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    The impact of obesity and timely antiviral administration on severe influenza outcomes among hospitalized adults. Segaloff Hannah E,Evans Richard,Arshad Samia,Zervos Marcus J,Archer Carolyn,Kaye Keith S,Martin Emily T Journal of medical virology Obesity was identified as a risk factor for severe influenza during the 2009 influenza A(H1N1)pandemic, but evidence of this association has been mixed since. Post-pandemic antiviral treatment guidelines may have increased antiviral treatment among obese individuals. A prospective study of adults hospitalized with laboratory-confirmed influenza in Detroit, Michigan in 2011-2012 and 2012-2013 was conducted. Patient information was collected from interviews and medical chart abstraction. Obese (BMI ≥ 30) and non-obese (BMI < 30) participants were compared. Late antiviral treatment (>2 days from symptom onset), obesity (30 ≤ BMI < 40), and morbid obesity (BMI ≥ 40) were evaluated as predictors of lower respiratory tract disease (LRD), ICU admission, and length of stay (LOS) using logistic regression and inverse probability weighted models. Forty-eight participants were included in the study after exclusions and all patients received antiviral treatment. Participants who were obese were significantly more likely to have a cough and to take steroids than non-obese participants, and had a shorter time from hospital admission to antiviral treatment (median time from admission to treatment of 0 days for obese patients and 1 day for non-obese patients [P = 0.001]). In all models, late antiviral treatment was associated with increased odds of LRD (OR: 3.9 [1.1,15.9] in fully adjusted model). After adjustment for treatment timing, the odds of ICU admission (OR: 6.4 [0.8,58.2] to 7.9 [0.9, 87.1]) and LRD (OR: 3.3 [0.5, 23.5] to 4.0 [0.6, 35.0]) associated with morbid obesity increased. Obese individuals were treated with antivirals earlier than others. Late antiviral treatment was associated with severe influenza in the hospital. 10.1002/jmv.24946
    [Estimation of the population attributable fraction due to obesity in hospital admissions for flu valued according to Body Mass Index (BMI) and CUN-BAE]. Dávila-Batista V,Carriedo D,Díez F,Pueyo Bastida A,Martínez Durán B,Martin V, Semergen INTRODUCTION:The obesity pandemic together with the influenza pandemic could lead to a significant burden of disease. The body mass index (BMI) does not discriminate obesity appropriately. The CUN-BAE has recently been used as an estimate of body fatness for Caucasians, including BMI, gender, and age. The aim of this study is to assess the population attributable fraction of hospital admissions due to influenza, due to the body fatness measured with the BMI, and the CUN-BAE. METHODS:A multicentre study was conducted using matched case-controls. Cases were hospital admissions with the influenza confirmed by the RT-PCR method between 2009 and 2011. The risk of hospital admission and the population attribuible fraction were calculated using the BMI or the CUN-BAE for each adiposity category in a conditional logical regression analysis adjusted for confounding variables. The analyzes were estimated in the total sample, in unvaccinated people, and those less than 65 years-old. RESULTS:A total of 472 hospitalised cases and 493 controls were included in the study. Compared to normal weight, the aOR of influenza hospital admissions increases with each level of BMI (aOR=1.26; 2.06 and 11.64) and CUN-BAE (aOR=2.78; 4.29; 5.43 and 15.18). The population attributable fraction of influenza admissions using CUN-BAE is 3 times higher than that estimated with BMI (0,72 vs. 0,27), with the differences found being similar the non-vaccinated and under 65 year-olds. CONCLUSION:The BMI could be underestimating the burden of disease attributable to obesity in individuals hospitalised with influenza. There needs to be an appropriate assessment of the impact of obesity and vaccine recommendation criteria. 10.1016/j.semerg.2017.01.011
    Body mass index and the incidence of influenza-associated pneumonia in a UK primary care cohort. Blumentals William A,Nevitt Alan,Peng Michael M,Toovey Stephen Influenza and other respiratory viruses BACKGROUND:Accumulating data suggest an association between increased BMI/obesity and morbidity in patients with pandemic (H1N1) 2009 influenza. Information on metabolic status and prognosis in seasonal influenza is lacking, however. METHODS:A retrospective cohort study was carried out using the UK General Practice Research Database. Patients aged ≥18 with ≥1 recorded BMI in the 12-58 kg/m(2) range between January 1, 2000, and December 31, 2007, were observed for an influenza-associated pneumonia diagnosis after the date of baseline BMI, including 'influenza with pneumonia' or a diagnosis of 'pneumonia' up to 30 days after a diagnosis of 'influenza'. RESULTS:A total of 1,074,315 patients were included, of whom 73·2% were within the reference BMI range or overweight and 2·2% were underweight (<18·5 kg/m(2)). Pneumonia rates were 32·33-37·48/100,000 in all BMI categories except the underweight (98·29/100,000). Relative to patients with acceptable weight, those who were underweight had an increased pneumonia rate [adjusted IRR = 2·32 (95% CI 1·80-2·94)], while being overweight (BMI = 25·0-29·9 kg/m(2)) or obese (BMI ≥ 30·0 kg/m(2)) was associated with a decreased pneumonia rate [adjusted IRR = 0·77 (95% CI 0·68-0·86) and 0·85 (95% CI 0·73-1·00), respectively]. On the other hand, women and obese women with type 2 diabetes had increased pneumonia rates [adjusted IRR = 1·37 (95% CI 1·08-1·72) and 1·47 (95%CI 1·01-2·06), respectively]. CONCLUSIONS:In contrast to initial data from pandemic influenza, influenza pneumonia, and pneumonia following influenza were the most common in underweight persons, and an apparent decreased rate of pneumonia was noted with increasing BMI categories. Women with type 2 diabetes had increased rates of pneumonia. 10.1111/j.1750-2659.2011.00262.x
    Influenza in obese travellers: increased risk and complications, decreased vaccine effectiveness. Honce Rebekah,Schultz-Cherry Stacey Journal of travel medicine BACKGROUND:Obesity is a worldwide epidemic and was empirically shown to increase the risk of developing severe influenza virus infection. As international travel becomes more common and obesity is now prevalent even in low- and middle-income countries, travellers may have an increased risk of contracting influenza virus especially during peak influenza season. METHODS:An analysis of the literature, centred on publications from 2014-19, was performed, with an emphasis on human epidemiological data, human studies ex vivo and studies in mouse models of obesity. Our search efforts focused on influenza disease severity, pathogenesis, evolutionary dynamics and measures of infection control in the obese and overweight host. RESULTS:Obesity is associated with an increased risk of infection, as well as a greater chance for hospitalization and severe complications. Studies in mouse models of obesity have uncovered that obese hosts suffer increased viral spread, delayed viral clearance and heightened damage to the respiratory epithelium. Innate and adaptive immune responses are delayed, thus increasing morbidity and mortality. Further, infection control measures, including vaccination and antivirals, prove less effective in obese hosts. Finally, the obese microenvironment allows for increased duration and amount of viral shedding and potentially increases the chance for emergence of virulent minor variants in the viral population. Together, obese hosts are at high risk of influenza infection, as well as severe sequelae following infection. CONCLUSION:Obese travellers should be aware of influenza activity in the regions visited, as well as take protective measures prior to travel. Vaccination is highly recommended for all travellers, but especially highly susceptible obese travellers. 10.1093/jtm/taz020
    Immunogenicity, safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children. Esposito Susanna,Giavoli Claudia,Trombetta Claudia,Bianchini Sonia,Montinaro Valentina,Spada Anna,Montomoli Emanuele,Principi Nicola Vaccine Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p<0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p<0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p<0.01 for GMT values and p<0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile. 10.1016/j.vaccine.2015.11.019
    The impact of obesity on the immune response to infection. Milner J Justin,Beck Melinda A The Proceedings of the Nutrition Society There is strong evidence indicating that excess adiposity negatively impacts immune function and host defence in obese individuals. This is a review of research findings concerning the impact of obesity on the immune response to infection, including a discussion of possible mechanisms. Obesity is characterised by a state of low-grade, chronic inflammation in addition to disturbed levels of circulating nutrients and metabolic hormones. The impact of these metabolic abnormalities on obesity-related comorbidities has undergone intense scrutiny over the past decade. However, relatively little is known of how the immune system and host defence are influenced by the pro-inflammatory and excess energy milieu of the obese. Epidemiological data suggest obese human subjects are at greater risk for nosocomial infections, especially following surgery. Additionally, the significance of altered immunity in obese human subjects is emphasised by recent studies reporting obesity to be an independent risk factor for increased morbidity and mortality following infection with the 2009 pandemic influenza A (H1N1) virus. Rodent models offer important insight into how metabolic abnormalities associated with excess body weight can impair immunity. However, more research is necessary to understand the specific aspects of immunity that are impaired and what factors are contributing to reduced immunocompetence in the obese. Additionally, special consideration of how infection in this at-risk population is managed is required, given that this population may not respond optimally to antimicrobial drugs and vaccination. Obesity impacts millions globally, and greater understanding of its associated physiological disturbances is a key public health concern. 10.1017/S0029665112000158
    Clinical features, risk factors, and complications among pediatric patients with pandemic influenza A (H1N1). Plessa Eleni,Diakakis Panagiotis,Gardelis John,Thirios Athanasios,Koletsi Patra,Falagas Matthew E Clinical pediatrics OBJECTIVE:The authors aimed to describe the epidemiological characteristics, clinical features, risk factors for severe disease, and complications in children with laboratory-confirmed pandemic influenza A (H1N1). METHODS:H1N1 was confirmed by performing reverse-transcriptase polymerase chain reaction (RT-PCR) assay on oropharyngeal swab specimens. The medical charts of a subset of the evaluated patients were reviewed retrospectively; another subset was enrolled prospectively. RESULTS:A total of 51 patients (44 [86%] > 5 years) were identified to have laboratory-confirmed H1N1. Fever was the most common presenting symptom (92%). Of the 15 hospitalized patients, 4 had asthma, and 5 were overweight or obese. All but 1 of these 9 patients developed influenza-related complications. Overall, 10 of the 15 hospitalized patients (67%) developed an influenza-related complication (6 bronchitis and 4 pneumonia). CONCLUSION:In this cohort, most children with confirmed H1N1 infection experience an uncomplicated viral illness. Nevertheless, underlying asthma and obesity may aggravate their clinical course. 10.1177/0009922810368558
    [Body adiposity: An undervalued risk factor in hospital admission due to influenza]. Gómez-Ambrosi J Semergen 10.1016/j.semerg.2018.02.008
    Adiposity and influenza-associated respiratory mortality: a cohort study. Zhou Ying,Cowling Benjamin J,Wu Peng,Chan Wai Man,Lee Siu Yin,Lau Eric H Y,Schooling C Mary Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:Obesity was first noted as a risk factor for severe illness associated with pandemic H1N1 infection in 2009, but the relationship between obesity and seasonal influenza remains unclear. METHODS:We used data from a population-based cohort comprising 66 820 older (≥65 years) participants with a follow-up period from 1998 to 2012. The impact of influenza activity on respiratory mortality rates was estimated using a Cox proportional hazards model adjusted for comorbidities, meteorological factors, and other co-circulating respiratory viruses. We also tested whether the association of influenza with respiratory mortality varied with obesity and/or health status. As a control outcome, we similarly assessed the association of influenza with deaths from external causes, because these deaths should be unrelated to influenza. RESULTS:Seasonal influenza activity was associated with higher respiratory mortality (hazard ratio [HR], 1.13 for influenza activity in the influenza season vs noninfluenza season; 95% confidence interval [CI], 1.05-1.22). The effect of seasonal influenza was 19% greater in obese individuals than normal-weight individuals (HR, 1.19; 95% CI, 1.01-1.42). The marginally significant and greater effect modification of obesity status on the association between seasonal influenza and respiratory mortality was also observed among older people in good health (HR, 1.35; 95% CI, .97-1.87). No such relations were observed for death from external causes. CONCLUSIONS:Obesity aggravates the effect of seasonal influenza on respiratory mortality. Priority for influenza vaccine should be considered for obese older people to decrease the burden of influenza. 10.1093/cid/civ060
    Immune response in highly active young men to the 2014/2015 seasonal influenza vaccine. Stewart Andrew,Vanderkooi Otto G,Reimer Raylene A,Doyle-Baker Patricia K Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme During the 2009 H1N1 pandemic, individuals with obesity were disproportionately affected by H1N1 with increased levels of mortality and morbidity. This led to questions regarding the potential impact of lifestyle on the effectiveness of immunization. Currently, the research is limited on influenza vaccination and the associated changes in immune response with body composition and physical activity. The purpose of this pilot study was to investigate the potential role of adiposity and physical activity in the immune response elicited by the 2014/2015 seasonal trivalent influenza vaccine. A prospective cohort study examining the 2014/2015 seasonal trivalent influenza vaccine was conducted by collecting baseline and 4-week postvaccination fasting blood samples from 45 male Albertans between the ages of 18 and 35 years. Percent body fat (%BF) was assessed through dual X-ray absorptiometry imagining and physical activity through self-reported survey scores. While no differences in median %BF were associated with seroconversion rates in participants, the median physical activity score was higher among those that did not seroconvert to the vaccine. Significant differences were found for the A/Texas strain (p < 0.01) and a similar trend of lower magnitude observed for the remaining 2 influenza strains. These results suggest that higher physical activity levels may influence immune response to vaccination and that assessing factors beyond those commonly used can be of value when identifying vaccine response in the population. 10.1139/apnm-2017-0683
    Interaction of obesity and infections. Dhurandhar N V,Bailey D,Thomas D Obesity reviews : an official journal of the International Association for the Study of Obesity There is evidence that certain infections may induce obesity. Obese persons may also have more severe infections and have compromised response to therapies. The objective of this study is to review the available literature identifying infections that potentially contribute to greater body mass index (BMI) and differential responses of overweight and obese persons to infections. A systematic literature review of human studies examining associations between infections and weight gain, differential susceptibility, severity, and response to prevention and treatment of infection according to BMI status (January 1980-July 2014) was conducted. Three hundred and forty-three studies were eligible for inclusion. Evidence indicated that viral infection by human adenovirus Ad36 and antibiotic eradication of Helicobacter pylori were followed by weight gain. People who were overweight or obese had higher susceptibility to developing post-surgical infections, H1N1 influenza and periodontal disease. More severe infections tended to be present in people with a larger BMI. People with a higher BMI had a reduced response to vaccinations and antimicrobial drugs. Higher doses of antibiotics were more effective in obese patients. Infections may influence BMI, and BMI status may influence response to certain infections, as well as to preventive and treatment measures. These observations have potential clinical implications. 10.1111/obr.12320
    A Perfect Storm: Increased Colonization and Failure of Vaccination Leads to Severe Secondary Bacterial Infection in Influenza Virus-Infected Obese Mice. Karlsson Erik A,Meliopoulos Victoria A,van de Velde Nicholas C,van de Velde Lee-Ann,Mann Beth,Gao Geli,Rosch Jason,Tuomanen Elaine,McCullers Jon,Vogel Peter,Schultz-Cherry Stacey mBio Obesity is a risk factor for developing severe disease following influenza virus infection; however, the comorbidity of obesity and secondary bacterial infection, a serious complication of influenza virus infections, is unknown. To fill this gap in knowledge, lean and obese C57BL/6 mice were infected with a nonlethal dose of influenza virus followed by a nonlethal dose of Strikingly, not only did significantly enhanced death occur in obese coinfected mice compared to lean controls, but also high mortality was seen irrespective of influenza virus strain, bacterial strain, or timing of coinfection. This result was unexpected, given that most influenza virus strains, especially seasonal human A and B viruses, are nonlethal in this model. Both viral and bacterial titers were increased in the upper respiratory tract and lungs of obese animals as early as days 1 and 2 post-bacterial infection, leading to a significant decrease in lung function. This increased bacterial load correlated with extensive cellular damage and upregulation of platelet-activating factor receptor, a host receptor central to pneumococcal invasion. Importantly, while vaccination of obese mice against either influenza virus or pneumococcus failed to confer protection, antibiotic treatment was able to resolve secondary bacterial infection-associated mortality. Overall, secondary bacterial pneumonia could be a widespread, unaddressed public health problem in an increasingly obese population. Worldwide obesity rates have continued to increase. Obesity is associated with increased severity of influenza virus infection; however, very little is known about respiratory coinfections in this expanding, high-risk population. Our studies utilized a coinfection model to show that obesity increases mortality from secondary bacterial infection following influenza virus challenge through a "perfect storm" of host factors that lead to excessive viral and bacterial outgrowth. In addition, we found that vaccination of obese mice against either virus or bacteria failed to confer protection against coinfection, but antibiotic treatment did alleviate mortality. Combined, these results represent an understudied and imminent public health concern in a weighty portion of the global population. 10.1128/mBio.00889-17
    Impact of Obesity on Influenza A Virus Pathogenesis, Immune Response, and Evolution. Honce Rebekah,Schultz-Cherry Stacey Frontiers in immunology With the rising prevalence of obesity has come an increasing awareness of its impact on communicable disease. As a consequence of the 2009 H1N1 influenza A virus pandemic, obesity was identified for the first time as a risk factor for increased disease severity and mortality in infected individuals. Over-nutrition that results in obesity causes a chronic state of meta-inflammation with systemic implications for immunity. Obese hosts exhibit delayed and blunted antiviral responses to influenza virus infection, and they experience poor recovery from the disease. Furthermore, the efficacy of antivirals and vaccines is reduced in this population and obesity may also play a role in altering the viral life cycle, thus complementing the already weakened immune response and leading to severe pathogenesis. Case studies and basic research in human cohorts and animal models have highlighted the prolonged viral shed in the obese host, as well as a microenvironment that permits the emergence of virulent minor variants. This review focuses on influenza A virus pathogenesis in the obese host, and on the impact of obesity on the antiviral response, viral shed, and viral evolution. We comprehensively analyze the recent literature on how and why viral pathogenesis is altered in the obese host along with the impact of the altered host and pathogenic state on viral evolutionary dynamics in multiple models. Finally, we summarized the effectiveness of current vaccines and antivirals in this populations and the questions that remain to be answered. If current trends continue, nearly 50% of the worldwide population is projected to be obese by 2050. This population will have a growing impact on both non-communicable and communicable diseases and may affect global evolutionary trends of influenza virus. 10.3389/fimmu.2019.01071
    Obesity decreases B cell responses in young and elderly individuals. Frasca Daniela,Ferracci Franco,Diaz Alain,Romero Maria,Lechner Suzanne,Blomberg Bonnie B Obesity (Silver Spring, Md.) OBJECTIVE:To evaluate the effects of obesity-associated inflammation on influenza vaccine responses. METHODS:In young and elderly individuals, both lean and with obesity, antibody responses to influenza vaccination were measured. RESULTS:A decrease in in vivo vaccine responses, circulating switched memory, and transitional B cells and an increase in pro-inflammatory late/exhausted memory B cells were found. In vitro B cell function was measured by activation-induced cytidine deaminase and E47, markers of optimal antibody responses. Moreover, IL-6 production was increased, whereas IL-10 production was decreased in cultures of B cells from individuals with obesity. Markers of immune activation (TNF-α, TLR4, micro-RNAs) in unstimulated B cells were also found increased and were negatively correlated with B cell function. In order to reveal potential mechanisms, we stimulated B cells from lean individuals in vitro with leptin, the adipokine increased in obesity. Leptin increased phospho-STAT3, crucial for TNF-α production, and decreased phospho-AMPK, the energy sensing enzyme upstream of phospho-p38 MAPK and E47. Leptin-induced phospho-STAT3 and phospho-AMPK levels were similar to those in B cells from individuals with obesity. CONCLUSIONS:These results demonstrate that leptin can be responsible for decreased B cell function in obesity. 10.1002/oby.21383
    Dose-response relationship between weight status and clinical outcomes in pediatric influenza-related respiratory infections. Okubo Yusuke,Michihata Nobuaki,Uda Kazuhiro,Morisaki Naho,Miyairi Isao,Matsui Hiroki,Fushimi Kiyohide,Yasunaga Hideo Pediatric pulmonology BACKGROUND:Associations between underweight/obesity and manifestations of influenza infection remain unclear, especially in children. This study investigated the dose-response relationships between weight status and clinical outcomes among children hospitalized with influenza-related respiratory infections. METHODS:We obtained hospital discharge records of inpatients aged under 18 years with diagnoses of bronchitis/pneumonia and influenza, using a Japanese national inpatient database. The patients were classified as underweight, normal-weight, overweight, or obese groups using weight-for-length, weight-for-height, and body-mass-index for age following World Health Organization criteria. We compared need for intensive care, 30-day readmission, mean total hospitalization costs, and length of hospital stay across the four groups using multivariable regression models and restricted cubic spline functions. RESULTS:Overall, 27 771 patients were identified, including 2637 underweight, 19 701 normal-weight, 2675 overweight, and 2758 obese patients. The underweight group showed a significantly higher 30-day readmission (adjusted odds ratio, 1.68; 95% confidence interval, 1.28-2.18) and a longer length of stay (adjusted difference, 0.23 days; 95% confidence interval, 0.12-0.23 days) than the normal-weight group did. No significant differences in the need for intensive care or hospitalization costs were observed across the four weight status groups. The threshold for a statistically significant association between weight status and 30-day readmission was a z-score for weight-for-length, weight-for-height, or BMI for age of -0.95 (17th percentile). CONCLUSION:These findings demonstrated that underweight status is a risk factor for repeated hospital admissions because of influenza-related respiratory infections in children. 10.1002/ppul.23927
    Influenza Vaccine is Protective Against Laboratory-confirmed Influenza in Obese Children. Smit Michael A,Wang Hai-Lin,Kim Edward,Barragan Noel,Aldrovandi Grace M,El Amin Alvin Nelson,Mascola Laurene,Pannaraj Pia S The Pediatric infectious disease journal BACKGROUND:Obesity emerged as a novel risk factor for severe disease during the 2009 H1N1 influenza pandemic. Murine studies indicate that obesity is associated with ineffective response to influenza vaccine, but few human studies exist. We aimed to determine if influenza vaccine is protective against laboratory-confirmed influenza in obese children. METHODS:Body mass index, vaccination status, and laboratory-confirmed influenza data were analyzed from a previously conducted prospective study in which active surveillance for influenza-like illness was conducted in 8 elementary schools in Los Angeles County during the 2010-2011 influenza season. Polymerase-chain reaction (PCR) was performed on combined nose/throat swabs collected from children with influenza-like illness at presentation to the school nurse or during absenteeism. RESULTS:Of 4260 children with height/weight data, 1191 (28.0%) were obese (body mass index ≥95th percentile). Respiratory specimens were obtained from 858 (20.1%) children. Unvaccinated obese compared with vaccinated obese children acquired 3 times more PCR-confirmed influenza (62 vs. 17 per 1000 children, P = 0.003) and missed more school days (4.6 vs. 3.2 per 100 school days, P < 0.001) during influenza season. Obese children with PCR-confirmed influenza were more likely to present with cough (86.2 vs. 72.4%, P = 0.030) and missed more school per episode (2.4 vs.1.9 days, P = 0.023) compared with nonobese children. Among vaccinated children, rates of PCR-confirmed influenza were similar in obese and nonobese children (17 vs. 20 per 1000 children, P = 0.77). CONCLUSIONS:Obese children with PCR-confirmed influenza suffered from more cough and missed more school days than their nonobese peers. Influenza vaccination protected obese children against PCR-proven influenza illness. 10.1097/INF.0000000000001029
    Beyond Disease Severity: The Impact of Obesity on Influenza A Virus Shedding. Schultz-Cherry Stacey The Journal of infectious diseases 10.1093/infdis/jiy371
    Review on the impact of pregnancy and obesity on influenza virus infection. Karlsson Erik A,Marcelin Glendie,Webby Richard J,Schultz-Cherry Stacey Influenza and other respiratory viruses A myriad of risk factors have been linked to an increase in the severity of the pandemic H1N1 2009 influenza A virus [A(H1N1)pdm09] including pregnancy and obesity where death rates can be elevated as compared to the general population. The goal of this review is to provide an overview of the influence of pregnancy and obesity on the reported cases of A(H1N1)pdm09 virus infection and of how the concurrent presence of these factors may have an exacerbating effect on infection outcome. Also, the hypothesized immunologic mechanisms that contribute to A(H1N1)pdm09 virus severity during pregnant or obese states are outlined. Identifying the mechanisms underlying the increased disease severity in these populations may result in improved therapeutic approaches and future pandemic preparedness. 10.1111/j.1750-2659.2012.00342.x
    Factors influencing on influenza vaccination and its trends of coverage in patients with diabetes in Korea: A population-based cross-sectional study. Shin Hyun-Young,Chung Jae Ho,Hwang Hee-Jin,Kim Tae Ho Vaccine BACKGROUND:Influenza infection is a contagious disease and annual influenza vaccination is recommended to the patients with chronic diseases. Although diabetes is an indication for influenza vaccination, the global rate of influenza vaccination is insufficient. Therefore, our study aimed to elucidate influenza vaccination statuses among patients with diabetes and the related factors in Korea. METHODS:A total of 32,268 subjects (4,540 with and 27,728 without diabetes) from the Korea National Health and Nutrition Examination Survey III-VI (2005-2015) were included. Socioeconomic factors and health-related factors were analyses for the relation of influenza vaccination by Student's t-test, the chi-squared test and a multivariate logistic regression analysis. RESULTS:The influenza vaccination coverage rates were 50.0% in the diabetes mellitus (DM) group and 38.2% in the non-DM group. The trends in influenza vaccination rates during KNHANES III-VI were not significant in each group (P trend  =  0.24 in the DM group, 0.30 in the non-DM group). Socioeconomic (older age, female sex, higher family income, and medical aid insurance) and health-related factors (lack of risky alcohol consumption, obesity, and recent health check-ups) were associated with influenza vaccination among patients with DM. CONCLUSIONS:The rate of influenza vaccination among patients with diabetes is insufficient in Korea. More efforts are needed to increase the influenza vaccination rates among vulnerable at-risk populations. 10.1016/j.vaccine.2017.11.035
    Association between body mass index and laboratory-confirmed influenza in middle aged and older adults: a prospective cohort study. Karki S,Muscatello D J,Banks E,MacIntyre C R,McIntyre P,Liu B International journal of obesity (2005) BACKGROUND:Studies conducted during the 2009 influenza A (H1N1) pandemic found that obesity increases the risk of severe influenza including hospitalization and death. In this study, we examined the relationship of BMI with having laboratory-confirmed seasonal influenza and influenza-related respiratory hospitalization. METHODS:We linked a cohort of 246,494 adults aged ≥45 years with data on BMI to subsequent laboratory-confirmed influenza notifications and cause-specific hospitalizations from 2006 to 2015. Cox-proportional hazard models were used to estimate the risk of incident laboratory-confirmed influenza and influenza-related respiratory hospitalizations according to BMI, adjusting for age, sex and other covariates. RESULTS:After 1,840,408 person-years of follow-up, 1891 participants had laboratory-confirmed influenza notifications (crude rate 10.3/10,000 person-years) of whom 623 were hospitalized for a respiratory illness. Compared to those with healthy BMI (22.5 to <25.0 kg/m, influenza incidence was respectively 27% (adjusted HR [aHR]: 1.27, 95% CI: 1.10-1.46) and 69% (aHR: 1.69, 1.24-2.29) greater among obese (BMI: 30 to <40 kg/m and very obese adults (40 to <50 kg/m. The equivalent aHRs for hospitalization were 1.57 (95% CI: 1.22-2.01) and 4.81 (95% CI: 3.23-7.17). For every 5-unit BMI increase above 22.5 kg/m, there was a 15% (aHR: 1.15, 95% CI: 1.09-1.22) increase in risk of having a diagnosis of influenza and 42% increase in hospitalization (aHR: 1.42, 95% CI: 1.30-1.60). These trends did not differ between the pandemic year (2009) and other years. CONCLUSIONS:Our results suggest that obese adults have a similar risk of hospitalization for seasonal influenza as adults with cardiovascular disease and diabetes, and should therefore  be equally prioritized for funded interventions such as targeted immunization programs. 10.1038/s41366-018-0029-x
    Association between obesity and vulnerability and serologic response to influenza vaccination in older adults. Talbot H K,Coleman L A,Crimin K,Zhu Y,Rock M T,Meece J,Shay D K,Belongia E A,Griffin M R Vaccine BACKGROUND:Serologic response to influenza vaccination declines with age. Few other host factors are known to be associated with serologic response. Our objective was to determine whether obesity and vulnerability independently predicted serologic response to influenza vaccination. METHODS:Adults ≥ 50 years were recruited during the 2008-2009 influenza season. Subjects provided pre- and post-vaccination sera for measuring antibody titers to 2008-2009 vaccine components. Body mass index (BMI) was calculated as weight (kg)/height (m(2)). Data were collected on vulnerability using the vulnerable elders survey (VES13). Logistic regression evaluated the associations between obesity and vulnerability and the serologic response to vaccination (both seroprotection and seroconversion), adjusting for gender, age, comorbidities, pre-vaccination titer, and site. RESULTS:Mean (± standard deviation) age of 415 study subjects was 65 ± 10 years; 40% were obese. Mean BMI was 29 ± 5.6 kg/m(2); mean VES13 was 1.6 ± 1.8. The proportions of subjects who seroconverted and had seroprotective titers were 40% and 49%, respectively, for A/Brisbane/59 (H1N1); 73% and 80% for A/Brisbane/10 (H3N2); and 34% and 94% for B/Florida. Modified VES-13 (score 0-10, with 10 being most vulnerable) was not associated with seroprotection against H1N1 or H3N2, and VES-13 was directly associated with seroconversion to H1N1 but not H3N2 or B. Obesity (BMI ≥ 30 kg/m(2) vs. BMI 18.5-30 kg/m(2)) was not associated with seroprotection for H1N1 or H3N2; obesity was directly associated with seroconversion to H3N2 but not H1N1 or B. Age was inversely associated with seroprotection and seroconversion against H1N1 and with seroconversion to influenza B. CONCLUSION:Based on this sample of older healthy subjects, there were no consistent relationships between VES 13 or obesity and either seroprotection or seroconversion to three influenza vaccine antigens. 10.1016/j.vaccine.2012.03.071
    Production of interferon α and β, pro-inflammatory cytokines and the expression of suppressor of cytokine signaling (SOCS) in obese subjects infected with influenza A/H1N1. Terán-Cabanillas Elí,Montalvo-Corral Maricela,Silva-Campa Erika,Caire-Juvera Graciela,Moya-Camarena Silvia Y,Hernández Jesús Clinical nutrition (Edinburgh, Scotland) BACKGROUND & AIMS:Obesity was recognized as an independent risk factor for morbidity and mortality during last influenza A/H1N1 pandemic. Mechanisms involved in the high mortality risk from obesity during influenza A virus include reduced type I interferon production and delayed pro-inflammatory response, which lead to a higher rate of morbidity and mortality in murine models. In this study, we evaluated the production of type I interferons, pro-inflammatory and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from obese and lean subjects with and without confirmed infection of influenza A/H1N1. The expression levels of the suppressor of cytokine signaling-1 (SOCS1), SOCS3 and nuclear factor-kB were also evaluated. METHODS:Cytokines were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and/or by ELISA in PBMCs stimulated with toll like receptor-3 (TLR-3) and TLR-7 ligands. The mRNA expression of SOCS1 and SOCS3 were evaluated by qRT-PCR. RESULTS:The obese volunteers infected with influenza A/H1N1 showed a diminished ability to produce type I interferon in response to TLR-3 ligand. Interestingly, the pro-inflammatory response was also affected in TLR-3 stimulated PBMCs. Obese influenza-free volunteers showed an increased basal expression of SOCS3, but not SOCS1. During influenza infection, SOCS1 and SOCS3 expression was higher in the lean infected volunteers in contrast to those who were obese infected. CONCLUSIONS:These data suggest that obesity is related to TLR-3 impairment and explain, at least in part, the inadequate immune response of obese individuals during infection with influenza A/H1N1 virus. 10.1016/j.clnu.2013.10.011
    Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: a systematic review and meta-analysis. Fezeu L,Julia C,Henegar A,Bitu J,Hu F B,Grobbee D E,Kengne A-P,Hercberg S,Czernichow S Obesity reviews : an official journal of the International Association for the Study of Obesity The aim of this study was to assess the association between obesity and the risk of intensive care unit (ICU) admission and death among patients hospitalized for influenza A (H1N1) viral infection. A systematic review of the Medline and Cochrane databases using 'obesity', 'hospitalization', 'influenza A viral infection', various synonyms, and reference lists of retrieved articles from January 2009 to January 2010. Studies comparing the prevalence of obesity among patients with confirmed infection for influenza A virus and who were either hospitalized or admitted to ICU/died were included. A total of 3059 subjects from six cross-sectional studies, who were hospitalized for influenza A (H1N1) viral infection, were included in this meta-analysis. Severely obese H1N1 patients (body mass index ≥ 40 kg m(-2), n = 804) were as twice as likely to be admitted to ICU or die (odds ration: 2.01, 95% confidence interval: 1.29-3.14, P < 0.002) compared with H1N1 patients who were not severely obese. Having a body mass index ≥ 30 kg m(-2) was similarly associated with a more than twofold increased risk of ICU admission or death although this did not reach statistical significance (2.14, 0.92-4.99, P < 0.07). This meta-analysis supports the view that obesity is associated with higher risks of ICU admission or death in patients with influenza A (H1N1) infection. Therefore, morbid obese patients should be monitored more intensively when hospitalized. 10.1111/j.1467-789X.2011.00864.x
    Obesity and pro-inflammatory mediators are associated with acute kidney injury in patients with A/H1N1 influenza and acute respiratory distress syndrome. Cruz-Lagunas Alfredo,Jiménez-Alvarez Luís,Ramírez Gustavo,Mendoza-Milla Criselda,García-Sancho Ma Cecilia,Avila-Moreno Federico,Zamudio Pedro,Urrea Francisco,Ortiz-Quintero Blanca,Campos-Toscuento Victoria L,Morán Juan,Barrera Aldo A,Martínez-Briseño David,Fernández-Plata Rosario,Sierra-Vargas Martha Patricia,Muñoz-Perea Carolina,Illescas-Flores Samuel,Bautista Edgar,Suratt Benjamin T,Pérez-Padilla José Rogelio,Zuñiga Joaquín Experimental and molecular pathology BACKGROUND:The obesity has been shown to increase the severity of A/H1N1 infection and the development of acute respiratory distress syndrome (ARDS) and organ involvement. METHODS:Circulating levels of C-peptide, insulin, glucagon, leptin, acute phase reactants (procalcitonin, C-reactive protein, tissue plasminogen activator, and serum amyloids A and P), were measured in samples from 32 critically ill patients with A/H1N1 virus infection, 17 of whom had ARDS complicated by acute kidney injury (AKI) and 15 of whom had ARDS but did not develop AKI. RESULTS:Patients with ARDS and AKI (ARDS/AKI) had higher BMI and higher levels of C-peptide, insulin, leptin, procalcitonin and serum amyloid A compared to those ARDS patient who did not develop AKI. Adjusting for confounding variables using logistic regression analysis, higher levels of C-peptide (>0.75 ng/mL) (OR=64.8, 95% CI = 2.1-1980, p = 0.0006) and BMI>30 Kg/m(2) (OR = 42.0, 95% CI = 1.2-1478, p = 0.04) were significantly associated with the development of AKI in ARDS patients. CONCLUSION:High levels of C-peptide and BMI>30 kg/m(2) were associated with the development of AKI in ARDS patients due to A/H1N1 infection. These metabolic/obesity indicators, together with the profiles of pro-inflammatory acute phase proteins, may be important links between obesity and poor outcomes in A/H1N1 09 infection. 10.1016/j.yexmp.2014.10.006
    High Body Mass Index as a Risk Factor for Hospitalization Due to Influenza: A Case-Control Study. Martín Vicente,Castilla Jesús,Godoy Pere,Delgado-Rodríguez Miguel,Soldevila Nuria,Fernández-Villa Tania,Molina Antonio J,Astray Jenaro,Castro Ady,González-Candelas Fernando,Mayoral José María,Quintana José María,Domínguez Ángela, Archivos de bronconeumologia INTRODUCTION:Obesity has emerged as a significant independent predictor of severity in pandemic influenzaA (H1N1)pdm09. The aim of this study was to investigate the association between body mass index (BMI) and the risk of hospitalization due to influenza. METHODS:Hospitalized patients (n=755) with laboratory-confirmed influenza were individually matched by age, admission/visit date, and province with an outpatient (n=783) with laboratory-confirmed influenza and an outpatient control (n=950). We compared the BMI using conditional logistic regression adjusted for potential confounding factors (aOR). The population attributable fraction (PAF) was calculated. RESULTS:A higher BMI was associated with an increased risk of hospitalization compared to both outpatient cases (aOR=1.11; 95%CI: 1.07-1.16) and outpatient controls (aOR=1.04; 95%CI: 1.01-1.07). Compared with normal weight, obesity type I, obesity type II and obesity type III was associated with a greater likelihood of hospitalization compared with outpatient cases (aOR=1.85, 95%CI: 1.05-3.26; aOR=5.24, 95%CI: 1.94-14.15 and aOR=44.38, 95%CI: 4.47-440.5). Compared with normal weight, obesity type II and obesity type III was associated with a greater likelihood of hospitalization compared with outpatient controls (aOR=4.37, 95%CI: 1.79-10.69 and aOR=4.95, 95%CI: 1.45-16.87). In persons without influenza vaccination, all categories of BMI≥30kg/m(2) were associated with a greater likelihood of hospitalization compared with normal weight in both outpatient cases and outpatient controls. The PAF of hospitalization by influenza due to BMI ranged from 21.9% to 8.5%; in the case of unvaccinated against influenza between 20.5% to 16.9%. CONCLUSION:A high BMI is associated with an increased risk of hospitalization due to influenza. High percentage of hospital admissions are attributable to their BMI, especially in non vaccinated. 10.1016/j.arbres.2015.11.006
    Increased risk of influenza among vaccinated adults who are obese. Neidich S D,Green W D,Rebeles J,Karlsson E A,Schultz-Cherry S,Noah T L,Chakladar S,Hudgens M G,Weir S S,Beck M A International journal of obesity (2005) BACKGROUND:Influenza infects 5-15% of the global population each year, and obesity has been shown to be an independent risk factor for increased influenza-related complications including hospitalization and death. However, the risk of developing influenza or influenza-like illness (ILI) in a vaccinated obese adult population has not been addressed. OBJECTIVE:This study evaluated whether obesity was associated with increased risk of influenza and ILI among vaccinated adults. SUBJECTS AND METHODS:During the 2013-2014 and 2014-2015 influenza seasons, we recruited 1042 subjects to a prospective observational study of trivalent inactivated influenza vaccine (IIV3) in adults. A total of 1022 subjects completed the study. Assessments of relative risk for laboratory confirmed influenza and ILI were determined based on body mass index. Seroconversion and seroprotection rates were determined using prevaccination and 26-35 days post vaccination serum samples. Recruitment criteria for this study were adults 18 years of age and older receiving the seasonal trivalent inactivated influenza vaccine (IIV3) for the years 2013-2014 and 2014-2015. Exclusion criteria were immunosuppressive diseases, use of immunomodulatory or immunosuppressive drugs, acute febrile illness, history of Guillain-Barre syndrome, use of theophylline preparations or use of warfarin. RESULTS:Among obese, 9.8% had either confirmed influenza or influenza-like-illness compared with 5.1% of healthy weight participants. Compared with vaccinated healthy weight, obese participants had double the risk of developing influenza or ILI (relative risk=2.01, 95% CI 1.12, 3.60, P=0.020). Seroconversion or seroprotection rates were not different between healthy weight and obese adults with influenza or ILI. CONCLUSIONS:Despite robust serological responses, vaccinated obese adults are twice as likely to develop influenza and ILI compared with healthy weight adults. This finding challenges the current standard for correlates of protection, suggesting use of antibody titers to determine vaccine effectiveness in an obese population may provide misleading information. 10.1038/ijo.2017.131
    Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals. Ovsyannikova Inna G,White Sarah J,Larrabee Beth R,Grill Diane E,Jacobson Robert M,Poland Gregory A Vaccine Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (50-74 years old) who were immunized with inactivated TIV influenza vaccine that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r=0.23, p=0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p=0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine. 10.1016/j.vaccine.2013.12.009
    Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses. Travanty Emily,Zhou Bin,Zhang Hongbo,Di Y Peter,Alcorn John F,Wentworth David E,Mason Robert,Wang Jieru Journal of virology UNLABELLED:Human alveolar epithelial cells (AECs) and alveolar macrophages (AMs) are the first lines of lung defense. Here, we report that AECs are the direct targets for H1N1 viruses that have circulated since the 2009 pandemic (H1N1pdm09). AMs are less susceptible to H1N1pdm09 virus, but they produce significantly more inflammatory cytokines than AECs from the same donor. AECs form an intact epithelial barrier that is destroyed by H1N1pdm09 infection. However, there is significant variation in the cellular permissiveness to H1N1pdm09 infection among different donors. AECs from obese donors appear to be more susceptible to H1N1pdm09 infection, whereas gender, smoking history, and age do not appear to affect AEC susceptibility. There is also a difference in response to different strains of H1N1pdm09 viruses. Compared to A/California04/09 (CA04), A/New York/1682/09 (NY1682) is more infectious and causes more epithelial barrier injury, although it stimulates less cytokine production. We further determined that a single amino acid residue substitution in NY1682 hemagglutinin is responsible for the difference in infectivity. In conclusion, this is the first study of host susceptibility of human lung primary cells and the integrity of the alveolar epithelial barrier to influenza. Further elucidation of the mechanism of increased susceptibility of AECs from obese subjects may facilitate the development of novel protection strategies against influenza virus infection. IMPORTANCE:Disease susceptibility of influenza is determined by host and viral factors. Human alveolar epithelial cells (AECs) form the key line of lung defenses against pathogens. Using primary AECs from different donors, we provided cellular level evidence that obesity might be a risk factor for increased susceptibility to influenza. We also compared the infections of two closely related 2009 pandemic H1N1 strains in AECs from the same donor and identified a key viral factor that affected host susceptibility, the dominance of which may be correlated with disease epidemiology. In addition, primary human AECs can serve as a convenient and powerful model to investigate the mechanism of influenza-induced lung injury and determine the effect of genetic and epigenetic factors on host susceptibility to pandemic influenza virus infection. 10.1128/JVI.01792-15
    B Cell Activity Is Impaired in Human and Mouse Obesity and Is Responsive to an Essential Fatty Acid upon Murine Influenza Infection. Kosaraju Rasagna,Guesdon William,Crouch Miranda J,Teague Heather L,Sullivan E Madison,Karlsson Erik A,Schultz-Cherry Stacey,Gowdy Kymberly,Bridges Lance C,Reese Lauren R,Neufer P Darrell,Armstrong Michael,Reisdorph Nichole,Milner J Justin,Beck Melinda,Shaikh Saame Raza Journal of immunology (Baltimore, Md. : 1950) Obesity is associated with increased risk for infections and poor responses to vaccinations, which may be due to compromised B cell function. However, there is limited information about the influence of obesity on B cell function and underlying factors that modulate B cell responses. Therefore, we studied B cell cytokine secretion and/or Ab production across obesity models. In obese humans, B cell IL-6 secretion was lowered and IgM levels were elevated upon ex vivo anti-BCR/TLR9 stimulation. In murine obesity induced by a high fat diet, ex vivo IgM and IgG were elevated with unstimulated B cells. Furthermore, the high fat diet lowered bone marrow B cell frequency accompanied by diminished transcripts of early lymphoid commitment markers. Murine B cell responses were subsequently investigated upon influenza A/Puerto Rico/8/34 infection using a Western diet model in the absence or presence of docosahexaenoic acid (DHA). DHA, an essential fatty acid with immunomodulatory properties, was tested because its plasma levels are lowered in obesity. Relative to controls, mice consuming the Western diet had diminished Ab titers whereas the Western diet plus DHA improved titers. Mechanistically, DHA did not directly target B cells to elevate Ab levels. Instead, DHA increased the concentration of the downstream specialized proresolving lipid mediators (SPMs) 14-hydroxydocosahexaenoic acid, 17-hydroxydocosahexaenoic acid, and protectin DX. All three SPMs were found to be effective in elevating murine Ab levels upon influenza infection. Collectively, the results demonstrate that B cell responses are impaired across human and mouse obesity models and show that essential fatty acid status is a factor influencing humoral immunity, potentially through an SPM-mediated mechanism. 10.4049/jimmunol.1601031
    Obesity and influenza associated mortality: evidence from an elderly cohort in Hong Kong. Yang Lin,Chan King Pan,Lee Ruby Siu-Yin,Chan Wai Man,Lai Hak Kan,Thach Thuan Quoc,Chan Kwok Hung,Lam Tai Hing,Peiris J S Malik,Wong Chit Ming Preventive medicine OBJECTIVE:Obesity was not identified as a risk factor for influenza until the recent 2009 H1N1 pandemic. Based on a cohort of 66,820 subjects aged 65 years and over with the follow-up period from July 1998 to December 2010 in Hong Kong, we assessed the modifying effect of obesity on mortality risks specifically attributable to influenza infections (termed as "influenza associated mortality risks"). METHODS:A Cox proportional model with time dependent covariates was adopted to assess the hazard ratio of mortality in each obesity group when influenza activity increased 10% in the community. RESULTS:Hazard ratio of influenza-associated all-cause mortality was 1.081 (95% confidence interval 1.013, 1.154), 1.047 (1.012, 1.084), 0.981 (0.936, 1.028), 1.018 (0.980, 1.058) and 1.062 (0.972, 1.162) in the underweight, normal, overweight, moderate obesity and severe obesity groups, respectively. A similar U shape pattern across the obesity groups was also observed in influenza associated mortality risks of respiratory diseases, pneumonia and influenza. This pattern was more evident among ever smokers, although the influenza effect estimates in each obesity group had overlapping confidence intervals. CONCLUSION:There is some but limited evidence to suggest that underweight and obesity were associated with higher mortality risks of influenza in old population. 10.1016/j.ypmed.2012.11.017
    Evaluation of obesity as an independent risk factor for medically attended laboratory-confirmed influenza. Coleman Laura A,Waring Stephen C,Irving Stephanie A,Vandermause Mary,Shay David K,Belongia Edward A Influenza and other respiratory viruses BACKGROUND:The relationship between obesity and susceptibility to influenza infection in humans is unclear. Morbidly obese people were at an increased risk of complications from 2009 pandemic H1N1 influenza [A(H1N1)pdm09]. OBJECTIVE:The goal of this study was to determine whether medically attended, laboratory-confirmed influenza is independently associated with obesity in adults with acute respiratory illness. PATIENTS/METHODS:  Adults ≥20 years with a medical encounter for acute respiratory illness were recruited from a population cohort during the 2007-2008 (n = 903), 2008-2009 (n = 869), and 2009 pandemic (n = 851) season. Nasopharyngeal swabs were tested for influenza by real-time reverse-transcription polymerase chain reaction. Body mass index (BMI) was calculated using data from the electronic medical record. Logistic regression evaluated the association between influenza and obesity, adjusting for gender, vaccination, age, and high-risk medical condition. RESULTS:Influenza was detected in 50% of patients in 2007-2008, 15% in 2008-2009, and 14% during the 2009 pandemic. Predominant seasonal viruses in this population were A/H3N2 in 2007-2008, and A/H1N1 and B in 2008-2009. Mean (±SD) BMI was 30·58 (±7·31) in patients with influenza and 30·93 (±7·55) in test-negative controls during all seasons. Mean BMI of patients with influenza did not vary by season. After adjusting for confounders, neither obesity nor extreme obesity were associated with influenza by season or for all years combined (OR 0·95: 95% CI 0·75, 1·20 and 1·10: 0·80, 1·52, respectively, for obesity and extreme obesity, all years). CONCLUSIONS:Obesity was not associated with medically attended influenza among adults with acute respiratory illness in this population. 10.1111/j.1750-2659.2012.00377.x
    [Is obesity an adverse prognostic factor for pulmonary manifestations of influenza? Lesson from complicated disease course H1N1]. Zoubková Renata,Máca Jan,Handlos Petr,Rudinská Lenka,Nytra Ivana,Chýlek Václav,Vavrošová Jana Casopis lekaru ceskych Influenza viruses cause annual epidemics that occur at different times in both the northern and southern hemisphere. In cases of seasonal influenza these are usually mild forms of the disease, which rarely lead to death of the patient. Vulnerable groups include the elderly, the young or those with comorbidities, where the virus affects tens of thousands of victims around the world. Occasionally, however, large epidemics appear caused by a dangerous variant of a new virus, which is usually characterized by high contagiousness and pathogenicity (virulence). Consequently, it is often accompanied by a complicated disease course and associated with high mortality. In 2009, a viral pandemic disease marked pH1N1 2009 Influenza A appeared. Even though the initial predictions were far worse, the course of influenza caused by this virus was often complicated by acute respiratory failure in the form of acute respiratory distress syndrome (ARDS). This formed part of the wider multiple organ failure syndrome (MODS). This type of virus often infects younger age groups and is more contagious compared to the seasonal flu. In order to illustrate the complicated forms of viral infections pH1N1 2009 Influenza A we present three case studies which demonstrate complicated pulmonary manifestation, which take the primary form of ARDS.
    Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination. Karlsson Erik A,Hertz Tomer,Johnson Cydney,Mehle Andrew,Krammer Florian,Schultz-Cherry Stacey mBio UNLABELLED:Obesity is a risk factor for developing severe influenza virus infection, making vaccination of utmost importance for this high-risk population. However, vaccinated obese animals and adults have decreased neutralizing antibody responses. In these studies, we tested the hypothesis that the addition of either alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve neutralizing antibody responses and protect obese mice from challenge. Our studies demonstrate that adjuvanted vaccine does increase both neutralizing and nonneutralizing antibody levels compared to vaccine alone. Although obese mice mount significantly decreased virus-specific antibody responses, both the breadth and the magnitude of the responses against hemagglutinin (HA) and neuraminidase (NA) are decreased compared to the responses in lean mice. Importantly, even with a greater than fourfold increase in neutralizing antibody levels, obese mice are not protected against influenza virus challenge and viral loads remain elevated in the respiratory tract. Increasing the antigen dose affords no added protection, and a decreasing viral dose did not fully mitigate the increased mortality seen in obese mice. Overall, these studies highlight that, while the use of an adjuvant does improve seroconversion, vaccination does not fully protect obese mice from influenza virus challenge, possibly due to the increased sensitivity of obese animals to infection. Given the continued increase in the global obesity epidemic, our findings have important implications for public health. IMPORTANCE:Vaccination is the most effective strategy for preventing influenza virus infection and is a key component for pandemic preparedness. However, vaccines may fail to provide optimal protection in high-risk groups, including overweight and obese individuals. Given the worldwide obesity epidemic, it is imperative that we understand and improve vaccine efficacy. No work to date has investigated whether adjuvants increase the protective capacity of influenza vaccines in the obese host. In these studies, we show that adjuvants increased the neutralizing and nonneutralizing antibody responses during vaccination of lean and obese mice to levels considered "protective," and yet, obese mice still succumbed to infection. This vulnerability is likely due to a combination of factors, including the increased susceptibility of obese animals to develop severe and even lethal disease when infected with very low viral titers. Our studies highlight the critical public health need to translate these findings and better understand vaccination in this increasing population. 10.1128/mBio.01144-16
    Epidemiology of severe influenza outcomes among adult patients with obesity in Detroit, Michigan, 2011. Martin Emily T,Archer Carolyn,McRoberts John,Kulik Janice,Thurston Taylor,Lephart Paul,Kaye Keith S Influenza and other respiratory viruses We conducted a retrospective cohort study to evaluate the impact of obesity on influenza disease severity. Individuals with obesity were more likely to have lower pulmonary disease manifestations [OR=1·97 (95% CI 1·05, 3·69), P=0·03] and to be admitted to an inpatient ward [OR=2·93 (95% CI 1·50, 5·71), P=0·002] when compared with non-obese individuals. Among admitted individuals, persons with obesity were more likely to require a lengthy hospital stay [OR=3·86 (95% CI 1·03, 14·42), P=0·045]. Five of the six deaths in study subjects occurred in persons with obesity. 10.1111/irv.12115
    [Pharmacoepidemiological study of the course of influenza and other acute respiratory viral infections in risk groups]. Bulgakova V A,Poromov A A,Grekova A I,Pshenichnaya N Yu,Selkova E P,Lvov N I,Leneva I A,Shestakova I V,Maleev V V Terapevticheskii arkhiv AIM:To identify risk factors (RFs) for the development of bacterial complications and the prolonged course of influenza and other acute respiratory viral infections (ARVIs) among inpatients treated in Russian healthcare facilities in the post-pandemic period; to determine the clinical presentation of the disease (flu-like syndrome) in risk-group people and to evaluate the efficacy of antiviral therapy with arbidol (umifenovir). MATERIAL AND METHODS:The investigators retrospectively analyzed randomly selected medical records of inpatients with influenza and other ARVI in 88 hospitals from 50 regions of the Russian Federation: those of 3532 and 1755 patients in the 2010-2011 and 2014-2015 seasons, respectively, by applying parametric and nonparametric statistical methods. RESULTS:The built database of patients with influenza-like syndrome contained data from the histories of 2072 men and 2537 women, of whom there were 317 (12.49%) pregnant women; gender evidence was not given in the medical records for 678 patients. 382 (7.2%) were vaccinated against influenza. 1528 (28.9%) people were admitted to hospital with various complications. Information on laboratory tests was available in 1691 (31.98%) patients; of these, 1291 (76.4%) were detected to have influenza and other respiratory viruses. Influenza viruses were found in 1026 (60.7%) examinees; influenza A viruses in 712 (42.1%) people while pandemic strain of swine influenza A/H1N1 and A/H3N2 viruses was detected in 487 (28.8%) and 107 (6.3%) patients, respectively; influenza A subtype was indicated in 118 (7%) persons with laboratory-confirmed influenza virus. Influenza B viruses were found in 314 (18.6%) examinees. Other types of respiratory viruses were detected in 265 (15.7%) patients. The body mass index exceeded 30 kg/m2 in 227 (4.3%) patients. Single-factor analysis of variance revealed factors influencing the course of flu-like syndrome and identified risk groups: children younger than 2 years old and adults over 65, pregnant women, and people with chronic somatic diseases and obesity. The high-risk groups exhibited a more severe course of flu-like syndrome than did the patients outside the risk groups. The incidence of complications was higher, especially in the under 2-year-year-old children and in patients with endocrine, metabolic, or respiratory diseases, with a large proportion of complications being pneumonia. The efficacy of antiviral therapy was higher in the elderly, patients with chronic diseases, and pregnant women than in patients not at risk. In patients treated with umifenovir (provided that it was administered in the first 48 hours after disease onset), the duration of fever and frequency of complications proved to be lower than those in patients who did not receive antiviral therapy. CONCLUSION:The FRs for influenza and ARVI complications are patient's age (children under 3 years of age and adults older than 65 years), the presence of chronic somatic diseases, and pregnancy. Patients with endocrine, eating, metabolic (including obesity), circulatory, and respiratory disorders are at high risk for influenza and ARVI complications. Umifenovir therapy substantially reduces the duration of fever and risk of complications, especially in patients with laboratory-confirmed influenza infection. 10.17116/terarkh201789162-71
    Obesity as a risk factor for severe influenza-like illness. Cocoros Noelle M,Lash Timothy L,DeMaria Alfred,Klompas Michael Influenza and other respiratory viruses BACKGROUND:Obesity was recognized as in independent risk factor for influenza during the 2009 H1N1 influenza pandemic. OBJECTIVES:We evaluated the association between body mass index (BMI) and influenza-like illness (ILI) during two non-pandemic influenza seasons (2003-2004 and 2004-2005) and during the spring and fall waves of the 2009 H1N1 pandemic. METHODS:Adults with severe (inpatient) and mild (outpatient) ILI were compared to those without ILI using a case-cohort design. The study was nested among those insured by a single health insurance company, receiving care from a large multispecialty practice. Data were collected from insurance claims and the electronic health record. The primary exposure was obesity (BMI ≥ 30·0 kg/m(2) ). RESULTS:Across three seasons, the crude and adjusted ORs for obesity and severe ILI were 1·65 (95% CI 1·31, 2·08) and 1·23 (95% CI 0·97, 1·57), respectively. An association was observed for those aged 20-59 years (adjusted OR 1·92, 95% CI 1·26, 2·90), but not for those 60 and older (adjusted OR 1·08, 95% CI 0·80, 1·46). The adjusted ORs for obesity and severe ILI in 2003-2004, 2004-2005, and during H1N1 were 1·14 (95% CI 0·80, 1·64), 1·24 (95% CI 0·86, 1·79), and 1·76 (95% CI 0·91, 3·42), respectively. Among those with a Charlson Comorbidity Index score of zero, the adjusted ORs for 2003-2004, 2004-2005, and H1N1 were 1·60 (95% CI 0·93, 2·76), 1·43 (95% CI 0·80, 2·56), and 1·90 (95% CI 0·68, 5·27), respectively. CONCLUSIONS:Our results suggest a small to moderate association between obesity and hospitalized ILI among adults. 10.1111/irv.12156
    Effect of adenovirus and influenza virus infection on obesity. Hur Sun Jin,Kim Doo Hwan,Chun Se Chul,Lee Si Kyung Life sciences The purpose of this review is to provide an overview of the effects of adenovirus and influenza virus infections on obesity in various experimental models. We reviewed studies that were conducted within the past 10 years and were related to virus infection and obesity prevalence. Here, we discuss a different causal relationship between adenovirus and influenza infections with obesity. Adenovirus infection can cause obesity, whereas obesity can be a risk factor for increasing influenza virus infection and increases the risk of morbidity and mortality. The prevalence of obesity due to adenovirus infections may be due to an increase in glucose uptake and reduction in lipolysis caused by an increase in corticosterone secretion. Adenovirus infections may lead to increases in appetite by decreasing norepinephrine and leptin levels and also cause immune dysfunction. The relationship between obesity and influenza virus infection could be summarized by the following features: decreases in memory T-cell functionality and interferon (IFN)-α, IFN-β, and IFN-γ mRNA expression, increases in viral titer and infiltration, and impaired dendritic cell function in obese individuals. Moreover, leptin resistance may play an important role in increasing influenza virus infections in obese individuals. In conclusion, prevention of adenovirus infections could be a good approach for reducing obesity prevalence, and prevention of obesity could reduce influenza virus infections from the point of view of viral infections and obesity. 10.1016/j.lfs.2013.08.016
    Obesity not associated with severity among hospitalized adults with seasonal influenza virus infection. Braun Elise S,Crawford Forrest W,Desai Mayur M,Meek James,Kirley Pam Daily,Miller Lisa,Anderson Evan J,Oni Oluwakemi,Ryan Patricia,Lynfield Ruth,Bargsten Marisa,Bennett Nancy M,Lung Krista L,Thomas Ann,Mermel Elizabeth,Lindegren Mary Lou,Schaffner William,Price Andrea,Chaves Sandra S Infection We examined seasonal influenza severity [artificial ventilation, intensive care unit (ICU) admission, and radiographic-confirmed pneumonia] by weight category among adults hospitalized with laboratory-confirmed influenza. Using multivariate logistic regression models, we found no association between obesity or severe obesity and artificial ventilation or ICU admission; however, overweight and obese patients had decreased risk of pneumonia. Underweight was associated with pneumonia (adjusted odds ratio 1.31; 95 % confidence interval 1.04, 1.64). 10.1007/s15010-015-0802-x
    Severe Obesity in Children May Not Pose Independent Risk for Influenza Complications. Neyer Vickie L,Woo Jessica G,Siegel Robert M Journal of pediatric nursing PURPOSE:Subsets of children are targeted for influenza vaccination due to known conditions that increase the risk of influenza complications. The purpose of this study was to determine if severe obesity in children suggests targeted vaccination. DESIGN AND METHODS:A retrospective chart review of a large Midwestern pediatric hospital identified 188 cases of influenza complications (defined as requiring hospitalization or death) aged 2 to <20 years old from August 1, 2010 through June 30, 2013. Severe obesity was defined as body mass index (BMI) ≥99% for age and gender, with patients grouped by severe obesity status (yes vs. no). Cases were reviewed for previously identified risk conditions for influenza complications (e.g., asthma, pneumonia, diabetes), and were classified as having or not having a known high risk condition. RESULTS:Of 188 cases, 174 (93%) had a high-risk condition, while only 14 (7%) had no known condition. All 14 (100%) with no known high-risk condition had a BMI <99%. All 15 (100%) with BMI ≥99% had a known high-risk condition. The association between severe obesity status and influenza complications was not statistically significant (p = 0.61). CONCLUSIONS:This suggests that severe obesity in children is not an independent high-risk condition for influenza complications defined as requiring hospitalization or resulting in death, once other known influenza risk factors are considered. IMPLICATIONS:Based on this data, clinicians should not target children for influenza vaccination based on weight status. We cannot comment about whether severe obesity represents increased risk for less severe cases of influenza. 10.1016/j.pedn.2018.05.009
    Barriers to influenza vaccine uptake in obese people in Italy: Changes 2005-2013. Barbadoro Pamela,Recanatini Claudia,Ponzio Elisa,Illuminati Diego,D'Errico Marcello M,Prospero Emilia European journal of internal medicine BACKGROUND:Obesity is an independent risk factor for developing flu-related complications. OBJECTIVE:The aim of this study was to analyze influenza vaccine uptake (VU) in the Italian obese, before and after the introduction of obesity among the national recommendations, and to evaluate factors associated to VU. METHODS:The comparison of two editions of the national survey carried out in 2004-2005, before the inclusion of obese people among the specific high risk categories for flu complications, and in 2013, reaching a sample of 21,857 persons who declared to have a BMI>30. Multilevel logistic regression was used to evaluate potential independent predictors of influenza immunization. RESULTS:Influenza vaccination coverage was 27.16% in 2013, versus 31.61% in 2005. A significant reduction of VU was registered after the introduction of obesity among the high risk conditions, for which flu VU was recommended. Regression modeling, both in adults and in older people, confirmed that barriers to VU in 2013 were younger age, medium level of education, absence of chronic disease, smoking habit, and reporting no contacts with GPs during the previous 12months. Among those aged 65 or more, the role of regional policies was associated to VU. CONCLUSIONS:Immunization rates among young obese population are low, especially if not affected by comorbidities. Moreover, a reduction was registered in 2013 with respect to 2005. Flu vaccine uptake among the older population seems to be influenced by regional vaccination strategies. The development of novel strategy is warranted, especially among the young adults. 10.1016/j.ejim.2016.04.015
    [Burden of disease from influenza-like illness among hospital staff and effectiveness of influenza vaccination during the flu epidemic at the beginning of 2015]. Holbach Michael MMW Fortschritte der Medizin BACKGROUND:Extreme obesity in adolescents is considered largely resistant to therapy. The aim of this study was to demonstrate the short- and long-term BMI histories of patients who have successfully participated in an inpatient weight loss program, and to look for factors influencing the very good success. METHODS:For the case series 10 youths were selected, who participated in an inpatient weight reduction program for 6-12 months and who succeeded in reducing BMI for the short and for the long term. The inpatient weight reduction program was based on a lifestyle intervention. Information on BMI (kg/m(2)) per patient are available for time of baseline examination (T0, admission), final examination (T1, end of inpatient treatment) and follow-up (T2, 3-18 years after the beginning of the intervention). Socio-demographic data were collected within the first consultation (T0). RESULTS:Mean BMI was 41.9 kg/m(2) (BMI-SDS: 3.22) at time of admission. It clearly decreased under therapy and continued decreasing after the end of inpatient treatment. At time of follow-up (T2) 9 patients had a BMI < 30 kg/m(2) and were not any longer rated as obese, 4 patients had normal weight (BMI: 18.5-24.9 g/m(2)). The majority of patients had at least one normal-weight parent, all families had an average or high socioeconomic status (SES) and the majority of young people attended school for at least 10 years. Occurrence of binge eating before the inpatient treatment was rejected by two thirds of patients. CONCLUSIONS:The case series shows that there is a group of patients who have a clear and lasting decrease of BMI and thus benefit for the long term from an inpatient weight reduction program. In literature discussed predictors of long-term weight reduction such as normal weight of parents, high SES of parents and a high school education of the patients were observed in this selective group. In individual cases, a long-term inpatient therapy leading to lasting lifestyle changes should firstly be preferred to bariatric surgery. 10.1007/s15006-016-8607-0
    Obesity Impairs the Adaptive Immune Response to Influenza Virus. Green William D,Beck Melinda A Annals of the American Thoracic Society Influenza, a highly contagious respiratory tract infection, affects millions of adults and children each year. Several high-risk populations include children, the elderly, the immunocompromised, and recently the obese. Given the dramatic rise in obesity over the past few decades, this increased risk for influenza infection poses a serious public health threat because nearly 500 million adults and children worldwide are classified as obese. Obesity impairs the immune response to influenza and influenza vaccination through alterations of the cellular immune system. Compared with vaccinated healthy-weight adults, vaccinated obese adults have twice the risk of influenza or influenza-like illness despite equal serological response to vaccination. This challenges the current standard of protection for influenza and suggests that further vaccination methods or therapeutics are required to combat this virulent respiratory virus. 10.1513/AnnalsATS.201706-447AW
    Obesity Increases the Duration of Influenza A Virus Shedding in Adults. Maier Hannah E,Lopez Roger,Sanchez Nery,Ng Sophia,Gresh Lionel,Ojeda Sergio,Burger-Calderon Raquel,Kuan Guillermina,Harris Eva,Balmaseda Angel,Gordon Aubree The Journal of infectious diseases Epidemiologic studies indicate that obesity increases the risk of severe complications and death from influenza virus infections, especially in elderly individuals. This work investigates the effect of obesity on the duration of viral shedding within household transmission studies in Managua, Nicaragua, over 3 seasons (2015-2017). Symptomatic obese adults were shown to shed influenza A virus 42% longer than nonobese adults (adjusted event time ratio [ETR], 1.42; 95% confidence interval [CI], 1.06-1.89); no association was observed with influenza B virus shedding duration. Even among paucisymptomatic and asymptomatic adults, obesity increased the influenza A shedding duration by 104% (adjusted ETR, 2.04; 95% CI, 1.35-3.09). These findings suggest that obesity may play an important role in influenza transmission. 10.1093/infdis/jiy370
    Underweight, overweight, and obesity as independent risk factors for hospitalization in adults and children from influenza and other respiratory viruses. Moser Joe-Ann S,Galindo-Fraga Arturo,Ortiz-Hernández Ana A,Gu Wenjuan,Hunsberger Sally,Galán-Herrera Juan-Francisco,Guerrero María Lourdes,Ruiz-Palacios Guillermo M,Beigel John H, Influenza and other respiratory viruses BACKGROUND:The relationship between obesity and risk of complications described during the 2009 influenza pandemic is poorly defined for seasonal influenza and other viral causes of influenza-like illness (ILI). METHODS:An observational cohort of hospitalized and outpatient participants with ILI was conducted in six hospitals in Mexico. Nasopharyngeal swabs were tested for influenza and other common respiratory pathogens. RESULTS:A total of 4778 participants were enrolled in this study and had complete data. A total of 2053 (43.0%) had severe ILI. Seven hundred and seventy-eight (16.3%) were positive for influenza, 2636 (55.2%) were positive for other viral respiratory pathogens, and 1364 (28.5%) had no respiratory virus isolated. Adults with influenza were more likely to be hospitalized if they were underweight (OR: 5.20), obese (OR: 3.18), or morbidly obese (OR: 18.40) compared to normal-weight adults. Obese adults with H1N1 had a sixfold increase in odds of hospitalization over H3N2 and B (obese OR: 8.96 vs 1.35, morbidly obese OR: 35.13 vs 5.58, respectively) compared to normal-weight adults. In adults with coronavirus, metapneumovirus, parainfluenza, and rhinovirus, participants that were underweight (OR: 4.07) and morbidly obese (OR: 2.78) were more likely to be hospitalized as compared to normal-weight adults. All-cause influenza-like illness had a similar but less pronounced association between underweight or morbidly obesity and hospitalization. CONCLUSIONS:There is an increased risk of being hospitalized in adult participants that are underweight or morbidly obese, regardless of their viral pathogen status. Having influenza, however, significantly increases the odds of hospitalization in those who are underweight or morbidly obese. 10.1111/irv.12618