Influenza Outcomes Research Articles

LysoPE mediated by respiratory microorganism Aeromicrobium camelliae alleviates H9N2 challenge in mice

Influenza remains a severe respiratory illness that poses significant global health threats. Recent studies have identified distinct microbial communities within the respiratory tract, from nostrils to alveoli. This research explores specific anti-influenza respiratory microbes using a mouse model supported by 16S rDNA sequencing and untargeted metabolomics. The study found that transferring respiratory microbes from mice that survived H9N2 influenza to antibiotic-treated mice enhanced infection resistance. Notably, the levels of Aeromicrobium were significantly higher in the surviving mice. Mice pre-treated with antibiotics and then inoculated with Aeromicrobium camelliae showed reduced infection severity, as evidenced by decreased weight loss, higher survival rates, and lower lung viral titres. Metabolomic analysis revealed elevated LysoPE (16:0) levels in mildly infected mice. In vivo and in vitro experiments indicated that LysoPE (16:0) suppresses inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX2) expression, enhancing anti-influenza defences. Our findings suggest that Aeromicrobium camelliae could serve as a potential agent for influenza prevention and a prognostic marker for influenza outcomes.

Taking AIM at Influenza: The Role of the AIM2 Inflammasome.

Influenza A viruses (IAV) are dynamic and highly mutable respiratory pathogens that present persistent public health challenges. Inflammasomes, as components of the innate immune system, play a crucial role in the early detection and response to infections. They react to viral pathogens by triggering inflammation to promote immune defences and initiate repair mechanisms. While a strong response is necessary for early viral control, overactivation of inflammasomes can precipitate harmful hyperinflammatory responses, a defining characteristic observed during severe influenza infections. The Absent in Melanoma 2 (AIM2) inflammasome, traditionally recognised for its role as a DNA sensor, has recently been implicated in the response to RNA viruses, like IAV. Paradoxically, AIM2 deficiency has been linked to both enhanced and reduced vulnerability to IAV infection. This review synthesises the current understanding of AIM2 inflammasome activation during IAV and explores its clinical implications. Understanding the nuances of AIM2's involvement could unveil novel therapeutic avenues for mitigating severe influenza outcomes.

Influenza vaccine effectiveness in immunocompromised patients with cancer: A Danish nationwide register‐based cohort study

AbstractBackgroundInfluenza vaccination is free of charge for Danish citizens with acquired immunodeficiency but recommendations do not specifically target patients with cancer. This study investigated whether influenza vaccination reduces the main outcome of overall mortality and the secondary outcomes of influenza requiring treatment, pneumonia, myocardial infarction, stroke, heart failure, and venous thromboembolism in patients with cancer.MethodsThis was a register‐based nationwide cohort study. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for overall mortality and secondary outcomes were estimated using Cox proportional hazards models. Analyses were conducted separately for four subgroups: patients aged <65 years with solid tumors, patients aged ≥65 years with solid tumors, patients aged <65 years with hematological cancer, and patients aged ≥65 years with hematological cancer.ResultsA total of 53,249 adult patients with solid tumors who received chemotherapy and 22,182 adult patients with hematological cancer were followed for up to five influenza seasons in the study period of 2007–2018. In the main analysis covering December–March, influenza vaccination was associated with reduced overall mortality in all four subgroups. The reduction was most pronounced in patients with hematological cancer aged <65 years (aHR, 0.66; 95% CI, 0.51–0.87) and smallest in patients with solid tumors aged <65 years (aHR, 0.91; 95% CI, 0.84–0.99). In sensitivity analyses covering January–March, the aHR was 0.87 (95% CI, 0.65–1.16) in patients with hematological cancer aged <65 years and 1.01 (95% CI, 0.92–1.10) in patients with solid tumors aged <65 years. Results for the secondary outcomes were inconclusive.ConclusionsThe results of this study cannot reject that influenza vaccination reduces overall mortality in immunocompromised patients with cancer. The results must be interpreted with caution because of potential unmeasured confounding, which can result in the overestimation of influenza vaccine effectiveness.

Outcomes of COVID-19 and Influenza in Cerebral Palsy Patients Hospitalized in the United States: Comparative Study of a Nationwide Database.

Patients with cerebral palsy (CP) are particularly vulnerable to respiratory infections, yet comparative outcomes between COVID-19 and influenza in this population remain underexplored. Using the National Inpatient Sample from 2020-2021, we performed a retrospective analysis of hospital data for adults with CP diagnosed with either COVID-19 or influenza. The study aimed to compare the outcomes of these infections to provide insights into their impact on this vulnerable population. We assessed in-hospital mortality, complications, length of stay (LOS), hospitalization costs, and discharge dispositions. Multivariable logistic regression and propensity score matching were used to adjust for confounders, enhancing the analytical rigor of our study. The study cohort comprised 12,025 patients-10,560 with COVID-19 and 1465 with influenza. COVID-19 patients with CP had a higher in-hospital mortality rate (10.8% vs. 3.1%, p = 0.001), with an adjusted odds ratio of 3.2 (95% CI: 1.6-6.4). They also experienced an extended LOS by an average of 2.7 days. COVID-19 substantially increases the health burden for hospitalized CP patients compared to influenza, as evidenced by higher mortality rates, longer hospital stays, and increased costs. These findings highlight the urgent need for tailored strategies to effectively manage and reduce the impact of COVID-19 on this high-risk group.

The relative effectiveness of a high-dose quadrivalent influenza vaccine versus standard-dose quadrivalent influenza vaccines in older adults in France: a retrospective cohort study during the 2021–2022 influenza season

ObjectivesHigh-dose quadrivalent influenza vaccine (HD-QIV) was introduced during the 2021/2022 influenza season in France for adults aged ≥65 years as an alternative to standard-dose quadrivalent influenza vaccine (SD-QIV). The aim of this study is to estimate the relative vaccine effectiveness of HD-QIV vs. SD-QIV against influenza-related hospitalizations in France. MethodsCommunity-dwelling individuals aged ≥65 years with reimbursed influenza vaccine claims during the 2021/2022 influenza season were included in the French national health insurance database. Individuals were followed up from vaccination day to 30 June 2022, nursing home admission or death date. Baseline socio-demographic and health characteristics were identified from medical records over the five previous years. Hospitalizations for influenza and other causes were recorded from 14 days after vaccination until the end of follow-up. HD-QIV and SD-QIV vaccinees were matched using 1:4 propensity score matching with an exact constraint on age group, sex, week of vaccination, and region. Incidence rate ratios were estimated using zero-inflated Poisson or zero-inflated negative binomial regression models. ResultsWe matched 405 385 HD-QIV to 1 621 540 SD-QIV vaccinees. HD-QIV was associated with a 23.3% (95% CI, 8.4–35.8) lower rate of influenza hospitalizations compared with SD-QIV (69.5/100 000 person years vs. 90.5/100 000 person years). Post-matching, we observed higher rates in the HD-QIV group for hospitalizations non-specific to influenza and negative control outcomes, suggesting residual confounding by indication. DiscussionHD-QIV was associated with lower influenza-related hospitalization rates vs. SD-QIV, consistent with existing evidence, in the context of high SARS-CoV-2 circulation in France and likely prioritization of HD-QIV for older/more comorbid individuals.

Genetically Predicted Peripheral Immune Cells Mediate the Effect of Gut Microbiota on Influenza Susceptibility.

The communication mechanism of the gut-lung axis has received increasing attention in recent years, particularly in acute respiratory infectious diseases such as influenza. The peripheral immune system serves as a crucial bridge between the gut and the lungs, two organs that are not in close proximity to each other. However, the specific communication mechanism involving gut microbiota, immune cells, and their anti-influenza effects in the lung remains to be further elucidated. In this study, the effects of 731 species of peripheral immune cells and 211 different gut microbiota on influenza outcomes were analyzed using a two-sample Mendelian randomization analysis. After identifying specific species of gut microbiota and peripheral immune cells associated with influenza outcomes, mediation analyses were conducted to determine the mediating effects of specific immune cells in the protective or injurious effects of influenza mediated by gut microbiota. 19 species of gut microbiota and 75 types of peripheral immune cells were identified as being associated with influenza susceptibility. After rigorous screening, 12 combinations were analyzed for mediated effects. Notably, the down-regulation of CD64 on CD14- CD16- cells mediated 21.10% and 18.55% of the protective effect of Alcaligenaceae and Dorea against influenza, respectively. In conclusion, focusing on influenza, this study genetically inferred different types of gut microbiota and peripheral immune cells to determine their protective or risk factors. Furthermore, mediation analysis was used to determine the proportion of mediating effects of peripheral immune cells in gut microbiota-mediated susceptibility to influenza. This helps elucidate the gut-lung axis mechanism by which gut microbiota affects influenza susceptibility from the perspective of regulation of peripheral immune cells.

Evaluating equity-promoting interventions to prevent race-based inequities in influenza outcomes.

Seasonal influenza hospitalizations pose a considerable burden in the United States, with BIPOC (Black, Indigenous, and other People of Color) communities being disproportionately affected. To determine and quantify the effects of different types of mitigation strategies on inequities in influenza outcomes (symptomatic infections and hospitalizations). In this simulation study, we fit a race-stratified agent-based model of influenza transmission to demographic and hospitalization data of the United States. We consider five racial-ethnic groups: non-Hispanic White persons, non- Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons. We tested five idealized equity-promoting interventions to determine their effectiveness in reducing inequity in influenza outcomes. The interventions assumed (i) equalized vaccination rates, (ii) equalized comorbidities, (iii) work-risk distribution proportional to the distribution of the population, (iv) reduced work contacts for all, or (v) a combination of equalizing vaccination rates and comorbidities and reducing work contacts. Reduction in symptomatic or hospitalization risk ratios, defined as the ratio of the number of symptomatic infections (hospitalizations respectively) in each age- and racial-ethnic group and their corresponding white counterpart. We also evaluated the reduction in the absolute mean number of symptomatic infections or hospitalizations in each age- and racial-ethnic group compared to the fitted scenario (baseline). Our analysis suggests that symptomatic infections were equalized and reduced (by up to 17% in BIPOC adults aged 18-49) by strategies reducing work contacts or equalizing vaccination rates. Reducing comorbidities resulted in significant decreases in hospitalizations, with a reduction of over 40% in BIPOC groups. All tested interventions reduced the inequity in influenza hospitalizations in all racial-ethnic groups, but interventions reducing comorbidities in marginalized populations were the most effective. Notably, these interventions resulted in better outcomes across all racial-ethnic groups, not only those prioritized by the interventions. In this simulation modeling study, equalizing vaccination rates and reducing number of work contacts (which are relatively simple strategies to implement) reduced the both the inequity in hospitalizations and the absolute number of symptomatic infections and hospitalizations in all age and racial-ethnic groups.

Cost-effectiveness of COVID rapid diagnostic tests for patients with severe/critical illness in low- and middle-income countries: A modeling study.

Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice. We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza. COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs.

Number of Influenza Risk Factors Informs an Adult's Increased Potential of Severe Influenza Outcomes: A Multiseason Cohort Study From 2015 to 2020.

While studies have evaluated factors influencing the risk of severe influenza outcomes, there is limited evidence on the additive impact of having multiple influenza risk factors and how this varies by age. Patients ≥18 years of age in the United States were evaluated retrospectively in 5 seasonal cohorts during the 2015-2020 influenza seasons. Patient-level electronic medical records linked to pharmacy and medical claims were used to ascertain covariates and outcomes. Multivariable logistic regression models were fitted for the overall population and by age subgroups to evaluate the association of demographic and clinical characteristics with odds of influenza-related medical encounters (ICD-10 codes J09*-J11*). The logistic regression models included sex, race/ethnicity, geographic region, baseline health care resource use, vaccination status, specific high-risk comorbidities, number of influenza risk factors, body mass index, and smoking status. Odds ratios from each of the 5 seasons were summarized via fixed effect meta-analysis. Season cohort sizes ranged from 887 260 to 3 628 168 adults. Of all patient characteristics evaluated, an individual's cumulative number of high-risk influenza conditions, as defined per the Centers for Disease Control and Prevention, was the most predictive of an increased probability of having an influenza-related medical encounter overall and across age groups. For adults of any age, odds ratios for influenza hospitalization ranged from 1.8 (95% CI, 1.7-2.0) for 1 risk factor to 6.4 (95% CI, 5.8-7.0) for ≥4 risk factors. These results show that a simple measure such as the number of influenza risk factors can be highly informative of an adult's potential for severe influenza outcomes.

Impact of obstructive sleep apnea on clinical outcomes of hospitalization due to influenza in children: A propensity score-matched analysis of the US Nationwide Inpatient Sample 2005-2018.

Previous studies have explored the association between obstructive sleep apnea (OSA) and clinical outcomes of influenza in adults, whereas limited research examined this relationship in pediatric populations. This study aimed to evaluate the clinical impact of OSA on the outcomes of pediatric influenza hospitalizations. This was a population-based, retrospective study. Data of children aged 1-19 years hospitalized for influenza infection were extracted from the United States (US) Nationwide Inpatient Sample Database 2005-2018. Univariable and multivariable regression analyses determined associations between OSA, length of stay (LOS), total hospital costs, pneumonia, and life-threatening events. After propensity-score matching, a total of 2100 children were analyzed. The logistic analysis revealed that children with OSA had a significantly increased LOS (β = 2.29 days; 95% confidence interval,CI: 1.01-3.57, p < .001) and total hospital costs (β = 26.06 thousand dollars; 95% CI: 6.62-45.51, p = .009), and higher odds of pneumonia (aged 6-10 years: odds ratio [OR] = 1.52; 95% CI: 1.01-2.27, p = .043; aged ≥ 11 years: OR = 1.83; 95% CI: 1.33-2.53, p < .001). During influenza admissions, children with OSA had longer LOS, higher hospital costs, and an increased risk of pneumonia compared to those without OSA. These findings underscore the importance of recognizing and managing OSA in influenza-related infections among children.

Faecalibacterium duncaniae as a novel next generation probiotic against influenza.

The gut-lung axis is critical during viral respiratory infections such as influenza. Gut dysbiosis during infection translates into a massive drop of microbially produced short-chain fatty acids (SCFAs). Among them, butyrate is important during influenza suggesting that microbiome-based therapeutics targeting butyrate might hold promises. The butyrate-producing bacterium Faecalibacterium duncaniae (formerly referred to as F. prausnitzii) is an emerging probiotic with several health-promoting characteristics. To investigate the potential effects of F. duncaniae on influenza outcomes, mice were gavaged with live F. duncaniae (A2-165 or I-4574 strains) five days before infection. Supplementation of F. duncaniae was associated with less severe disease, a lower pulmonary viral load, and lower levels of lung inflammation. F. duncaniae supplementation impacted on gut dysbiosis induced by infection, as assessed by 16S rRNA sequencing. Interestingly, F. duncaniae administration was associated with a recovery in levels of SCFAs (including butyrate) in infected animals. The live form of F. duncaniae was more potent that the pasteurized form in improving influenza outcomes. Lastly, F. duncaniae partially protected against secondary (systemic) bacterial infection. We conclude that F. duncaniae might serve as a novel next generation probiotic against acute viral respiratory diseases.

Shotgun metagenomics and systemic targeted metabolomics highlight indole-3-propionic acid as a protective gut microbial metabolite against influenza infection

ABSTRACT The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, we used high-resolution shotgun metagenomics and targeted metabolomic analysis to characterize influenza-associated changes in the composition and metabolism of the mouse gut microbiota. We observed several taxonomic-level changes on day (D)7 post-infection, including a marked reduction in the abundance of members of the Lactobacillaceae and Bifidobacteriaceae families, and an increase in the abundance of Akkermansia muciniphila. On D14, perturbation persisted in some species. Functional scale analysis of metagenomic data revealed transient changes in several metabolic pathways, particularly those leading to the production of short-chain fatty acids (SCFAs), polyamines, and tryptophan metabolites. Quantitative targeted metabolomics analysis of the serum revealed changes in specific classes of gut microbiota metabolites, including SCFAs, trimethylamine, polyamines, and indole-containing tryptophan metabolites. A marked decrease in indole-3-propionic acid (IPA) blood level was observed on D7. Changes in microbiota-associated metabolites correlated with changes in taxon abundance and disease marker levels. In particular, IPA was positively correlated with some Lactobacillaceae and Bifidobacteriaceae species (Limosilactobacillus reuteri, Lactobacillus animalis) and negatively correlated with Bacteroidales bacterium M7, viral load, and inflammation markers. IPA supplementation in diseased animals reduced viral load and lowered local (lung) and systemic inflammation. Treatment of mice with antibiotics targeting IPA-producing bacteria before infection enhanced viral load and lung inflammation, an effect inhibited by IPA supplementation. The results of this integrated metagenomic-metabolomic analysis highlighted IPA as an important contributor to influenza outcomes and a potential biomarker of disease severity.

Clinical features and outcomes of influenza and RSV coinfections: a report from Canadian immunization research network serious outcomes surveillance network

BackgroundInfluenza and RSV coinfections are not commonly seen but are concerning as they can lead to serious illness and adverse clinical outcomes among vulnerable populations. Here we describe the clinical features and outcomes of influenza and RSV coinfections in hospitalized adults.MethodsA cohort study was performed with pooled active surveillance in hospitalized adults ≥ 50 years from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) during the 2012/13, 2013/14, and 2014/15 influenza seasons. Descriptive statistics summarized the characteristics of influenza/RSV coinfections. Kaplan-Meier estimated the probability of survival over the first 30 days of hospitalization.ResultsOver three influenza seasons, we identified 33 cases of RSV and influenza coinfection, accounting for 2.39 cases per 1,000 hospitalizations of patients with acute respiratory illnesses. Adults aged 50 + years commonly reported cough (81.8%), shortness of breath (66.7%), sputum production (45.5%), weakness (33.3%), fever (27.3%), and nasal congestion (24.2%) as constitutional and lower respiratory tract infection symptoms. The mortality rate was substantial (12.1%), and age, comorbidity burden, and frailty were associated with a higher risk for adverse clinical outcomes.ConclusionsOlder adults are at higher risk for complications from influenza and RSV coinfections, especially those over 65 with a high comorbidity burden and frailty.

Comparative Clinical Assessment and Risk Stratification of COVID-19 and Influenza Infections in Adults and Children: A Comprehensive Systematic Review and Meta-Analysis.

This study aimed to compare the clinical risks and outcomes of COVID-19 and influenza. The search for relevant articles was conducted using both a database search method and a manual search, which involved searching through the reference lists of articles related to the topic for additional studies. The Quality assessment was carried out using the Newcastle Ottawa tool, and the data analysis was conducted using the Review Manager Software (RevMan 5.4.1). The meta-analysis results indicated that COVID-19 patients had similar lengths of hospital stays (SMD: -0.25; 95% CI: -0.60-0.11; p=0.17). However, COVID-19 patients had significantly higher mortality rates (RR: 0.28; 95% CI: 0.21-0.37; p<0.0001), in-hospital complications (RR: 0.57; 95% CI: 0.50-0.65; p<0.00001), intensive care unit (ICU) admissions (OR: 0.48; 95% CI: 0.37-0.61; p<0.00001), length of ICU stay (SMD: -0.45; 95% CI: -0.83-0.06; p=0.02), and mechanical ventilation use (OR: 0.36; 95% CI: 0.28-0.46; p<0.00001). The findings suggested that COVID-19 was more severe than influenza. Therefore, "flu-like" symptoms should not be dismissed without a clear diagnosis, especially during the winter when influenza is more prevalent.

Pleural macrophages translocate to the lung during infection to promote improved influenza outcomes.

Seasonal influenza results in 3 to 5 million cases of severe disease and 250,000 to 500,000 deaths annually. Macrophages have been implicated in both the resolution and progression of the disease, but the drivers of these outcomes are poorly understood. We probed mouse lung transcriptomic datasets using the Digital Cell Quantifier algorithm to predict immune cell subsets that correlated with mild or severe influenza A virus (IAV) infection outcomes. We identified a unique lung macrophage population that transcriptionally resembled small serosal cavity macrophages and whose presence correlated with mild disease. Until now, the study of serosal macrophage translocation in the context of viral infections has been neglected. Here, we show that pleural macrophages (PMs) migrate from the pleural cavity to the lung after infection with IAV. We found that the depletion of PMs increased morbidity and pulmonary inflammation. There were increased proinflammatory cytokines in the pleural cavity and an influx of neutrophils within the lung. Our results show that PMs are recruited to the lung during IAV infection and contribute to recovery from influenza. This study expands our knowledge of PM plasticity and identifies a source of lung macrophages independent of monocyte recruitment and local proliferation.

Knowledge, attitudes, and practices (KAP) towards seasonal influenza and influenza vaccine among pregnant women in Kyrgyzstan: A cross-sectional study

Influenza is an acute respiratory disease of global importance due to its pandemic potential. Pregnant women are more susceptible to severe illness and adverse outcomes of influenza, and vaccination is the most effective preventive measure for mother and infant. The coverage rate of influenza immunization in Kyrgyzstan is below national targets, despite the World Health Organization’s (WHO) recommendation to prioritize pregnant women for vaccination.This study sought to understand drivers and barriers to influenza vaccine uptake in pregnant women in Kyrgyzstan. A knowledge, attitudes, and practices (KAP) survey was administered from December 2018 to March 2019 to 1,193 pregnant women aged 18 and older attending public health institutions in Kyrgyzstan. Multivariate regression analysis was used to determine the association between variables and outcomes of interest.Nearly half (56.2 %) of the 1,193 participants expressed willingness to be vaccinated during their current pregnancy. Participants with only a high school education had a significantly greater intention for vaccination (95 % CI: 1.4–3.2, p < 0.005) in the multivariate analysis compared to participants with university degrees. Participants with underlying health conditions had a higher intention of being vaccinated (95 % CI: 1.2–1.9, p < 0.005). The main reason for vaccine refusal was the belief that influenza vaccines could have adverse effects on the fetus (28.4 %); belief that vaccines could harm their pregnancy (24.3 %); and concern about vaccine effectiveness (10.6 %).These findings are important as they can inform targeted strategies and policy updates to facilitate influenza vaccine implementation and improve uptake among pregnant women in Kyrgystan, and may support strengthening of national influenza vaccine programs in other countries in Central Asia.

Influenza activity and regional mortality for non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths in the United States and worldwide. While influenza illness is known to be particularly dangerous for frail and elderly patients, the relationship between influenza illness and outcomes in patients with cancer remains largely unknown. The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with non-small cell lung cancer (NSCLC) diagnosed between 2009 and 2015. Influenza-like illness (ILI) activity, provided by the Outpatient Influenza-like Illness Surveillance Network of the Center of Disease for Control and Prevention, was merged with the SEER dataset on the state-month level. Regional monthly mortality rates were compared during low versus high flu months in this ecological cohort study. 202,485 patients with NSCLC from 13 SEER-reporting states were included in the analysis. 53 of 1049 state-months (5.1%) had high flu activity. Monthly mortality rates during low and high flu months were 0.041 (95% CI 0.041–0.042) and 0.051 (95% CI 0.050–0.053), respectively (RR 1.24 [95% CI 1.21–1.27]). The association between ILI activity and mortality was observed at the individual state level and in all clinical and regional subgroups. Increased regional influenza activity is associated with higher mortality rates for patients with NSCLC. Vaccine-directed initiatives and increased awareness amongst providers will be necessary to address the growing but potentially preventable burden of influenza-related lung cancer deaths in the U.S.

Comparison of the clinical features and outcomes of severe seasonal influenza and COVID-19 patients in Tunisia between 2021 and 2022.

We compared patients diagnosed at a SARI (severe acute respiratory infections) surveillance site with COVID-19 and those with seasonal influenza to investigate the clinical differences, common features, and outcomes. We conducted a descriptive, retrospective study in the Medical Intensive Care Unit (ICU) at Abderrahman Mami Hospital between September 2021 and April 2022. Demographic, clinical, and biological data as well as outcomes were recorded for all patients. Among 223 SARI patients, 83 were confirmed COVID-19, and 22 were influenza positive. The distribution according to gender was similar; but patients with influenza were younger than those suffering from COVID-19(mean age 60.36 SD 17.28 vs. 61.88 SD 17.91; P = 0.601). In terms of underlying chronic diseases, the frequency was 84.3% in the COVID-19 group and 72.7% in the influenza group. COVID-19 patients had a longer duration of hospitalization (mean [SD], 9.51 days [8.47 days] vs. 7.33 days [8.82 days]; P = 0.003), and a more frequent need for invasive ventilation (80 [97.4%] vs. 20 [92.3]). Case fatality was also higher among this group compared to the latter (39 [47%] vs. 6 [27.3%], P = 0.01). This exploratory study suggests higher severity of COVID-19 compared to seasonal influenza among SARI hospitalized patients even during the Omicron wave. Further research on higher sample sizes is required to confirm this conclusion.

Association of Chronic Medical Conditions With Severe Outcomes Among Nonpregnant Adults 18-49 Years Old Hospitalized With Influenza, FluSurv-NET, 2011-2019.

Older age and chronic conditions are associated with severe influenza outcomes; however, data are only comprehensively available for adults ≥65 years old. Using data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), we identified characteristics associated with severe outcomes in adults 18-49 years old hospitalized with influenza. We included FluSurv-NET data from nonpregnant adults 18-49 years old hospitalized with laboratory-confirmed influenza during the 2011-2012 through 2018-2019 seasons. We used bivariate and multivariable logistic regression to determine associations between select characteristics and severe outcomes including intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. A total of 16 140 patients aged 18-49 years and hospitalized with influenza were included in the analysis; the median age was 39 years, and 26% received current-season influenza vaccine before hospitalization. Obesity, asthma, and diabetes mellitus were the most common chronic conditions. Conditions associated with a significantly increased risk of severe outcomes included age group 30-39 or 40-49 years (IMV, age group 30-39 years: adjusted odds ratio [aOR], 1.25; IMV, age group 40-49 years: aOR, 1.36; death, age group 30-39 years: aOR, 1.28; death, age group 40-49 years: aOR, 1.69), being unvaccinated (ICU: aOR, 1.18; IMV: aOR, 1.25; death: aOR, 1.48), and having chronic conditions including extreme obesity and chronic lung, cardiovascular, metabolic, neurologic, or liver diseases (ICU: range aOR, 1.22-1.56; IMV: range aOR, 1.17-1.54; death: range aOR, 1.43-2.36). To reduce the morbidity and mortality associated with influenza among adults aged 18-49 years, health care providers should strongly encourage receipt of annual influenza vaccine and lifestyle/behavioral modifications, particularly among those with chronic medical conditions.

895. Multisite Derivation and Validation of Machine Learning Models to Predict Severe Influenza Outcomes in Emergency Department Patients

Abstract Background Millions of Americans are infected by influenza each year. Most experience mild and self-limited illness but a minority progress to severe disease and death. Emergency departments (ED) serve as a frontline for the US health system and must distinguish those at risk for clinical deterioration from those who can be safely discharged to the community. Methods We developed random forest machine learning (ML) models to estimate risk for two severe outcomes in ED patients with influenza: need for inpatient care within 72 hours and need for critical care within 24 hours. Both were defined by multidisciplinary consensus using markers of cardiovascular and respiratory dysfunction captured in the electronic health record (EHR). Predictor data were limited to those recorded prior to ED disposition decision (i.e., discharge, hospitalize) and included patient demographics, ED complaint, active medical problems, vital signs and trends, supplemental oxygen use and selected laboratory results. Our cohort was comprised of adult patients who visited one of five EDs in our university health system between 01/01/2017 and 05/18/2022. A development cohort comprised of encounters that occurred before December 2019 was used for model derivation and 10-fold out of sample validation; models were externally validated in the cohort of encounters that occurred afterward. Results Among 8,032 patients with confirmed influenza, incidence of critical care needs at 24 hours was 6.2% (n = 502) and incidence of inpatient care needs at 72 hours was 16.1% (n = 1295). The most common reasons for ED visit were symptoms of upper or lower respiratory tract infection, fever, and shortness of breath. During external validation, models exhibited excellent predictive performance with AUCs of 0.90 (0.87 - 0.94) for critical and 0.89 (95% CI 0.86 -0.92) for inpatient care needs; both were well-calibrated (Brier scores 0.025 and 0.036). Important predictors of severe disease included shortness of breath, increasing respiratory rate and a high number of comorbid diseases. Predictive Model Performance During External Validation. Random forest models predicted risk for critical care needs within 24 hours (red) and inpatient care needs within 72 hours (blue). Overall predictive performance is shown using receiver operating characteristic curves with area under the curve (AUC) in panels A and B; model calibration curves with Brier scores are shown in C and D; predicted probability distributions are shown with kernel density estimation plots in E and F. Conclusion These findings demonstrate that EHR data and ML can be used to risk-stratify patients with influenza early in their hospital course. An important future aim is to integrate ML-driven predictions into clinical decision support at the point of care. Disclosures Jeremiah S. Hinson, MD, PhD, Beckman Coulter: Advisor/Consultant|Beckman Coulter: Grant/Research Support|Beckman Coulter: TriageGO Katherine ZJ Fenstermacher, PhD, Cepheid: Grant/Research Support Richard E. Rothman, MD, PhD, CEPHEID: Advisor/Consultant|Cepheid: Grant/Research Support|Danaher: Grant/Research Support Oluwakemi Badaki-Makun, MD, PhD, Beckman Coulter: Grant/Research Support Scott Levin, PhD, Beckman Coulter: Licenses|Beckman Coulter: Employment|Beckman Coulter: Stocks/Bonds