Influenza-associated Deaths Research Articles

The burden of all-cause mortality following influenza-associated hospitalizations, FluSurv-NET, 2010-2019.

While the estimated number of U.S. influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital versus post-hospital discharge deaths are limited. Using data from the 2010-11 through 2018-19 seasons from the Influenza Hospitalization Surveillance Network, we linked cases to death certificates to identify patients who died from any cause during their influenza hospital stay or within 30 days post discharge. We described demographic and clinical characteristics of patients who died in hospital versus post discharge and characterized locations and causes of death (COD). Among 121,390 cases hospitalized with laboratory-confirmed influenza over 9 seasons, 5.5% died; 76% of deaths were in patients ≥65 years, 71% were non-Hispanic White, and 34% had ≥4 underlying medical conditions. Among all patients with an influenza-associated hospitalization who died, 48% of deaths occurred after hospital discharge; the median days from discharge to death was 9 days (IQR 3-19 days). Post-discharge deaths more often occurred in older patients and among those with underlying medical conditions. Only 37% of patients who died had "influenza" as a COD on their death certificate. Influenza was more frequently listed as a COD among persons who died in-hospital compared with cardiovascular disease among those who died after discharge. All-cause mortality burden is substantial among patients hospitalized with influenza, with almost 50% of deaths occurring within 30 days after hospital discharge. Surveillance systems should consider capture of post-discharge outcomes to better characterize the impact of influenza on all-cause mortality.

Influenza-Associated Excess Mortality and Hospitalization in Germany from 1996 to 2018.

Influenza-associated excess mortality and morbidity is commonly estimated using statistical methods. In Germany, the Robert Koch Institute (RKI) uses the relative mortality distribution method (RMDM) to estimate influenza-associated excess mortality without reporting age-specific values. In order to better differentiate the distribution of the disease burden, a distinction by age is of high relevance. Therefore, we aimed to revise the existing excess mortality model and provide age-specific excess mortality estimates over multiple seasons. We also used the model to determine influenza-associated excess hospitalizations, since the RKI excess hospitalization model is currently based on another approach (i.e., combination of excess physician visits and hospitalized proportion). This study was a retrospective data analysis based on secondary data of the German population from 1996-2018. We adapted the RKI's method of estimating influenza-associated excess mortality with the RMDM and also applied this approach to excess hospitalizations. We calculated the number of excess deaths/hospitalizations using weekly and age-specific data. Data available in Germany are suitable for addressing the restrictions of the RKI's mortality model. In total, we estimated 175,858 (176,482 with age stratification) influenza-associated excess all cause deaths between 1995-1996 and 2017-2018 ranging from 0 (17 with age stratification) in 2005-2006 to 25,599 (25,527 with age stratification) in 2017-2018. Total influenza-associated excess deaths were comparable to RKI's estimates in most seasons. Most excess deaths/hospitalizations occurred in patients aged≥60 years (95.42%/57.49%) followed by those aged 35-59years (3,80%/24,98%). Compared with our model, the RKI hospitalization model implies a substantial underestimation of excess hospitalizations (828,090 vs. 374,200 over all seasons). This is the first study that provides age-specific estimates of influenza-associated excess mortality in Germany. The results clearly show that the main burden of influenza is in the elderly, for whom prevention and control measures should be prioritized.

Excess multi-cause mortality linked to influenza virus infection in China, 2012-2021: a population-based study.

The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations. Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death. There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year. Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.

Estimates of Seasonal Influenza Burden That Could Be Averted by Improved Influenza Vaccines in the Australian Population Aged Under 65 Years, 2015-2019.

The interpretation of relative vaccine effectiveness (rVE) of improved influenza vaccines is complex. Estimation of burden averted is useful to contextualise their potential impact across different seasons. For the population aged under 65 years in Australia, this study estimated the additional morbidity and mortality that could be averted using improved influenza vaccines. We used observed, season-specific (2015-2019) influenza notification and influenza-coded hospitalisation frequencies and published modelled estimates of influenza-associated hospitalisations and deaths that occurred under the prevailing influenza vaccination coverage scenario. After back-calculating to the estimated burden in the population without vaccination, we applied published standard influenza vaccine effectiveness and coverage estimates to calculate the burden potentially averted by standard and improved influenza vaccines. A plausible range of rVE values were used, assuming 50% coverage. The percentage point difference in absolute vaccine effectiveness (VE) of an improved vaccine compared to a standard vaccine is directly proportional to its rVE and inversely proportional to the effectiveness of the standard vaccine. The incremental burden averted by an improved vaccine is a function of both its difference in absolute VE and the severity of the influenza season. Assuming an rVE of 15% with 50% coverage, the improved vaccine was estimated to additionally avert 1517 to 12,641 influenza notifications, 287 to 1311 influenza-coded hospitalisations and 9 to 33 modelled all-cause influenza deaths per year compared to the standard vaccine. Improved vaccines can have substantial clinical and population impact, particularly when the effectiveness of standard vaccines is low, and burden is high.

Uncovering the burden of Influenza in children in Portugal, 2008–2018

BackgroundDespite their higher risk of developing severe disease, little is known about the burden of influenza in Portugal in children aged < 5 years old. This study aims to cover this gap by estimating the clinical and economic burden of severe influenza in children, in Portugal, during ten consecutive influenza seasons (2008/09-2017/18).MethodsWe reviewed hospitalizations in children aged < 5 years old using anonymized administrative data covering all public hospitals discharges in mainland Portugal. The burden of hospitalization and in-hospital mortality directly coded as due to influenza was supplemented by the indirect burden calculated from excess hospitalization and mortality (influenza-associated), estimated for four groups of diagnoses (pneumonia or influenza, respiratory, respiratory or cardiovascular, and all-cause), through cyclic regression models integrating the incidence of influenza. Means were reported excluding the H1N1pdm09 pandemic (2009/10).ResultsThe mean annual number of hospitalizations coded as due to influenza was 189 (41.3 cases per 100,000 children aged < 5 years old). Hospitalization rates decreased with increasing age. Nine-in-ten children were previously healthy, but the presence of comorbidities increased with age. Children stayed, on average, 6.1 days at the hospital. Invasive mechanical ventilation was used in 2.4% of hospitalizations and non-invasive in 3.1%. Influenza-associated excess hospitalizations between 2008 and 2018 were estimated at 1,850 in pneumonia or influenza, 1,760 in respiratory, 1,787 in respiratory or cardiovascular, and 1,879 in all-cause models. A total of 95 influenza-associated excess deaths were estimated in all-cause, 14 in respiratory or cardiovascular, and 9 in respiratory models. Over ten years, influenza hospitalizations were estimated to have cost the National Health Service at least €2.9 million, of which 66.5% from healthy children.ConclusionsInfluenza viruses led to a high number of hospitalizations in children. Most were previously healthy. Results should lead to a reflection on the adequate preventive measures to protect this age group.

Covid-19 and influenza vaccine effectiveness against associated hospital admission and death among individuals over 65 years in Norway: A population-based cohort study, 3 October 2022 to 20 June 2023

BackgroundCo-circulation of SARS-CoV-2 and influenza virus can lead to double epidemics and increased pressure on health systems. To evaluate the effect of both vaccines, we estimated the adjusted vaccine effectiveness (aVE) of influenza and Covid-19 vaccines against related severe disease in the elderly population in Norway during the 2022/2023 season. MethodsIn this population-based cohort study, we included data from the Emergency preparedness register for Covid-19 (Beredt C19) on all individuals ≥ 65 years living in Norway between 3 October 2022 and 20 June 2023. Using Cox-proportional hazard models, we estimated aVE of both influenza and Covid-19 vaccines (bivalent BA.1 and BA.4–5) against associated hospitalisation and death. Vaccine status was included as a time-varying covariate and all models were adjusted for potential confounders, including the other vaccine. ResultsWe identified 2,437 influenza-associated hospitalisations and 178 deaths, alongside 5,824 Covid-19-associated hospitalisations and 621 deaths. The aVE was highest in the first three months after receiving either vaccine. Against influenza-associated hospitalisation the aVE was 34 % (26 %–42 %) among 65–79-year-olds and 40 % (30 %–48 %) among ≥ 80-year-olds, and 6.6 % (−64 %–47 %) and 37 % (0.5 %–61 %) against influenza-associated death, respectively. The aVE against Covid-19-associated hospitalisation was 65 % (61 %–69 %) among 65–79-year-olds and 55 % (49 %–60 %) among ≥ 80-year-olds (compared to having received the vaccine ≥ 180 days ago). Similarly, the aVE against Covid-19-associated death was 68 % (48 %–80 %) and 78 % (65 %–86 %), respectively. For Covid-19 we show a reduction in aVE with time since dose. ConclusionCovid-19 and influenza vaccines reduced the risk of severe disease in the same high-risk population. Ensuring high uptake of both vaccines could thus limit the overall health care burden.

From respiratory diseases to nervous system disorders: Unraveling the certified causes of influenza-associated deaths in Poland from 2000 to 2019.

This study aims to accurately estimate influenza-associated deaths in Poland and their certified cause of death, due to significant discrepancies between official numbers and expected impact. Excess influenza-associated mortality in Poland from 2000 to 2019 was calculated using Seasonal-Trend Decomposition Procedure based on LOESS (STL), which can detect non-linear trends and non-sinusoidal cycles. Excess mortality was then used as an explanatory variable in a model predicting monthly fluctuations of officially recorded causes of death from 2010 to 2019. A total of 142,000 conservative estimates of influenza-associated deaths were identified, representing 1.86% of overall mortality. Only 0.61% of influenza-associated deaths were officially recorded as influenza. Nearly half of certified influenza deaths were attributed to the seasonal baseline mortality, potentially doubling estimated impact based solely on influenza peaks. Influenza-associated deaths were frequently recorded as respiratory diseases (24.36%), with majority attributed to underlying conditions such as cardiovascular diseases (45.31%), cancer (9.06%), or diabetes (2.66%). Influenza-associated deaths were more commonly certified as nervous system diseases (1.84%) or mental disorders (1.04%), rather than influenza itself. There was a noticeable impact of influenza on secondary infections, such as meningococcal and gastrointestinal infections. These findings highlight the importance of improved estimation for informing public health policy decisions.

High Influenza Incidence and Disease Severity Among Children and Adolescents Aged

During the 2022-23 influenza season, early increases in influenza activity, co-circulation of influenza with other respiratory viruses, and high influenza-associated hospitalization rates, particularly among children and adolescents, were observed. This report describes the 2022-23 influenza season among children and adolescents aged <18 years, including the seasonal severity assessment; estimates of U.S. influenza-associated medical visits, hospitalizations, and deaths; and characteristics of influenza-associated hospitalizations. The 2022-23 influenza season had high severity among children and adolescents compared with thresholds based on previous seasons' influenza-associated outpatient visits, hospitalization rates, and deaths. Nationally, the incidences of influenza-associated outpatient visits and hospitalization for the 2022-23 season were similar for children aged <5 years and higher for children and adolescents aged 5-17 years compared with previous seasons. Peak influenza-associated outpatient and hospitalization activity occurred in late November and early December. Among children and adolescents hospitalized with influenza during the 2022-23 season in hospitals participating in the Influenza Hospitalization Surveillance Network, a lower proportion were vaccinated (18.3%) compared with previous seasons (35.8%-41.8%). Early influenza circulation, before many children and adolescents had been vaccinated, might have contributed to the high hospitalization rates during the 2022-23 season. Among symptomatic hospitalized patients, receipt of influenza antiviral treatment (64.9%) was lower than during pre-COVID-19 pandemic seasons (80.8%-87.1%). CDC recommends that all persons aged ≥6 months without contraindications should receive the annual influenza vaccine, ideally by the end of October.

Factors associated to influenza vaccination among hospital’s healthcare workers in the Autonomous Community of Madrid, Spain 2021–2022

Influenza vaccination (IV) aims primarily to protect high-risk groups against severe influenza-associated disease and death. It is recommended in Spain for high-risk groups, including Healthcare workers (HCWs). However, vaccination uptake has been consistently below desirable levels. The objective of this study were to evaluate influenza vaccination coverage using data from the regional vaccination registry, during 2021–2022 season, among HCWs in public hospitals in Autonomous Community of Madrid (CAM) and to explore factors associated with influenza vaccination. We conducted a cross-sectional study using administrative data retrieved from the Regional Department of Health data repositories. A multilevel logistic regression model was designed to estimate Level 1 (individual) and Level 2 (contextual) variables that are associated with HCẂs vaccination. The study population was HCWs from 25 public hospitals in CAM who were active during the period of the influenza 2021–2022 vaccination campaign. The global influenza vaccination coverage (IVC) was 52.1 %. All study Level 1 variables were significantly associated with vaccine uptake. Greater IVC is associated with individual characteristics: female (OR1.14; 95 %CI 1.09–1.19), older age 59–69 years old (OR1.72; 95 %CI 1.60–1.84), born in Spain, medical staff, more than one high-risk condition (OR1.24; 95 %CI 1.10–1.40; respectively) and vaccinated in two previous campaigns (OR25.64; 95 %CI 24.27–27.09). IVC was highest among HCWs celiac disease (65.5 %) followed by diabetes mellitus (65.1 %) and chronic inflammatory disease (64.3 %). The hospital where the study subject worked also showed an effect on the vaccination uptake, although Level 2 variable (hospital complexity) was not positively associated. IVC in HCWs remains suboptimal. These findings may prove useful to tailor strategies to reach specific groups. It is recommended to delve into the identification of factors associated with the HCWs workplace that may have a positive impact on IV.

The Impact of Adjuvanted Influenza Vaccine on Disease Severity in the US: A Stochastic Model.

Influenza can exacerbate underlying medical conditions. In this study, we modelled the potential impact of an egg-based quadrivalent influenza vaccine (QIVe) or adjuvanted QIV (aQIV) on hospitalizations and mortality from influenza-related cardiovascular disease (CVD), respiratory, and other complications in adults ≥65 years of age in the US with underlying chronic conditions. We used a stochastic decision-tree model, with 1000 simulations varying input across predicted ranges. Due to the variable nature of influenza across seasons and differences in published estimates for input parameters, data are presented as 95% confidence intervals. Compared with no vaccination, use of aQIV would prevent 135,450-564,360 hospitalizations and 1612-29,226 deaths across outcomes evaluated. Overall, aQIV prevented 1071-18,388 more hospitalizations and 85-1944 more deaths than QIVe. By routine seasonal vaccination against influenza, a substantial number of severe influenza-associated complications and deaths, caused by direct influenza symptoms or by exacerbation of chronic conditions, can be prevented in high-risk adults ≥65 years of age in the US.

Risk factors for death associated with severe influenza in children and the impact of the COVID-19 pandemic on clinical characteristics.

To summarize the clinical features of severe influenza in children and the high-risk factors for influenza-related deaths and to raise awareness among pediatricians. A retrospective study of clinical manifestations, laboratory tests, and diagnosis and treatment of 243 children with severe influenza admitted to Shenzhen Children's Hospital from January 2009 to December 2022 was conducted. Univariate logistic regression analysis and Boruta analysis were also performed to identify potentially critical clinical characteristics associated with death, and clinically significant were used in further multivariate logistic regression analysis. Subject receiver operating characteristic (ROC) curves were applied to assess the efficacy of death-related independent risk factors to predict death from severe influenza. There were 169 male and 74 female patients with severe influenza, with a median age of 3 years and 2 months and 77.4% of patients under six. There were 46 cases (18.9%) in the death group. The most common pathogen was Influenza A virus (IAV) (81.5%). The most common complication in the death group was influenza-associated acute necrotizing encephalopathy (ANE [52.2%]). Severe influenza in children decreased significantly during the COVID-19 pandemic, with a median age of 5 years, a high predominance of neurological symptoms such as ANE (P = 0.001), and the most common pathogen being H3N2 (P < 0.001). D-dimer, acute respiratory distress syndrome (ARDS), and acute necrotizing encephalopathy (ANE) were significant independent risk factors for severe influenza-associated death. Furthermore, the ROC curves showed that the combined diagnosis of independent risk factors had significant early diagnostic value for severe influenza-related deaths. Neurological disorders such as ANE are more significant in children with severe influenza after the COVID-19 pandemic. Influenza virus infection can cause serious multisystem complications such as ARDS and ANE, and D-dimer has predictive value for early diagnosis and determination of the prognosis of children with severe influenza.

Enhanced targeted influenza vaccines - New evidence shows higher effectiveness in older adults

Seasonal influenza causes a significant burden of disease in the German population and is associated with high societal costs. Persons aged 60 years and older are particularly at risk due to immunosenescence and chronic disease and account for a large proportion of influenza-associated hospitalizations and deaths. Adjuvanted, high-dose, recombinant and cell-based influenza vaccines have been developed to improve the effectiveness compared with conventional vaccines. Recent observational studies show better effectiveness of adjuvanted vaccine over conventional vaccines and similar effectiveness to the high-dose vaccine in older adults. Some countries have already considered the new evidence in their vaccination recommendations for the current or earlier seasons. The availability of the vaccines for older adults should also be ensured in Germany to guarantee a high level of vaccination protection.

Determinants of parental seasonal influenza vaccine hesitancy in the Eastern Mediterranean region: A cross-sectional study.

Seasonal influenza vaccine can reduce the risk of influenza-associated hospitalizations and deaths among children. Given that parents are the primary decision makers, this study examined the parental attitude toward childhood influenza vaccine and identified determinants of vaccine hesitancy (VH) in the Eastern Mediterranean region (EMR). A cross-sectional study was conducted using an anonymous online survey in 14 EMR countries. Parents of children aged 6 months to 18 years were included. The Parent Attitude about Childhood Vaccines (PACV) was used to assess VH. Chi square test and independent t-test were used to test for association of qualitative and quantitative variables, respectively. A structural equations model (SEM) was used to identify direct and indirect determinants of parental VH. Almost half of the parents were hesitant about vaccinating their children against influenza (50.8%). Parental VH was significantly higher among older mothers (37.06 ± 8.8 years, p = 0.006), rural residents (53.6%, p < 0.001), high-income countries residents (50.6%, p < 0.001), and mothers with higher educational levels (52.1%, p < 0.001). Parents of school-aged children (5-9 years) (55.6%, p < 0.001), children free from any comorbidities (52.5%, p < 0.001), children who did not receive routine vaccination at all (51.5%, p = 0.03), children who were not vaccinated against COVID-19 (54.3%, p < 0.001), in addition to parents who were not vaccinated against influenza (57.1%, p < 0.001) were significantly associated with increased likelihood of VH. Parents who were depending on healthcare provider as a source of information regarding vaccines were less likely to report VH (47.9%, p < 0.001), meanwhile those who used social media as their source of health information showed a significantly higher VH (57.2%, p < 0.001). The SEM suggested that mother's age, residence, country income level, child gender, total number of children and source of information regarding vaccines had a direct effect on VH. Meanwhile, parents vaccinated against influenza, children completely or partially vaccinated with routine vaccines and children vaccinated against Coronavirus disease 2019 (COVID-19) had an indirect effect on VH. A high proportion of included parents were hesitant to vaccinate their children against seasonal influenza. This attitude is due to many modifiable and non-modifiable factors that can be targeted to improve vaccination coverage.

Modeling the potential health impacts of delayed strain selection on influenza hospitalization and mortality with mRNA vaccines

BackgroundInfluenza viruses are constantly evolving through antigenic drift, which makes vaccines potentially ill-matched to circulating strains due to the time between strain selection and distribution. mRNA technology could improve vaccine effectiveness (VE) by reducing this time. Significant private and public investments would be required to accommodate accelerated vaccine development and approval. Hence, it is important to understand the potential impact of mRNA technology on influenza hospitalizations and mortality. MethodsWe developed an age-stratified dynamic model of influenza transmission to evaluate the potential impact of increased VE (increased protection against either infection or only hospitalization) on hospitalizations and mortality in the United States. We assume that mRNA technology allows for delaying the time to strain choice, which might increase efficacy, but it does not reduce the time needed for distribution and administration, which might reduce availability. To assess this tradeoff, we evaluated two scenarios where strain choice was delayed until late summer resulting in a more effective vaccine available to (1) all age groups by October, or (2) adults 65 years and older starting in August. ResultsIf not available until October, the vaccine would need a minimum of 95% effectiveness against infection to see a decrease in hospitalizations and deaths in all age groups. When delayed until November, even a 100% effective vaccine had no significant impact. For the elderly, the minimum required VE (against infection) was 50% to reduce hospitalizations and deaths. Moreover, a vaccine with 80% VE against infection available in August for the 65 + age group was better than a 95% effective vaccine available in October for all ages. ConclusionsAs the majority of influenza-associated hospitalizations and deaths are in adults 65 years and older, a combination policy targeting higher VE and coverage for this age group in the short term would be the most efficacious.

Receipt of COVID-19 and seasonal influenza vaccines in California (USA) during the 2021-2022 influenza season.

Despite lower circulation of influenza virus throughout 2020-2022 during the COVID-19 pandemic, seasonal influenza vaccination has remained a primary tool to reduce influenza-associated illness and death. The relationship between the decision to receive a COVID-19 vaccine and/or an influenza vaccine is not well understood. We assessed predictors of receipt of 2021-2022 influenza vaccine in a secondary analysis of data from a case-control study enrolling individuals who received SARS-CoV-2 testing. We used mixed effects logistic regression to estimate factors associated with receipt of seasonal influenza vaccine. We also constructed multinomial adjusted marginal probability models of being vaccinated for COVID-19 only, seasonal influenza only, or both as compared with receipt of neither vaccination. Among 1261 eligible participants recruited between 22 October 2021-22 June 2022, 43% (545) were vaccinated with both seasonal influenza vaccine and >1 dose of a COVID-19 vaccine, 34% (426) received >1 dose of a COVID-19 vaccine only, 4% (49) received seasonal influenza vaccine only, and 19% (241) received neither vaccine. Receipt of >1 COVID-19 vaccine dose was associated with seasonal influenza vaccination (adjusted odds ratio [aOR]: 3.72; 95% confidence interval [CI]: 2.15-6.43); this association was stronger among participants receiving >1 COVID-19 booster dose (aOR = 16.50 [10.10-26.97]). Compared with participants testing negative for SARS- CoV-2 infection, participants testing positive had lower odds of receipt of 2021-2022 seasonal influenza vaccine (aOR = 0.64 [0.50-0.82]). Recipients of a COVID-19 vaccine were more likely to receive seasonal influenza vaccine during the 2021-2022 season. Factors associated with individuals' likelihood of receiving COVID-19 and seasonal influenza vaccines will be important to account for in future studies of vaccine effectiveness against both conditions. Participants who tested positive for SARS-CoV-2 in our sample were less likely to have received seasonal influenza vaccine, suggesting an opportunity to offer influenza vaccination before or after a COVID-19 diagnosis.

Influenza-Associated Excess Mortality by Age, Sex, and Subtype/Lineage: Population-Based Time-Series Study With a Distributed-Lag Nonlinear Model.

Accurate estimation of the influenza death burden is of great significance for influenza prevention and control. However, few studies have considered the short-term harvesting effects of influenza on mortality when estimating influenza-associated excess deaths by cause of death, age, sex, and subtype/lineage. This study aimed to estimate the cause-, age-, and sex-specific excess mortality associated with influenza and its subtypes and lineages in Guangzhou from 2015 to 2018. Distributed-lag nonlinear models were fitted to estimate the excess mortality related to influenza subtypes or lineages for different causes of death, age groups, and sex based on daily time-series data for mortality, influenza, and meteorological factors. A total of 199,777 death certificates were included in the study. The average annual influenza-associated excess mortality rate (EMR) was 25.06 (95% empirical CI [eCI] 19.85-30.16) per 100,000 persons; 7142 of 8791 (81.2%) deaths were due to respiratory or cardiovascular mortality (EMR 20.36, 95% eCI 16.75-23.74). Excess respiratory and cardiovascular deaths in people aged 60 to 79 years and those aged ≥80 years accounted for 32.9% (2346/7142) and 63.7% (4549/7142) of deaths, respectively. The male to female ratio (MFR) of excess death from respiratory diseases was 1.34 (95% CI 1.17-1.54), while the MFR for excess death from cardiovascular disease was 0.72 (95% CI 0.63-0.82). The average annual excess respiratory and cardiovascular mortality rates attributed to influenza A (H3N2), B/Yamagata, B/Victoria, and A (H1N1) were 8.47 (95% eCI 6.60-10.30), 5.81 (95% eCI 3.35-8.25), 3.68 (95% eCI 0.81-6.49), and 2.83 (95% eCI -1.26 to 6.71), respectively. Among these influenza subtypes/lineages, A (H3N2) had the highest excess respiratory and cardiovascular mortality rates for people aged 60 to 79 years (20.22, 95% eCI 14.56-25.63) and ≥80 years (180.15, 95% eCI 130.75-227.38), while younger people were more affected by A (H1N1), with an EMR of 1.29 (95% eCI 0.07-2.32). The mortality displacement of influenza A (H1N1), A (H3N2), and B/Yamagata was 2 to 5 days, but 5 to 13 days for B/Victoria. Influenza was associated with substantial mortality in Guangzhou, occurring predominantly in the elderly, even after considering mortality displacement. The mortality burden of influenza B, particularly B/Yamagata, cannot be ignored. Contrasting sex differences were found in influenza-associated excess mortality from respiratory diseases and from cardiovascular diseases; the underlying mechanisms need to be investigated in future studies. Our findings can help us better understand the magnitude and time-course of the effect of influenza on mortality and inform targeted interventions for mitigating the influenza mortality burden, such as immunizations with quadrivalent vaccines (especially for older people), behavioral campaigns, and treatment strategies.

Mortality associated with Omicron and influenza infections in France before and during the COVID-19 pandemic.

For many deaths associated with influenza and Omicron infections, those viruses are not detected. We applied previously developed methodology to estimate the contribution of influenza and Omicron infections to all-cause mortality in France for the 2014-2015 through the 2018-2019 influenza seasons, and the period between week 33, 2022 and week 12, 2023. For the 2014-2015 through the 2018-2019 seasons, influenza was associated with annual average of 15,654 (95% CI (13,013, 18,340)) deaths, while between week 33, 2022 and week 12, 2023, we estimated 7,851 (5,213, 10,463) influenza-associated deaths and 32,607 (20,794, 44,496) SARS-CoV-2 associated deaths. For many Omicron-associated deaths for cardiac disease, mental&behavioural disorders, and other causes, Omicron infections are not characterised as a contributing cause of death - for example, between weeks 33-52 in 2022, we estimated 23,983 (15,307, 32,620) SARS-CoV-2-associated deaths in France, compared with 12,811 deaths with COVID-19 listed on death certificate. Our results suggest the need for boosting influenza vaccination coverage in different population groups in France, and for wider detection of influenza infections in respiratory illness episodes (including pneumonia) in combination with the use of antiviral medications. For Omicron epidemics, wider detection of Omicron infections in persons with underlying health conditions is needed.

UNDERSTANDING OLDER ADULTS' FLU VACCINE HESITANCY: THE ROLE OF MEDICAL MISINFORMATION

Abstract Influenza persists as a common communicable disease and remains a significant cause of disease burden across the world. Despite preventative therapies, such as influenza vaccination to reduce its spread and transmission, influenza continues to be a source of morbidity and mortality, even in developed countries. For the population over the age of 65, the effects of influenza virus may be more severe when they are compounded by pre-existing conditions and reduced natural immune function.In light of plateauing vaccination rates, a scoping review was conducted to map the literature and determine why seniors aged 65 and above refuse or fail to receive seasonal influenza vaccination. Nine peer-reviewed academic databases covering both social sciences and medical research were searched, along with the grey literature. A total of 6562 references were identified; after the screening process, 118 references were included in the final review. Thematic analysis focused on the broad areas that positively or negatively influence older adults’ decision-making regarding influenza vaccination, and this resulted in five main themes: (1) barriers to obtaining vaccination; (2) social factors; (3) personal characteristics; (4) individual subjectivity; and (5) direct clinical interventions.This review aims to identify gaps in knowledge and synthesize currently available information to make recommendations for future research, policy development and clinical practice. Increasing the vaccination rate among Canadian older adults will contribute to ongoing efforts to reduce the spread of the influenza virus among the population, reducing influenza-associated hospital admissions and deaths.

Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged

The 2022-23 influenza season shows an early rise in pediatric influenza-associated hospitalizations (1). SARS-CoV-2 viruses also continue to circulate (2). The current influenza season is the first with substantial co-circulation of influenza viruses and SARS-CoV-2 (3). Although both seasonal influenza viruses and SARS-CoV-2 can contribute to substantial pediatric morbidity (3-5), whether coinfection increases disease severity compared with that associated with infection with one virus alone is unknown. This report describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the 2021-22 influenza season. Data from two Respiratory Virus Hospitalizations Surveillance Network (RESP-NET) platforms (October 1, 2021-April 30, 2022),§ and notifiable pediatric deaths associated¶ with influenza virus and SARS-CoV-2 coinfection (October 3, 2021-October 1, 2022)** were analyzed. SARS-CoV-2 coinfections occurred in 6% (32 of 575) of pediatric influenza-associated hospitalizations and in 16% (seven of 44) of pediatric influenza-associated deaths. Compared with patients without coinfection, a higher proportion of those hospitalized with coinfection received invasive mechanical ventilation (4% versus 13%; p = 0.03) and bilevel positive airway pressure or continuous positive airway pressure (BiPAP/CPAP) (6% versus 16%; p = 0.05). Among seven coinfected patients who died, none had completed influenza vaccination, and only one received influenza antivirals.†† To help prevent severe outcomes, clinicians should follow recommended respiratory virus testing algorithms to guide treatment decisions and consider early antiviral treatment initiation for pediatric patients with suspected or confirmed influenza, including those with SARS-CoV-2 coinfection who are hospitalized or at increased risk for severe illness. The public and parents should adopt prevention strategies including considering wearing well-fitted, high-quality masks when respiratory virus circulation is high and staying up-to-date with recommended influenza and COVID-19 vaccinations for persons aged ≥6 months.

2319. Analysis of the potential impact of effectiveness and availability of mRNA influenza vaccine on hospitalization and mortality

Abstract Background Influenza viruses constantly change because of antigenic drift. Due to the time currently needed to develop and distribute flu shots, vaccines are often ill-matched to circulating influenza strains. One silver lining of the COVID-19 pandemic was the acceleration of mRNA technology, which could significantly reduce the timeline between strain choice and deployment, potentially increasing vaccine efficacy. Significant private and public investments would be required to accommodate accelerated vaccine development and approval. Hence, it is important to understand the potential impact of mRNA technology on influenza hospitalizations and mortality. Methods We developed a compartmental model stratified by age group to evaluate the potential effect of increased vaccine effectiveness (defined as a two-level measure of protection against infection and hospitalization) on influenza hospitalizations and mortality in the United States. We assume that mRNA technology can only shorten the time from strain choice to distribution but not distribution and administration. Thus, later decisions on vaccine composition would increase effectiveness but reduce availability. To assess this tradeoff, we evaluated two scenarios where strain choice was delayed until summer resulting in a more effective vaccine: (1) available to all age groups in the fall, or (2) available by August but only for adults 65 years and older. Results Assuming current vaccine coverage rates, if not available until October, the vaccine would need a minimum of 80% effectiveness against infection to see a decrease in hospitalizations and deaths (Figures 1A and 1B). When delayed until November, even a 100% effective vaccine could not reduce hospitalizations or deaths (Figures 1C and 1D). For the elderly, a 50% effective vaccine against infection (Figures 1E and 1F) or a vaccine 40% effective against infection and 60% against hospitalization available in late summer was similar to an 80% effective vaccine available in October for all ages. Age-stratified weekly number of influenza-associated hospitalization per 100,000 population and total number of deaths in the United States for an mRNA vaccine that would be available in either October (A and B), November (C and D), or by late summer but only for the 65+ age group (E and F). The Baseline represents the 10-year average weekly hospitalization rate and mortality during the Flu Season (October to May). Conclusion As the majority of influenza-associated hospitalizations and deaths are in adults 65 years and older, a combination policy targeting higher vaccine effectiveness for this age group in the short term would be the most efficacious. Disclosures All Authors: No reported disclosures.