of the viral hemagglutinin to the sialylated host cell receptors, endocytosis, M2‐mediated uncoating, low pH‐induced membrane fusion, and, finally, import of the viral ribonucleoprotein into the nucleus. There are three conceivable strategies for inhibiting attachment of influenza virus to its target cell: (i) an antiviral compound binding to the HA RBS; (ii) an inhibitor blocking the sialic acid-containing receptors on the epithelial cell membrane; or (iii) a receptor-destroying agent. 91 Regarding potential antiviral use, design of modified forms of the porcine SP-D lectin (which has higher anti-influenza virus activity than its human counterpart) is aided by the growing insight into how its carbohydrate recognition domain (CRD) precisely interacts with the high-mannose glycans attached near the RBS of HA.
cord-335948-qkfxfmxb	2011	
cord-335960-biwnqa3f	2007	
cord-336168-hvp13ell	2009	
cord-336465-qrok21qo	2013	The evaluation of specificity and sensitivity was conducted on stored nasal swab samples collected from emergency department patients presenting with influenza-like symptoms at a large military academic hospital and on de-identified nasal swabs and isolated RNA from a local epidemiology laboratory. Fourteen of the 20 ED samples, plus the 3 samples from the epidemiology laboratory with no virus detected, and the 5 Streptococcus pyogenes bacterial samples were used as the 22 negative controls for both the influenza A and influenza B calculations (see Table 1 A total of 3 false-positive (positive by the Lucigen system but negative by the gold standard Luminex RVP assay) influenza A and 6 false-positive influenza B results were observed with the PyroScript influenza tests. The novel influenza A H1(sw)N1 RNA sample not detected by this microarray technique was also reevaluated by the Luminex RVP assay, and no viral etiology could be identified.
cord-336493-ggo9wsrm	2013	In our present study, we investigated the clinical characteristics and immune cross-reactivity of significant H1N1 influenza strains in the past 100 years in ferrets to determine the immunogenicity of important H1N1 viruses. Ferrets show respiratory illness similar to humans and clinical features of disease are easily observed where fevers can persist days following infection of viruses such as 2009 H1N1pdm influenza 21, 23, 30 . As well as fever, nasal discharge and sneezing can also be observed in animals infected with influenza viruses 21 These influenza A viruses were chosen due to their emergence and influence in H1N1 genetic history (Fig. 1 , strains used in this study are marked with an asterisks) as covered in the introduction. The immunogenic findings showed antisera produced from ferret infection with Taiwan/86 was not able to inhibit hemagglutination with the other viruses on our virus panel, which compliments the literature describing the 1986 strain.
cord-336915-dbu93ufh	2012	We report the case of a young postpartum woman, who developed evidence of respiratory failure reaching the point of requiring intubation due to an H1N1 influenza virus infection two days after a caesarean delivery. We emphasize the diagnosis, management, and the outcome focusing on the question "what the care providers, including obstetric health care workers, ought to know?" Diagnostic and management strategy for pregnant or postpartum women with novel influenza A (H1N1) viral infection and increased awareness amongst patients and health care professionals may result in improved survival. A reported systematic literature review found that pregnancy was associated with increased risk of hospital and intensive care unit (ICU) admission and death, while pregnant women who received delayed treatment with neuraminidase inhibitors or who had additional risk factors were more likely to develop severe disease and preterm births [2] .
cord-337721-who0xdyz	2019	
cord-338674-tnnd1s57	2011	
cord-339230-cc7gcy5b	2014	Several different animal models have been used to study the effect that influenza viruses have on bacterial transmission and colonization and on invasive diseases, such as acute otitis media and pneumonia (Wherry and Butterfield 1921; Shope 1931; Francis and de Torregrosa 1945; Berendt et al. Although the precise mechanisms responsible for enhancing the transmission profile that influenza viruses provide pneumococci are currently unknown, it is likely due to an increase in pathogen density and frequency of secretion events (e.g., sneezing and coughing) in the infected individual combined with a decrease in immunity and resistance from natural barriers breaking down in the person who is newly exposed. The PB1-F2 protein of some influenza viruses increases pathologic effects by causing cell death, increasing viral replication, and altering inflammatory responses to primary viral infections and to bacterial coinfections (Conenello et al.
cord-339638-yrxoj1hl	2020	
cord-340611-7ftnttm0	2004	
cord-340678-2e2s1gof	2020	Influenza vaccine effectiveness against influenza and non-influenza respiratory viruses (NIRV) was assessed by test-negative design using historic datasets of the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN), spanning 2010-11 to 2016-17. Here, we use historic datasets of the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) to assess the association between influenza vaccine and NIRV risk, notably seasonal coronaviruses. Conversely, influenza vaccine had no effect on non-influenza causes of ILI, with the likelihood of vaccination among NIRV cases relative to test-negative controls approaching unity. In combined NIRV analysis, relative to pan-negative controls, Wolff adjusted for age and excluded specimens that tested influenza-positive. We illustrate the impact of this bias in Supplementary_Material_3, where we have re-analyzed Wolff''s data as well as our own, comparing influenza vaccine effect against NIRV when influenza testpositive specimens are properly excluded (as per TND prerequisite) or improperly included (as per Wolff [4] ) within the control group.
cord-341364-dle938bt	2009	
cord-341626-04svm6le	2009	For the Netherlands, we estimated age and risk-group specific numbers of antibiotics, otologicals and cardiovascular prescriptions per 10,000 person-years during periods with elevated activity of influenza or RSV, and compared these with peri-season rates. The exact age of any person was determined every year on the 1st of October, close to the period in which in the Netherlands the invitations for influenza vaccination for risk groups are sent out by the GPs, supposedly just prior to the season with increased risk for influenza epidemics from October onwards to May. The annual total population sizes were based on estimates for the 1st of January by the local authorities in the places where the pharmacies are located. In addition, more than average numbers of antibiotics may be prescribed for elderly persons with ILI during periods with elevated activity, as particularly this group may develop acute respiratory illnesses (for example, pneumonia) as a complication of the viral infection (trimethoprim and nitrofurantoin were excluded from the analysis as they are prescribed primarily for urinary tract infections) [33] .
cord-341923-jwckbdnb	2010	
cord-342519-tjr6dvtt	2010	
cord-342796-f7n8sxbu	2020	
cord-343050-1pfqgvie	2015	
cord-345020-ai5tib7h	2019	Studies investigating viral interference since the pandemic are sparser, though two studies reported that the timing and magnitude of respiratory virus epidemics were affected by the timing of the seasonal influenza A peak [15, 16] . We used routine diagnostic testing data of specimens from both the community and hospitals at the Victorian Infectious Diseases Reference Laboratory (VIDRL) between 2002 and 2017 to describe relationships between respiratory viruses, with a focus on influenza A and RSV. Seasonality of viruses was assessed visually by time series analysis and for further investigation each virus was compared with influenza A and RSV using cross-correlations that estimated the association between peaks in epidemic curves at a lag or lead of up to 15 weeks. Results of further investigation by logistic regression adjusted for covariates that are predictors of codetection (sex, age and season) were compatible with influenza A, RSV and picornavirus conferring temporary immunity against infection by another respiratory virus.
cord-345836-74d2mb70	2007	
cord-345848-s84lxe6l	2012	We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. We find that a statistically significant number of hospitalised subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Given the higher viral load in Ifitm3 −/− mice and increased replication of influenza A virus in Ifitm3 deleted cells in vitro (Fig. 1d) , we examined both viral nucleic acid and protein distribution in the lung. Analysis of cell populations resident in the lung tissue on day 6 post-infection showed that Ifitm3 −/− mice displayed significantly reduced proportions of CD4+ (p=0.004) and CD8+ Tcells (p=0.02) and natural killer (NK) cells (p=0.0001) but an elevated proportion of neutrophils (p=0.007) (Fig. 3a) .
cord-346063-7u1a198p	2007	We have recently reviewed the antiviral agents that are active against influenza viruses and that could be used, either therapeutically and/or prophylactically, in an influenza virus pandemic, whether it be human, avian, equine, porcine or other [1] . Even if based only on the currently available drugs, there are several double-, tripleand quadruple-drug combinations that could be envisaged for the prevention and treatment of avian H5N1 (Figure 3 ) -including the combination of oseltamivir and zanamivir (because their resistance profiles overlap only partially), the combination of these neuraminidase inhibitors with M2 ion channel blockers, and further extension of these combinations to include pegylated interferon and ribavirin. In addition to viral RNA polymerase and/or endonuclease, mentioned earlier as potential targets for new anti-influenza-virus agents, there are some other clues regarding the virulence of H5N1 viruses in humans [41] that could be considered as points of attack for chemotherapeutic intervention.
cord-346906-1wmp43ti	2019	We determine its sensitivity compared to that of existing diagnostic methods and its accuracy compared to short-read (Illumina) sequencing, using clinical samples from hospital patients during an influenza season and samples from a controlled laboratory infection in ferrets. During the study, respiratory samples submitted to the clinical diagnostic laboratory were routinely tested by a PCR-based test using the GeneXpert assay (Cepheid) to detect influenza A and B viruses and respiratory syncytial virus (RSV). Comparing this final method with our original protocol, using triplicate extractions from the pooled set of influenza A virus-positive samples demonstrated no significant loss in performance in the more rapid protocol (Fig. S3) , and we adopted this approach as our routine protocol, giving a wet-lab processing time of ϳ8 h. Future application of this method will involve real-time laboratory testing of respiratory samples, running the platform head to head with existing clinical diagnostics to further assess sensitivity and specificity, and using influenza virus sequence data to investigate transmission events.
cord-350593-bvmg7f15	2012	
cord-351990-aham72b9	2014	
cord-352984-mzv9t7ex	2016	title: Mandating influenza vaccinations for health care workers: analysing opportunities for policy change using Kingdon''s agenda setting framework In the case of mandatory influenza vaccinations for HCWs in Ontario, it seems highly unlikely that a new policy will be adopted until perception of the problem''s importance is sufficient to overcome the political opposition to implementing a solution and thus, create a window of opportunity that is open long enough to support change. Using Kingdon''s agenda setting framework (three process streams that lead to windows of opportunity when they converge) the objective of this paper is to analyse the likelihood of government adopting a mandatory vaccination policy for HCWs in Ontario. Despite broad public acceptance and substantial participation in the voluntary immunization program, pockets of HCW resistance persisted (politics stream), and outbreaks in long-term care facilities and hospitals continued to occur, resulting in preventable illness and death [23] .
cord-353869-l53ms3q8	2010	METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza. Mean decline in body weight at the end of the experiment was 6.2% in the group of ferrets that received CR6261 4 hours after challenge ( Figure 2B) , which was significantly less (p = 0.025) than the 10.1% observed in control animals. These findings were in accordance with the observation that the mean lung weights of ferrets treated with CR6261 at 4 hours post challenge were lower compared to the control group (5.7 g versus 14.9 g, p,0.001; Figure 2F ).
cord-353871-mzw600ys	2017	Infections in every epidemic season induced by respiratory viruses, especially by the influenza virus, are the cause of many illnesses and complications which often end in death. The aim of the present study was to analyze the activity influenza and influenza-like viruses in people over the age of 14 in the 2015/2016 influenza season in Poland, according to the new reporting system (Bednarska et al. Interestingly, the number of confirmed cases of influenza virus was the highest in the same age-groups of 45-64 and 26-44 years in the past 2013/2014 season (Bednarska et al. An increased number of confirmed cases of infection in the currently evaluated season was mainly caused by the influenza virus and to a lesser extent by influenza-like viruses, which may lead to a severer disease course, complications, and in consequence to death.
cord-354151-psog34u3	2015	
cord-354690-ywb9krdp	2008	Most of the existing information about a population''s response to the threat of pandemics comes from research on outbreaks of the SARS coronavirus, most notably in Hong Kong, Singapore, and Canada, [2] [3] [4] [5] and on studies of risk perception and anticipated behaviours in a potential pandemic in humans from the avian influenza virus (especially the H5N1 subtype). For the hypothetical questions -that is, likelihood of pandemic influenza, likelihood that family or self affected, willingness to comply with vaccination, isolation or wearing a face mask -the responses of extremely likely and very likely were combined into the indicator of interest. Table 4 shows the indicators for pandemic influenza likely, concern for self and family, and changed life by sex, age group, demographic characteristics, and the indicators of level of psychological distress and general self-rated health status.
cord-354877-n5du3bqt	2009	
cord-355374-e8k72955	2018	Influenza virus-specific CD8 + Trm in human lung tissue also maintain diverse TCR profiles-a feature important for effective T cell function and protection against the generation of viral-escape mutants [128] . HLA-I allele expression is an important predictor of cross-reactive influenza-specific CD8 + T cell immunity, with a recent study identifying five alleles (A*02:01, A*03:01, B*57:01, B*18:01, and B*08:01) capable of eliciting robust CD8 + T cell responses against immunogenic NP and M1 peptides that are conserved across all human influenza A virus, including the novel avian-derived H7N9 virus [18] . Thus, upon infection with H7N9, individuals with these HLA alleles will need time to activate and amplify new primary CD8 + T cell responses to distinct H7N9 peptide variants rather than recalling T cell responses generated against seasonal influenza viruses, potentially resulting in longer time to recovery and greater risk of severe disease compared to individuals with pre-existing cross-protective CD8 + T cell memory.
cord-356188-rwf78stz	2012	Few studies have examined the role of monocytes during influenza infection in humans, particularly regarding the specific subsets mentioned above, but comparison of IFN-␥ production from T cells cocultured with CD64 ϩ CD16 Ϫ and CD64 Ϫ CD16 ϩ monocytes [119, 120] Cellular immunity Class I HLA presents peptides from internal and external viral proteins. As influenza primarily infects epithelial cells lining the respiratory tract, lung-resident DCs and macrophages are particularly important for efficient development of an adaptive immune response. [189] ), and in vitro studies suggest that activated human V␥9V␦2 T cells may have a role in the antiviral response by killing influenza-infected, monocyte-derived macrophages and producing high levels of IFN-␥ [190, 191] . Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection Characterization of the human CD8ϩ T cell response following infection with 2009 pandemic influenza H1N1 virus