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Seasonal influenza epidemics result in high levels of healthcare utilization. Vaccination is an effective strategy to reduce the influenza-related burden of disease. However, reporting vaccine effectiveness does not convey the population impacts of influenza vaccination. We aimed to calculate the burden of influenza-related hospitalizations and emergency department (ED) attendance averted by influenza vaccination in Victoria, Australia, from 2017 to 2019, and associated economic savings. We applied a compartmental model to hospitalizations and ED attendances with influenza-specific, and pneumonia and influenza (P&I) with the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM) diagnostic codes of J09-J11 and J09-J18, respectively. We estimated an annual average of 7657 (120 per 100000 population) hospitalizations and 20560 (322 per 100000 population) ED attendances over the study period, associated with A$85 million hospital expenditure. We estimated that influenza vaccination averted an annual average of 1182 [range: 556 - 2277] hospitalizations and 3286 [range: 1554 - 6257] ED attendances and reduced the demand for healthcare services at the influenza season peak. This equated to approximately A13 [range: A6 - A25] million of savings over the study period. Calculating the burden averted is feasible in Australia and auseful approach to demonstrate the health and economic benefits of influenza vaccination.

BACKGROUND: This report summarizes the discussions and conclusions from the Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned from the COVID-19 Pandemic meeting, which took place in Seattle, USA, from March 1, 2023, to March 3, 2023. CONCLUSIONS: Discussions around influenza virus correlates of protection and their use continued from where the discussion had been left off in 2019. While there was not much progress in the influenza field itself, many lessons learned during the coronavirus disease 2019 (COVID-19) pandemic, especially the importance of mucosal immunity, were discussed and can directly be applied to influenza correlates of protection.

Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.

BACKGROUND: Co-administration of inactivated influenza vaccine (IIV) and SARS-CoV-2 vaccine may impact SARS-CoV-2 vaccine induced humoral immune responses. We aimed to compare IIV and SARS-CoV-2 vaccine induced cellular and humoral immune responses in those receiving concomitant vaccination to those receiving these vaccines separately. METHODS: We conducted a cohort study between 29th September 2021 and 5th August 2022 in healthcare workers who worked at the local NHS trust and in the surrounding area that were vaccinated with a mRNA SARS-CoV-2 booster and cell-based IIV. We measured haemagglutination inhibition assay (HAI) titres, SARS-CoV-2 anti-spike antibody and SARS-CoV-2 ELISpot count pre-vaccination, 1-month and 6-months post-vaccination and evaluated differences by vaccine strategy. FINDINGS: We recruited 420 participants, 234/420 (56%) were vaccinated concomitantly and 186/420 (44%) separately. The 1-month post-vaccination mean fold rise (MFR) in SARS-CoV-2 anti-spike antibodies was lower in those vaccinated concomitantly compared to separately (MFR [95% confidence interval (CI)] 9.7 [8.3, 11.4] vs 12.8 [10.3, 15.9], p = 0.04). After adjustment for age and sex, the adjusted geometric mean ratio (aGMR) remained lower for those vaccinated concomitantly compared to separately (aGMR [95% CI] 0.80 [0.70, 0.92], p = 0.001). At 6-months post-vaccination, we found no statistically significant difference in SARS-CoV-2 anti-spike antibody titres (aGMR [95% CI] 1.09 [0.87, 1.35], p = 0.45). We found no statistically significant correlation between vaccine strategy with SARS-CoV-2 ELISpot count and influenza HAI titres at 1-month and 6-months post-vaccination. INTERPRETATION: Our study found that concomitant vaccination with SARS-CoV-2 and IIV has no statistically significant impacts on long-term immunogenicity. Further research is required to understand the underlying mechanisms and assess the clinical significance of reduced anti-spike antibodies in those vaccinated concomitantly. FUNDING: Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

BACKGROUND: The effect of vaccination on the epigenome remains poorly characterized. In previous research, we identified an association between seroprotection against influenza and DNA methylation at sites associated with the RIG-1 signaling pathway, which recognizes viral double-stranded RNA and leads to a type I interferon response. However, these studies did not fully account for confounding factors including age, gender, and BMI, along with changes in cell-type composition. RESULTS: Here, we studied the influenza vaccine response in a longitudinal cohort vaccinated over two consecutive years (2019-2020 and 2020-2021), using peripheral blood mononuclear cells and a targeted DNA methylation approach. To address the effects of multiple factors on the epigenome, we designed a multivariate multiple regression model that included seroprotection levels as quantified by the hemagglutination-inhibition (HAI) assay test. CONCLUSIONS: Our findings indicate that 179 methylation sites can be combined as potential signatures to predict seroprotection. These sites were not only enriched for genes involved in the regulation of the RIG-I signaling pathway, as found previously, but also enriched for other genes associated with innate immunity to viruses and the transcription factor binding sites of BRD4, which is known to impact T cell memory. We propose a model to suggest that the RIG-I pathway and BRD4 could potentially be modulated to improve immunization strategies.

The M2 proton channel aids in the exit of mature influenza viral particles from the host plasma membrane through its ability to stabilize regions of high negative Gaussian curvature (NGC) that occur at the neck of budding virions. The channels are homo-tetramers that contain a cytoplasm-facing amphipathic helix (AH) that is necessary and sufficient for NGC generation; however, constructs containing the transmembrane spanning helix, which facilitates tetramerization, exhibit enhanced curvature generation. Here, we used all-atom molecular dynamics (MD) simulations to explore the conformational dynamics of M2 channels in lipid bilayers revealing that the AH is dynamic, quickly breaking the fourfold symmetry observed in most structures. Next, we carried out MD simulations with the protein restrained in four- and twofold symmetric conformations to determine the impact on the membrane shape. While each pattern was distinct, all configurations induced pronounced curvature in the outer leaflet, while conversely, the inner leaflets showed minimal curvature and significant lipid tilt around the AHs. The MD-generated profiles at the protein-membrane interface were then extracted and used as boundary conditions in a continuum elastic membrane model to calculate the membrane-bending energy of each conformation embedded in different membrane surfaces characteristic of a budding virus. The calculations show that all three M2 conformations are stabilized in inward-budding, concave spherical caps and destabilized in outward-budding, convex spherical caps, the latter reminiscent of a budding virus. One of the C2-broken symmetry conformations is stabilized by 4 kT in NGC surfaces with the minimum energy conformation occurring at a curvature corresponding to 33 nm radii. In total, our work provides atomistic insight into the curvature sensing capabilities of M2 channels and how enrichment in the nascent viral particle depends on protein shape and membrane geometry.

The aim of this project was to increase willingness to receive the influenza vaccine to the optimal rate of ≥ 70%. Low acuity adult patients who visited an Emergency Department (ED) were assessed regarding their willingness to receive the influenza vaccine before and after an educational intervention that included a provider recommendation and an educational handout. A total of seventy-six patients (n = 76) were assessed. Patients willingness to receive the influenza vaccine rose from 29% pre-intervention to 72% post-intervention without disrupting the clinical flow in a busy ED. Similar vaccine educational strategies can be applied to influenza and other vaccines in EDs  to increase vaccination willingness in patients, including those who use the ED as a primary point of contact for healthcare, decreasing the burden of influenza illness in the community.

Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet, the mechanisms are only partially understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a diet-induced obese ferret model and tools to demonstrate that, like humans, obesity resulted in notable changes to the lung microenvironment, leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for a longer period, making them more likely to transmit to contacts. These data suggest that the obese ferret model may be crucial to understanding obesitys impact on influenza disease severity and community transmission and a key tool for therapeutic and intervention development for this high-risk population.

ImportanceIncreasing influenza vaccination rates is a public health priority. One method recommended by the US Centers for Disease Control and Prevention and others is for health systems to send reminders nudging patients to be vaccinated.ObjectiveTo evaluate and compare the effect of electronic health record (EHR)-based patient portal reminders vs text message reminders on influenza vaccination rates across a health system.Design, setting, and participantsThis 3-arm randomized clinical trial was conducted from September 7, 2022, to April 30, 2023, among primary care patients within the University of California, Los Angeles (UCLA) health system.InterventionsArm 1 received standard of care. The health system sent monthly reminder messages to patients due for an influenza vaccine by portal (arm 2) or text (arm 3). Arm 2 had a 2 × 2 nested design, with fixed vs responsive monthly reminders and preappointment vs no preappointment reminders. Arm 3 had 1 × 2 design, with preappointment vs no preappointment reminders. Preappointment reminders for eligible patients were sent 24 and 48 hours before scheduled primary care visits. Fixed reminders (in October, November, and December) involved identical messages via portal or text. Responsive portal reminders involved a September message asking patients about their plans for vaccination, with a follow-up reminder if the response was affirmative but the patient was not yet vaccinated.Main outcomes and measuresThe primary outcome was influenza vaccination by April 30, 2023, obtained from the UCLA EHR, including vaccination from pharmacies and other sources.ResultsA total of 262 085 patients (mean [SD] age, 45.1 [20.7] years; 237 404 [90.6%] adults; 24 681 [9.4%] children; 149 349 [57.0%] women) in 79 primary care practices were included (87 257 in arm 1, 87 478 in arm 2, and 87 350 in arm 3). At the entire primary care population level, none of the interventions improved influenza vaccination rates. All groups had rates of approximately 47%. There was no statistical or clinically significant improvement following portal vs text, preappointment reminders vs no preappointment reminders (portal and text reminders combined), or responsive vs fixed monthly portal reminders.Conclusions and relevanceAt the population level, neither portal nor text reminders for influenza vaccination were effective. Given that vaccine hesitancy may be a major reason for the lack of impact of portal or text reminders, more intensive interventions by health systems are needed to raise influenza vaccination coverage levels.Trial registrationClinicalTrials.gov Identifier: NCT05525494.

BACKGROUND: Influenza vaccine viruses grown in eggs may acquire egg-adaptive mutations that may reduce antigenic similarity between vaccine and circulating influenza viruses and decrease vaccine effectiveness. We compared cell- and egg-based quadrivalent influenza vaccines (QIVc and QIVe, respectively) for preventing test-confirmed influenza over 3 US influenza seasons (2017-2020). METHODS: Using a retrospective test-negative design, we estimated the relative vaccine effectiveness (rVE) of QIVc vs QIVe among individuals aged 4 to 64 years who had an acute respiratory or febrile illness and were tested for influenza in routine outpatient care. Exposure, outcome, and covariate data were obtained from electronic health records linked to pharmacy and medical claims. Season-specific rVE was estimated by comparing the odds of testing positive for influenza among QIVc vs QIVe recipients. Models were adjusted for age, sex, geographic region, influenza test date, and additional unbalanced covariates. A doubly robust approach was used combining inverse probability of treatment weights with multivariable regression. RESULTS: The study included 31 824, 33 388, and 34 398 patients in the 2017-2018, 2018-2019, and 2019-2020 seasons, respectively; ∼10% received QIVc and ∼90% received QIVe. QIVc demonstrated superior effectiveness vs QIVe in prevention of test-confirmed influenza: rVEs were 14.8% (95% CI, 7.0%-22.0%) in 2017-2018, 12.5% (95% CI, 4.7%-19.6%) in 2018-2019, and 10.0% (95% CI, 2.7%-16.7%) in 2019-2020. CONCLUSIONS: This study demonstrated consistently superior effectiveness of QIVc vs QIVe in preventing test-confirmed influenza over 3 seasons characterized by different circulating viruses and degrees of egg adaptation.

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs. We reported recently that 2 d after immunization with live-attenuated VSR-disabled NoV (NoVΔB2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1-/- mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi-based protective immunity activated by NoVΔB2 immunization. We show that immunization of both neonatal and adult Rag1-/- mice with live but not killed NoVΔB2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoVΔB2-induced protective antiviral immunity is virus-specific and remains effective in adult Rag1-/- mice 42 and 90 d after a single-shot immunization. We conclude that immunization with the live-attenuated VSR-disabled RNA virus vaccine activates rapid and long-lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells. Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity-compromised individuals.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Improved vaccines can have substantial clinical and population impact, particularly when the effectiveness of standard vaccines is low, and burden is high.

BACKGROUND: Following the first locally transmitted case in Sukhbaatar soum, Selenge Province, we aimed to investigate the ultimate scale of the epidemic in the scenario of uninterrupted transmission. METHODS: This was a prospective case study following the locally modified WHO FFX cases generic protocol. A rapid response team collected data from November 14 to 29, 2020. We created a stochastic process to draw many transmission chains from this greater distribution to better understand and make inferences regarding the outbreak under investigation. RESULTS: The majority of the cases involved household transmissions (35, 52.2%), work transmissions (20, 29.9%), index (5, 7.5%), same apartment transmissions (2, 3.0%), school transmissions (2, 3.0%), and random contacts between individuals transmissions (1, 1.5%). The posterior means of the basic reproduction number of both the asymptomatic cases R 0 Asy $$ {R}_0^{Asy} $$ and the presymptomatic cases R 0 Pre $$ {R}_0^{Pre} $$ (1.35 [95% CrI 0.88-1.86] and 1.29 [95% CrI 0.67-2.10], respectively) were lower than that of the symptomatic cases (2.00 [95% Crl 1.38-2.76]). CONCLUSION: Our study highlights the heterogeneity of COVID-19 transmission across different symptom statuses and underscores the importance of early identification and isolation of symptomatic cases in disease control. Our approach, which combines detailed contact tracing data with advanced statistical methods, can be applied to other infectious diseases, facilitating a more nuanced understanding of disease transmission dynamics.

Birth-death models play a key role in phylodynamic analysis for their interpretation in terms of key epidemiological parameters. In particular, models with piecewise-constant rates varying at different epochs in time, to which we refer as episodic birth-death-sampling (EBDS) models, are valuable for their reflection of changing transmission dynamics over time. A challenge, however, that persists with current time-varying model inference procedures is their lack of computational efficiency. This limitation hinders the full utilization of these models in large-scale phylodynamic analyses, especially when dealing with high-dimensional parameter vectors that exhibit strong correlations. We present here a linear-time algorithm to compute the gradient of the birth-death model sampling density with respect to all time-varying parameters, and we implement this algorithm within a gradient-based Hamiltonian Monte Carlo (HMC) sampler to alleviate the computational burden of conducting inference under a wide variety of structures of, as well as priors for, EBDS processes. We assess this approach using three different real world data examples, including the HIV epidemic in Odesa, Ukraine, seasonal influenza A/H3N2 virus dynamics in New York state, America, and Ebola outbreak in West Africa. HMC sampling exhibits a substantial efficiency boost, delivering a 10- to 200-fold increase in minimum effective sample size per unit-time, in comparison to a Metropolis-Hastings-based approach. Additionally, we show the robustness of our implementation in both allowing for flexible prior choices and in modeling the transmission dynamics of various pathogens by accurately capturing the changing trend of viral effective reproductive number.

Vaccinating patients receiving dialysis may prevent morbidity and mortality in this vulnerable population. The National Forum of End-Stage Renal Disease Networks (the Forum) published a revised vaccination toolkit in 2021 to update evidence and recommendations on vaccination for patients receiving dialysis. Significant changes in the last 10 years include more data supporting the use of a high-dose influenza vaccine, the introduction of the Heplisav-B vaccine for hepatitis B, and changes in pneumococcal vaccines, including the approval of the PCV15 and PCV20 to replace the PCV13 and PPSV23 vaccines. Additional key items include the introduction of vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19), and a new vaccine to prevent respiratory syncytial virus disease. Historically, influenza and pneumococcal vaccinations were routinely administered by dialysis facilities, and because of possible risks of hematogenous spread of hepatitis B, dialysis providers often have detailed hepatitis B vaccine protocols. In March 2021, COVID-19 vaccines were made available for dialysis facilities to administer, although with the end of the public health emergency, vaccine policies by dialysis facilities against COVID-19 remains uncertain. The respiratory syncytial virus vaccine was authorized in 2023, and how dialysis facilities will approach this vaccine also remains uncertain. This review summarizes the Forums vaccination toolkit and discusses the role of the dialysis facility in vaccinating patients to reduce the risk of severe infections.

Vital to the treatment of influenza is the use of antivirals such as Oseltamivir (Tamiflu) and Zanamivir (Relenza); however, antiviral resistance is becoming an increasing problem for these therapeutics. The RNA-dependent RNA polymerase acidic N-terminal (PAN) endonuclease, a critical component of influenza viral replication machinery, is an antiviral target that was recently validated with the approval of Baloxavir Marboxil (BXM). Despite its clinical success, BXM has demonstrated susceptibility to resistance mutations, specifically the I38T, E23K, and A36 V mutants of PAN. To better understand the effects of these mutations on BXM resistance and improve the design of more robust therapeutics, this study examines key differences in protein-inhibitor interactions with two inhibitors and the I38T, E23K, and A36 V mutants. Differences in inhibitor binding were evaluated by measuring changes in binding to PAN using two biophysical methods. The binding mode of two distinct inhibitors was determined crystallographically with both wild-type and mutant forms of PAN. Collectively, these studies give some insight into the mechanism of antiviral resistance of these mutants.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

Influenza virus infection alters the promoter DNA methylation of key immune response-related genes, including type-1 interferons and proinflammatory cytokines. However, less is known about the effect of the influenza vaccine on the epigenome. We utilized a targeted DNA methylation approach to study the longitudinal effects (day 0 pre-vaccination and day 28 post-vaccination) on influenza vaccination responses in peripheral blood mononuclear cells. We found that baseline, pre-vaccination methylation profiles are associated with pre-existing, protective serological immunity. Additionally, we identified 481 sites that were differentially methylated between baseline and day 28 post-vaccination. These were enriched for genes involved in the regulation of the RIG-I signaling pathway, an important regulator of viral responses. Our results suggest that DNA methylation changes to components of the RIG-I pathway are associated with vaccine effectiveness. Therefore, immunization strategies that target this pathway may improve serological responses to influenza vaccination.

In humans, acute and chronic respiratory infections caused by viruses are associated with considerable morbidity and mortality. Respiratory viruses infect airway epithelial cells and induce oxidative stress, yet the exact pathogenesis remains unclear. Oxidative stress activates the transcription factor NRF2, which plays a key role in alleviating redox-induced cellular injury. The transcriptional activation of NRF2 has been reported to affect both viral replication and associated inflammation pathways. There is complex bidirectional crosstalk between virus replication and the NRF2 pathway because virus replication directly or indirectly regulates NRF2 expression, and NRF2 activation can reversely hamper viral replication and viral spread across cells and tissues. In this review, we discuss the complex role of the NRF2 pathway in the regulation of the pathogenesis of the main respiratory viruses, including coronaviruses, influenza viruses, respiratory syncytial virus (RSV), and rhinoviruses. We also summarize the scientific evidence regarding the effects of the known NRF2 agonists that can be utilized to alter the NRF2 pathway.

Influenza remains a serious issue for public health and it's urgent to discover more effected drugs against influenza virus. Rhamnocitrin, as a flavonoid, its effect on influenza virus infection remains poorly explored. In this study, rhamnocitrin showed antiviral effect and anti-apoptosis on influenza virus A/Aichi/2/1968 (H3N2) in MDCK cells and A549 cells. In addition, molecular docking revealed that rhamnocitrin have good binding activity with the target proteins cGAS and STING, molecular dynamic simulation and surface plasmon resonance showed that rhamnocitrin could form a stable complex with the above proteins. Moreover, the qPCR and western blot assays further verified that rhamnocitrin could reduce type I IFN and proinflammatory cytokines production by inhibiting the cGAS/STING pathway. Taken together, the results suggest that rhamnocitrin could be a potential anti-viral agent against influenza. [ABSTRACT FROM AUTHOR]

The avian influenza is a serious infection caused by influenza virus that is native to birds. Avian influenza remains a global challenge due to high transmission and mortality rates. The highly pathogenic strain of H5N1 resulted in significant outbreaks and deaths globally since the late 1800s. The most recent outbreaks in wild birds, domestic birds, and cows with some genetic variations and mutations among H5N1 strains has raised major concerns about potential transmission and public health risks. Symptoms range from asymptomatic to mild flu‐like illness to severe illness that requires hospitalization. There are multiple vaccines in development for humans to protect against avian influenza, specifically the H5N1 virus. This includes a cell‐based vaccine approved by the FDA for people aged 6 months and older who are at higher risk of exposure to the H5N1 virus called Audenz. Chemoprophylaxis against avian influenza following a suspected exposure should be started as soon as possible or no later than 48 h, and it is recommended to be continued for 7 days. The majority of avian influenza viruses are susceptible to neuraminidase inhibitors and cap‐dependent endonuclease inhibitor. Neuraminidase inhibitors are the mainstay of the avian influenza treatment and includes oseltamivir, peramivir, and zanamivir. Baloxavir marboxil is a cap‐dependent endonuclease inhibitor. This clinical review aims to highlight the background, epidemiology, clinical presentation, complications and current treatment and prevention strategies for avian influenza H5N1. [ABSTRACT FROM AUTHOR]

Background and Purpose: Fibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral–fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza‐induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral‐mediated fibrotic remodelling. Experimental Approach: A retrospective analysis of TriNetX data sets was conducted. Serum from healthy controls and influenza A virus (IAV)‐infected patients was analysed. An inhibitor of PDIA3, punicalagin, and a neutralizing antibody for SPP1 were administered in mice. Macrophage cells treated with macrophage colony‐stimulating factor (M‐CSF) were used as a cell culture model. Key Results: The TriNetX data set showed an increase in lung fibrosis and decline in lung function in flu‐infected acute respiratory distress syndrome (ARDS) patients compared with non‐ARDS patients. Serum samples revealed a significant increase in SPP1 and PDIA3 in influenza‐infected patients. Lung PDIA3 and SPP1 expression increased following viral infection in mouse models. Punicalagin administration 2 weeks after IAV infection in mice caused a significant decrease in lung fibrosis and improved oxygen saturation. Administration of neutralizing SPP1 antibody decreased lung fibrosis. Inhibition of PDIA3 decreased SPP1secretion from macrophages, in association with diminished disulfide bonds in SPP1. Conclusion and Implications: The PDIA3–SPP1 axis promotes post‐influenza lung fibrosis in mice and that pharmacological inhibition of PDIA3 or SPP1 can treat virus‐induced lung fibrotic sequela. [ABSTRACT FROM AUTHOR]

While molecular testing is recommended for symptomatic patients suspected of having coronavirus disease 2019 (COVID-19), limited data are available examining real-world use of tests for severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the impact of SARS-CoV-2 testing on patient outcomes. In this retrospective cohort study using de-identified administrative claims data in the Optum Labs Data Warehouse, we identified 2 groups of patients with ≥1 outpatient claims with a procedure code for SARS-CoV-2 testing between January 2021 and September 2022. Group 1 had ≥1 claims with CPT code 0240U or 0241U ("Xpert Xpress") (N = 51,602); Group 2 had ≥1 claims for laboratory-based molecular testing (N = 317,192). Outcomes assessed on the identification date and through the 90-day follow-up included claims evidence of use of SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) tests, diagnosis of active COVID-19, influenza, or RSV, and use of treatments (antivirals for COVID-19, influenza, and RSV and other treatments for COVID-19 and RSV). Patients in Group 1 had fewer tests for SARS-CoV-2, influenza, or RSV (mean ± standard deviation 1.6±1.4 versus 2.6±2.6, standardized difference -0.45), faster time to diagnosis of COVID-19 (median 0 versus 4 days, standardized difference -0.27) or influenza (median 0 versus 5 days, standardized difference -0.74), and faster time to treatment of COVID-19, influenza, or RSV (median 1 versus 5 days, standardized difference 0.16) than patients in Group 2. In this nationwide real-world study of outpatient testing, use of point-of-care molecular multiplex SARS-CoV-2 testing resulted in fewer claims for SARS-CoV-2, influenza, and RSV tests, faster time to diagnosis, and faster time to treatment than laboratory-based molecular testing. [ABSTRACT FROM AUTHOR]

Pathogen encounter can result in epigenetic remodeling that shapes disease caused by heterologous pathogens. Here, we examined innate immune memory in the context of commonly circulating respiratory viruses. Single-cell analyses of airway-resident immune cells in a disease-relevant murine model of SARS-CoV-2 recovery revealed epigenetic reprogramming in alveolar macrophages following infection. Post-COVID-19 human monocytes exhibited similar epigenetic signatures. In airway-resident macrophages, past SARS-CoV-2 infection increased activity of type I interferon (IFN-I)-related transcription factors and epigenetic poising of antiviral genes. Viral pattern recognition and canonical IFN-I signaling were required for the establishment of this innate immune memory and augmented secondary antiviral responses. Antiviral innate immune memory mounted by airway-resident macrophages post-SARS-CoV-2 was necessary and sufficient to ameliorate secondary disease caused by influenza A virus and curtailed hyperinflammatory dysregulation and mortality. Our findings provide insights into antiviral innate immune memory in the airway that may facilitate the development of broadly effective therapeutic strategies. [Display omitted] • Airway-resident macrophages (AMF) establish durable epigenetic memory post SARS2 • Chromatin loci of ISGs retain increased accessibility and are decorated with H3K4me1 • AMFs hyper-induce ISGs upon secondary antiviral recall responses • Innate immune memory in AMF ameliorates secondary influenza A virus disease The therapeutic potential of antigen-independent innate immune memory (IIM) is of particular relevance in the context of respiratory viruses with pandemic potential. Lercher et al. find that antiviral IIM in alveolar macrophages following SARS-CoV-2 infection ameliorates disease caused by a secondary unrelated pathogen, influenza A virus. [ABSTRACT FROM AUTHOR]

We reviewed research on SARS-CoV-2 and influenza virus detection on surfaces, their persistence under various conditions, and response to disinfectants. Viral contamination in community and healthcare settings was analyzed, emphasizing survival on surfaces influenced by temperature, pH, and material. Findings showed higher concentrations enhance survivability at room temperature, whereas stability increases at 4°C. Both viruses decline in low pH and high heat, with influenza affected by salinity. On various material surfaces, SARS-CoV-2 and influenza viruses demonstrate considerable variations in survival durations, and SARS-CoV-2 is more stable than influenza virus. On the skin, both virus types can persist for ≥2 h. Next, we delineated the virucidal efficacy of disinfectants against SARS-CoV-2 and influenza viruses. In daily life, exposure to ethanol (70%), isopropanol (70%), bleach (10%), or hydrogen peroxide (1–3%) for 15–30 min can effectively inactive various SARS-CoV-2 variants. Povidone-iodine (1 mg/mL, 1 min) or cetylpyridinium chloride (0.1 mg/mL, 2 min) may be used to inactive different SARS-CoV-2 variants in the mouth. Chlorine disinfectants (500 mg/L) or ultraviolet light (222 nm) can effectively inhibit different SARS-CoV-2 variants in public spaces. In conclusion, our study provides a scientific basis and practical guidance for reduction of viral persistence (retention of infectivity) on surfaces and environmental cleanliness. [ABSTRACT FROM AUTHOR]

Rationale: The influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza-associated pulmonary aspergillosis (IAPA) or coronavirus disease (COVID-19)–associated pulmonary aspergillosis (CAPA) has yet to be explored. Objectives: To explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity, and outcome in severe influenza versus COVID-19 with or without aspergillosis. Methods: We performed a retrospective study in mechanically ventilated patients with influenza and COVID-19 with or without invasive aspergillosis in whom BAL for bacterial culture (with or without PCR) was obtained within 2 weeks after ICU admission. In addition, 16S rRNA gene sequencing data and viral and bacterial load of BAL samples from a subset of these patients, and of patients requiring noninvasive ventilation, were analyzed. We integrated 16S rRNA gene sequencing data with existing immune parameter datasets. Measurements and Main Results: Potential bacterial pathogens were detected in 20% (28/142) of patients with influenza and 37% (104/281) of patients with COVID-19, whereas aspergillosis was detected in 38% (54/142) of patients with influenza and 31% (86/281) of patients with COVID-19. A significant association between bacterial pathogens in BAL fluid and 90-day mortality was found only in patients with influenza, particularly patients with IAPA. Patients with COVID-19, but not patients with influenza, showed increased proinflammatory pulmonary cytokine responses to bacterial pathogens. Conclusions: Aspergillosis is more frequently detected in the lungs of patients with severe influenza than bacterial pathogens. Detection of bacterial pathogens associates with worse outcome in patients with influenza, particularly in those with IAPA, but not in patients with COVID-19. The immunological dynamics of tripartite viral–fungal–bacterial interactions deserve further investigation. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory infection (SARI) is a major cause for hospital admission and associated with high mortality among children worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses and respiratory syncytial virus (RSV) are the most frequently identified pathogens in children with SARI. The duration of care can be affected by the type of infection and patient characteristics. Therefore, the objective of this study was to identify factors affecting the length of hospitalization in children infected with SARS-CoV-2, influenza A and RSV. Methods: We collected data on 713 children with SARI from the medical databases of a university hospital in Hungary. To examine whether there is a difference in the length of hospitalization in children with the SARI Kruskal-Wallis test was performed. To determine the factors that may have an impact on the duration of care a multiple logistic regression analysis was executed. Results: Our results showed that among RSV infected patients the proportions of children requiring intensive care (8.94%), mechanical ventilation (8.94%) and oxygen therapy (13.01%) and suffering from pneumonia (29.27%) were larger than among cases with SARS-CoV-2 and influenza A infection. Considering the age distribution and the duration of care in children with SARI, cases with RSV were significantly younger (p < 0.001) and stayed longer in the hospital (median: 5 days, IQR: 4–7 days, p < 0.001) than those with SARS-CoV-2 and influenza A virus. Multiple logistic regression analysis showed that RSV infection (adjusted odds ratio (aOR): 3.25, 95% confidence interval (CI): 1.43–7.38; p = 0.005), pneumonia (aOR: 3.65, 95% CI: 2.14–6.24; p < 0.001), mechanical ventilation or oxygen therapy (aOR: 3.23, 95% CI: 1.29–8.11; p = 0.012) and underlying illnesses (aOR: 2.39, 95% CI: 1.35–4.23; p = 0.003) significantly increased the odds of hospitalization for more than 4 days. Conclusions: Our research showed that of the viruses causing SARI, RSV had the greatest clinical relevance, contributing to hospital stays of more than 4 days in a large share of paediatric patients below 1 year of age. Our results supply new information on children with SARI, and provide evidence for health policy makers to allocate additional resources to hospitals during SARI epidemics. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion Influenza outbreaks of varying size occur every year, but during the COVID‐19 pandemic, many countries experienced influenza at lower levels. However, following the relaxation of COVID‐19 prevention measures in 2022, the incidence of influenza began to increase gradually. Thus, this study compared the occurrence of influenza from week 36 of 2017, before the COVID‐19 outbreak, until 2023.The analysis was conducted using influenza‐like illness occurrence data available from the Korea Disease Control and Prevention Agency infectious disease website. Additionally, to examine the changes in COVID‐19 and influenza occurrence during the pandemic, COVID‐19 incidence data from 20 January 2020 to 31 August 2023 were obtained from the KDCA Coronavirus Disease 19 homepage.During the COVID‐19 pandemic, which corresponds to the 2020/2021 and 2021/2022 influenza seasons, there was no seasonal influenza epidemic, and the incidence rates were below the usual outbreak levels. However, in the 2022/2023 season, when the spread of COVID‐19 had eased, a seasonal pattern similar to that observed before the COVID‐19 pandemic was noted. Furthermore, correlation analysis between the rates of influenza‐like illness and COVID‐19 incidence showed no significant correlation during the entire period. However, a significant correlation emerged in 2023 (r = 0.393, p <0.05). These results suggest that influenza was suppressed during the COVID‐19 pandemic but returned to typical seasonal patterns after the COVID‐19 prevention policies were eased.The positive correlation observed between the incidences of COVID‐19 and influenza in 2023 indicates that COVID‐19, no longer a novel pandemic‐causing infectious disease, may have transitioned to an endemic pattern similar to seasonal influenza. [ABSTRACT FROM AUTHOR]

Seasonal and pandemic influenza infection present a potential threat to patients with antibody deficiency. The acceptance and effect of the current recommendation for annual vaccination against influenza for patients with antibody deficiency is not well investigated and due to antigenic drift or shift the protective capacity of regular IgG replacement therapy (IgRT) is considered low. This narrative review considers the effect of influenza vaccination in immunodeficient patients and discusses available information on the effect of immunoglobulin products on seasonal influenza infectivity and severity in antibody deficiency patients receiving IgRT. The humoral immune response to seasonal influenza vaccination is reduced in patients with antibody immune deficiency. However, there is no evidence that the proportion of patients with primary antibody deficiency who develop influenza illness, and the severity of such illness, is increased when compared with the general population. The IgRT that patients receive has been shown to contain neutralizing antibodies as a consequence of past flu infections against both the hemagglutinin and neuraminidase surface proteins and other viral internal proteins of different influenza A virus strains. Studies have demonstrated not only significant levels of specific but also cross-reactive antibodies against seasonal influenza virus strains. Thus, despite the yearly changes in influenza viral antigenicity that occur, IgRT could potentially contribute to the protection of patients against seasonal influenza. Currently, only limited clinical data are available confirming a preventative effect of IgRT with respect to seasonal influenza infection. In conclusion, there is some evidence that IgRT could contribute to protection against seasonal influenza in patients with antibody-related immunodeficiency. However, additional clinical data are needed to confirm the extent and relevance of this protection and identify the main responsible virus targets of that protection. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) was a more severe illness than seasonal influenza in hospitalised cohorts during the early phase of the pandemic. This study's aim was to determine if COVID-19 severity, relative to seasonal influenza, evolved across subsequent disease waves. Retrospective population-based cohort study. COVID-19 hospital episodes and seasonal influenza hospital episodes were identified using relevant International Classification of Disease (ICD-10) codes from the Irish national hospitalisation dataset. Descriptive comparative analysis of each group was carried out using Pearson's Chi-squared tests. Length of stay (LOS), intensive care unit (ICU) admission and in-hospital mortality were measured and compared using logistic regression analysis. Compared to influenza episodes, COVID-19 episodes for all ages and all waves combined, had a longer mean LOS (15.8 days, vs 11.4 days, P < 0.001); were more likely to receive ICU care (OR 1.24 95% CI 1.15–1.33, P < 0.001) and were more likely to die in hospital (OR 2.61, 95% CI 2.36-2-88). Despite the reduction in the proportion of patients with an intensive care unit (ICU) stay and dying in hospital in Wave 5 compared to the previous waves, the risk of having an ICU admission or dying in hospital remained higher in patients with COVID-19 in Wave 5 compared to those with influenza diagnosis. While the severity of COVID-19 has reduced with successive pandemic waves, it remains a more severe disease than influenza. Despite changes in strain, population immunity, vaccination and treatment, policymakers and the public must continue to approach COVID-19 as more than 'just a bad flu'. [ABSTRACT FROM AUTHOR]

Objective: To promote influenza vaccine acceptance among community college students during the Fall 2020 semester to reduce the incidence of a "twin-demic" occurring of influenza and COVID-19. Participants: A convenience sample of 185 students enrolled in an entry level health course. Methods: Non-experimental cross-sectional design that used a self-paced, online teaching intervention. Qualitative data in the form of online discussion board posts were collected and analyzed assessing attitudes, normative references, and knowledge. Results: High rates of favorable attitudes toward influenza vaccine, evidence of subjective normative references toward science-based information, and an increase in participant knowledge. Conclusions: An online teaching intervention can be effective in changing attitudes, referencing subjective norms related to scientific information, and increasing knowledge. [ABSTRACT FROM AUTHOR]

The gut microbiota metabolizes flavonoids, amino acids, dietary fiber, and other components of foods to produce a variety of gut microbiota-derived metabolites. Flavonoids are the largest group of polyphenols, and approximately 7000 flavonoids have been identified. A variety of phenolic acids are produced from flavonoids and amino acids through metabolic processes by the gut microbiota. Furthermore, these phenolic acids are easily absorbed. Phenolic acids generally represent phenolic compounds with one carboxylic acid group. Gut microbiota-derived phenolic acids have antiviral effects against several viruses, such as SARS-CoV-2 and influenza. Furthermore, phenolic acids influence the immune system by inhibiting the secretion of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α. In the nervous systems, phenolic acids may have protective effects against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, phenolic acids can improve levels of blood glucose, cholesterols, and triglycerides. Phenolic acids also improve cardiovascular functions, such as blood pressure and atherosclerotic lesions. This review focuses on the current knowledge of the effects of phenolic acids produced from food-derived flavonoids and amino acids by the gut microbiota on health and disease. [ABSTRACT FROM AUTHOR]

Introduction: In the context of adverse in utero environments, the fetal brain might be preserved at the expense of other tissues. This trade‐off, brain sparing, has not been studied in the context of maternal infection. We investigated cases of maternal syphilis in the early 20th century and influenza during the 1918–1920 pandemic, in the Swiss city of Lausanne, a relatively high‐income setting. We tested the brain sparing hypothesis, that head circumference is protected at the expense of birth weight. Methods: A total of 8530 individual birth records from 1911 to 1922 from the University Maternity Hospital of Lausanne were used. We fitted generalized linear and additive linear models to explain how neonatal size varies under disease exposure. Results: Influenza reduced head circumference and birth weight among livebirths similarly, by −0.11 and −0.14 standard deviation (SD) units respectively. Conversely, for syphilis‐exposed infants, head circumference was affected more than birth weight (−0.61 SD vs. −0.46 SD). Stillborn infants exposed to syphilis experienced a much greater reduction in head circumference (−1.92 SD) than liveborn infants. After adjustment for gestational age, these findings persisted in the case of influenza, but the effects of syphilis were reduced. Furthermore, half of syphilis‐exposed infants were born before term, suggesting that lower infant size was partly mediated by shorter gestation. Nevertheless, head circumference among stillbirths exposed to syphilis was still substantially reduced, even after adjustment for gestational age (−1.26 SD). Conclusion: Our findings do not support the brain sparing hypothesis. Moreover, the substantial reduction in head circumference among syphilis‐exposed fetuses might help explain why a quarter of them were stillborn. [ABSTRACT FROM AUTHOR]

The article examines the current status of H5N1 avian influenza, emphasizing its low risk to humans despite widespread animal infections. Topics discussed include the virus's spread among wild and domestic animals, potential for mammalian transmission, and the importance of monitoring and managing risks to prevent human infection.

A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated that antibiotic treatment during influenza infection caused a fungal dysbiosis that drove lung eosinophilia and impaired MRSA clearance. Finally, we evaluated 3 cohorts of hospitalized patients and found that eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs, thereby increasing the risk of developing a secondary bacterial infection. [ABSTRACT FROM AUTHOR]

Background Aim Design Results Conclusion Routine immunisation for influenza and pneumococcal disease has the potential to reduce morbidity and mortality in patients with cancer.This scoping review aims to determine barriers to influenza and pneumococcal vaccinations from the perspective of patients with cancer and to discuss the potential role of the pharmacist in impacting these barriers.A systematic search of seven databases, including MEDLINE (Ovid), Cochrane Library, Informit (health), PubMed, and CINAHL (complete), from database inception to 6 June 2023 was conducted. Search terms included: 'cancer', 'vaccination', 'influenza', 'pneumococcal', and 'barrier'. Articles published in English that describe barriers to receiving vaccinations from the perspectives of patients with cancers were included. Barriers were thematically analysed.Twenty‐five articles met the inclusion criteria. Barriers identified in the literature were analysed into three key themes: healthcare professionals, patients, and healthcare system barriers. A key healthcare professional barrier was lack of recommendations from the treating oncologist or haematologist. Patient barriers included lack of information about the indication for vaccination as part of patients' cancer treatment and fear of side effects. Access to vaccination services was reported as a healthcare system barrier.This scoping review highlights the significant barriers to influenza and pneumococcal vaccination according to patients with cancer. Healthcare professionals, patients, and health systems were identified as key barriers. Enablers to improve vaccination rates include patient education, increased healthcare professional vaccine recommendations, and improved access. Although pharmacists have a potential role to play in addressing these barriers, the feasibility and impact of their involvement requires further research. [ABSTRACT FROM AUTHOR]

Highly pathogenic avian influenza A(H5N1) detected in dairy cows raises concerns about milk safety. The effects of pasteurization-like temperatures on influenza viruses in retail and unpasteurized milk revealed virus resilience under certain conditions. Although pasteurization contributes to viral inactivation, influenza A virus, regardless of strain, displayed remarkable stability in pasteurized milk. [ABSTRACT FROM AUTHOR]

In Kenya, influenza virus circulates year-round, raising questions about optimum strategies for vaccination. Given national interest in introducing influenza vaccination for young children 6-23 months of age, we modeled total influenza-associated illnesses (inclusive of hospitalizations, outpatient illnesses, and non-medically attended illnesses) averted by multiple potential vaccination strategies: yearround versus seasonal-campaign vaccination, and vaccination starting in April (Southern Hemisphere influenza vaccine availability) versus October (Northern Hemisphere availability). We modeled average vaccine effectiveness of 50% and annual vaccination coverage of 60%. In the introduction year, year-round vaccination averted 6,410 total illnesses when introduced in October and 7,202 illnesses when introduced in April, whereas seasonal-campaign vaccination averted 10,236 (October) to 11,612 (April) illnesses. In the year after introduction, both strategies averted comparable numbers of illnesses (10,831-10,868 for year-round, 10,175-11,282 for campaign). Campaign-style vaccination would likely have a greater effect during initial pediatric influenza vaccine introduction in Kenya; however, either strategy could achieve similar longer-term effects. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls. Methods: We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission < 30 days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. Results: We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3 months) and COVID-19 (4 months) were younger than influenza (9.1 months) patients. Sixteen percent of patients had RSV within the first month of life. Most infants did not have comorbidities (74% RSV, 56% influenza, and 69% COVID-19). Forty-one percent of patients with RSV and influenza were coinfected vs. 27% COVID-19 (p = 0.04). Among RSV, hospitalization risk factors were prematurity (adjusted OR 3.11 [95% CI 1.66, 4.44]) and coinfection (2.03 [1.45, 2.85]). Risks for higher severity were maternal smoking (1.89 [1.07, 3.33]), prematurity (2.31 [1.59, 3.34]), chronic lung disease (2.20 [1.06, 4.58]), neurodevelopmental condition (4.28 [2.10, 8.73]), and coinfection (2.67 [2.09, 3.40]). Breastfeeding was protective against hospitalization (0.87 [0.80, 0.95]) and severity (0.81 [0.74, 0.88]), while complete vaccination schedule was protective against severity (0.51 [0.27, 0.97]). RSV had 2.47 (1.03, 5.96) higher risk of experiencing any severe outcome compared to influenza and did not show significant differences vs. COVID-19. Conclusions: RSV hospitalizations were more frequent and severe than influenza, while severity was comparable to the early pandemic COVID-19. Currently, both influenza and COVID-19 vaccines are included in the maternal and childhood Spanish immunization schedule between the ages of 6 and 59 months. RSV monoclonal antibody is recommended for ≤ 6 months but a third of patients were aged 6–24 months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding. [ABSTRACT FROM AUTHOR]

Introduction: 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). Methods: 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. Results: 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 35–59 years (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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

To evaluate the relative effectiveness of high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) against recurrent hospitalizations and its potential variation in relation to influenza circulation. We did a post-hoc analysis of a pragmatic, open-label, randomized trial of QIV-HD versus QIV-SD performed during the 2021–2022 influenza season among adults aged 65–79 years. Participants were enrolled in October 2021–November, 2021 and followed for outcomes from 14 days postvaccination until 31 May, 2022. We investigated the following outcomes: Hospitalizations for pneumonia or influenza, respiratory hospitalizations, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations, and all-cause death. Outcomes were analysed as recurrent events. Cumulative numbers of events were assessed weekly. Cumulative relative effectiveness estimates were calculated and descriptively compared with influenza circulation. The trial is registered at Clinicaltrials.gov: NCT05048589. Among 12,477 randomly assigned participants, receiving QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza (10 vs. 33 events, incidence rate ratio [IRR] 0.30 [95% CI, 0.14–0.64]; p 0.002) and all-cause hospitalizations (647 vs. 742 events, IRR 0.87 [95% CI, 0.76–0.99]; p 0.032) compared with QIV-SD. Trends favouring QIV-HD were consistently observed over time including in the period before active influenza transmission; i.e. while the first week with a ≥10% influenza test positivity rate was calendar week 10, 2022, the first statistically significant reduction in hospitalizations for pneumonia or influenza was already observed by calendar week 3, 2022 (5 vs. 15 events, IRR 0.33 [95% CI, 0.11–0.94]; p 0.037). In a post-hoc analysis, QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza and all-cause hospitalizations compared with QIV-SD, with trends evident independent of influenza circulation levels. Our exploratory results correspond to a number needed to treat of 65 (95% CI 35–840) persons vaccinated with QIV-HD compared with QIV-SD to prevent one additional all-cause hospitalization per season. Further research is needed to confirm these hypothesis-generating findings. [ABSTRACT FROM AUTHOR]

Benign acute childhood myositis is a benign phenomenon often associated with influenza in children. The aim of this scoping review was to analyze the typical clinical picture and characteristics of benign acute childhood myositis patients. Furthermore, we aimed to analyze the epidemiology and viral findings. We performed a systematic scoping review. We searched PubMed, Scopus, Web of Science, and CINAHL databases in August 2023. We included observational studies that focused on children and reported at least 10 children. Our main outcome was to describe the typical clinical picture of benign acute childhood myositis patients. Furthermore, we aimed to report the typical laboratory findings and virus findings. A total of 211 studies were screened, and 22 studies were included in this review. The included studies were mainly from Europe (13 studies) and Asia (5 studies). Two studies were prospective, and the rest were retrospective. The mean age of the patients was 6.8 (CI 5.8–7.8) years. Benign acute childhood myositis appeared to be more prevalent among boys in all studies. The most prevalent symptoms were bilateral leg pain (pooled prevalence 92%), followed by fever (80%) and inability to walk (56%). Hospitalization rates varied between 4 and 100%, and the mean hospital stay was 3.6 (CI 3.3–3.9) days. Influenza B was the most common virus detected, followed by influenza A. Other reported viruses included herpes simplex, coxsackie-, enteroviruses, adeno-, respiratory syncytial, and parainfluenza viruses. All studies reported creatinine kinase levels, and the reported mean values varied between 100 and 4000 U/L, whereas only five studies reported C-reactive protein which was only slightly elevated. Conclusion: According to a systematic assessment of published literature, benign acute childhood myositis patients were typically school-aged children, presenting with bilateral leg pain, fever, and inability to walk. Influenza A and B were the most reported viruses, but multiple other viruses have been associated with benign acute childhood myositis. These patients have high creatinine kinase values, but their hospital stay was rather short. Overall, this review provides important information for clinicians on the characteristic presentation of benign acute childhood myositis, and these findings may help to better identify these patients and reduce unnecessary tests. What is known: • Benign acute childhood myositis has been mainly associated with influenza viruses, especially B influenza. • Typical patients have been reported to be under school-aged children, and boys have been reported to have a higher incidence. What is new: • Many non-influenza viruses were also associated with benign acute childhood myositis, such as herpes simplex, coxsackie-, entero-, adeno-, respiratory syncytial, and parainfluenza viruses. • Typical symptoms are bilateral calf pain, fever, and inability to walk and creatine kinase levels were reposted to be increased. [ABSTRACT FROM AUTHOR]

Background: Adults 65 years of age and older are at higher risk of influenza complications, such as hospitalization and death. As a result, seasonal influenza immunization is particularly important for this group. Objective: This supplemental statement provides an evidence summary on the preferential use of one or more of the age-appropriate influenza vaccines for adults 65 years of age and older, over other age-appropriate influenza vaccines. Methods: The National Advisory Committee on Immunization (NACI)’s Influenza Working Group undertook an overview of existing systematic reviews on the efficacy, effectiveness, safety and cost effectiveness of influenza vaccination in adults 65 years of age and older. Additionally, NACI’s evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings and apply an ethics, feasibility and acceptability lens to develop recommendations. Results: The evidence suggests that high-dose inactivated influenza vaccine (IIV-HD), adjuvanted inactivated influenza vaccine (IIV-Adj) and recombinant influenza vaccine (RIV) offer increased benefits for adults 65 years of age and older when compared to standard dose influenza vaccines. The IIV-HD had the most supporting evidence, followed by IIV-Adj and then RIV. Evidence comparing these enhanced vaccines was limited. Conclusion: Following a thorough review of the complete body of evidence, NACI recommends that IIV-HD, IIV-Adj or RIV should be offered over other influenza vaccines for adults 65 years of age and older. NACI also continues to strongly recommend the inclusion of adults 65 years of age and older among those for whom it is particularly important to receive influenza vaccination. [ABSTRACT FROM AUTHOR]

Background: The National Advisory Committee on Immunization (NACI) reviews the evolving evidence on influenza immunization and provides annual recommendations regarding the use of seasonal influenza vaccines. The NACI Statement on Seasonal Influenza Vaccine for 2024– 2025 updates the NACI recommendations from the previous year. Objective: To summarize the 2024–2025 NACI seasonal influenza vaccine recommendations and to highlight new and updated information. Methods: For the development of the Statement on Seasonal Influenza Vaccine for 2024–2025, the NACI Influenza Working Group applied the NACI evidence-based process to assess available evidence and formulate recommendations. These recommendations underwent a thorough evaluation and were approved by NACI based on the available evidence. Results: Key updates for the 2024–2025 influenza season include updated immunization recommendations reflecting changes in influenza epidemiology and revised guidance for vaccine administration during pregnancy and in older adults. Conclusion: The National Advisory Committee on Immunization recommends that any age-appropriate quadrivalent or trivalent influenza vaccine should be used for individuals six months of age and older who do not have contraindications or precautions. NACI reaffirms the importance of influenza vaccination with inactivated or recombinant influenza vaccines in pregnancy. Finally, NACI recommends that inactivated high-dose (IIV-HD), inactivated adjuvanted (IIV-Adj) or recombinant influenza vaccine (RIV) should be offered, when available, over other influenza vaccines for adults 65 years of age and older. [ABSTRACT FROM AUTHOR]

Background: Influenza is an acute respiratory illness caused by the influenza virus. There are 3 types of influenza virus A, B and C. Infection with the influenza virus exhibits broad immune responses and protection from re-infection by the same type of virus. The protective humoral immune response depends mainly on antibodies to the virus surface glycoprotein, hemagglutinin, and neuraminidase. Our study aims to reveal the characteristics of hemagglutinin reactive serum antibody responses in influenza patients in Suez Governorate. Methods: 160 cases were enrolled according to their clinical picture and symptoms onset not more than 10 days from the beginning of illness. Nasopharyngeal swabs were obtained from each case and tested for the influenza virus by rapid influenza antigen detection test. The proven influenza A samples were typed by real-time PCR. Each sample was mapped for their hemagglutinin (HA) antibodies rising titer by ELISA: group 1 HAs (H1, H5, H9) and group 2 HAs (H3 and H7). Results: 15 cases were diagnosed as influenza A with subtype H1N1. There was a rise in group 1HAs more than group 2 HAs when comparing the antibody titer of the 1st and 2nd serum samples. Group 1: H1 showed a 20-fold rise, H5 showed a 5-fold rise and H9 showed a 2-fold rise. Group 2: H3 and H9 showed a 5-fold rise. Conclusion: Following natural infection; influenza A(H1N1) pdm09 virus induces a strong anti-HA immune response. [ABSTRACT FROM AUTHOR]

In 1977, the Soviet Union (Union of Soviet Socialist Republics [USSR]) notified the World Health Organization (WHO) about an outbreak of H1N1 influenza, which later spread to many countries. The H1N1 strain of 1977 reappeared after being absent from the world for over 20 years. This pandemic simultaneously spread to several cities in the USSR and China. Many theories have been postulated to account for the emergence of this pandemic, including natural and unnatural origins. The purpose of this study was to use the modified Grunow–Finke risk assessment tool (modified Grunow‐Finke tool [mGFT]) to investigate the origin of the 1977 H1N1 pandemic. Data was collected from WHO archives and published documents. The assessment of the pandemic's origin involved the utilization of a modified version of the original Grunow–Finke risk assessment tool (GFT). Using the mGFT, the final score was 37 out of 60 points (probability: 62%), indicating a high likelihood that the Russian influenza pandemic of 1977 was of unnatural origin. Several variables supported this finding, including the sudden re‐emergence of a previously extinct strain, a genetic signature of laboratory modification for vaccine development, and unusual epidemiology. Inter‐rater reliability was moderate to high. By applying the mGFT to the 1977 Russian influenza pandemic, we established a high probability that this pandemic was of unnatural origin. Although this is not definitive, it is consistent with the possibility that it originated from an incompletely attenuated live influenza vaccine. The mGFT is a useful risk analysis tool to evaluate the origin of epidemics. [ABSTRACT FROM AUTHOR]

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The Advisory Committee on Immunization Practices (ACIP) recommends that health care personnel receive an annual influ- enza vaccine. In September 2023, ACIP recommended that everyone aged ≥6 months receive a 2023–2024 COVID-19 vaccine. Health care facilities, including acute care hospitals and nursing homes, report vaccination of health care personnel against influenza and COVID-19 to CDC’s National Healthcare Safety Network (NHSN). During October 2023–March 2024, NHSN defined up-to-date COVID-19 vaccination as receipt of a 2023–2024 COVID-19 vaccine. This analysis describes influenza and 2023–2024 COVID-19 vaccination coverage among health care personnel working in acute care hospitals and nursing homes during the 2023–24 respiratory virus season (October 1, 2023–March 31, 2024). Influenza vaccination coverage was 80.7% among health care personnel at acute care hospitals and 45.4% among health care personnel at nursing homes. Coverage of 2023–2024 COVID-19 vaccination was 15.3% among health care personnel at acute care hospitals and 10.5% among health care personnel at nursing homes. Respiratory viral diseases including influenza and COVID-19 pose risks to health care personnel in U.S. health care settings, and vaccination of health care personnel is an effective strategy for maintaining a healthy workforce and improving health care system resiliency. [ABSTRACT FROM AUTHOR]

Pregnancy is associated with increased risk for severe illness and complications associated with influenza infection. Insufficient knowledge about the risk for influenza among pregnant women and their health care providers in China is an important barrier to increasing influenza vaccination coverage and treating influenza and its complications among pregnant women. Improved influenza incidence estimates might promote wider vaccine acceptance and higher vaccination coverage. In Suzhou, active population-based surveillance during October 2018–September 2023 estimated that the annual rate of hospitalization for acute respiratory or febrile illness (ARFI) among women who were pregnant or <2 weeks postpartum was 11.1 per 1,000 live births; the annual rate of laboratoryconfirmed influenza-associated ARFI (influenza ARFI) hospitalization in this group was 2.1 per 1,000 live births. A majority of hospitalized pregnant or early postpartum patients with ARFI (82.6%; 2,588 of 3,133) or influenza ARFI (85.5%; 423 of 495) were admitted to obstetrics wards rather than respiratory medicine wards. Only one (0.03%) pregnant or postpartum ARFI patient had received influenza vaccination, and 31.3% of pregnant or postpartum women hospitalized for influenza ARFI received antiviral treatment; the lowest percentage of hospitalized women with influenza ARFI who received antiviral treatment was among women admitted to obstetrics and gynecology wards (29.6% and 23.1%, respectively), compared with 54.1% of those admitted to a respiratory medicine ward. These findings highlight the risk for influenza and its associated complications among pregnant and postpartum women, the low rates of influenza vaccination among pregnant women, and of antiviral treatment of women with ARFI admitted to obstetrics and gynecology wards. Increasing awareness of the prevalence of influenza ARFI among pregnant women, the use of empiric antiviral treatment for ARFI, and the infection control in obstetrics wards during influenza seasons might help reduce influenza-associated morbidity among pregnant and postpartum women. [ABSTRACT FROM AUTHOR]

Introduction: The SIR (Susceptible-Infected-Recovered) model is one of the simplest and most widely used frameworks for understanding epidemic outbreaks. Methods: A second-order dynamical system for the R variable is formulated using an infinite exponential series expansion, and a recursion relation is established between the series coefficients. A numerical approximation scheme for the R variable is also developed. Results: The proposed numerical method is compared to a double exponential (DE) nonlinear approximate analytic solution, which reveals two coupled timescales: a relaxation timescale, determined by the ratio of the model's time constants, and an excitation timescale, dictated by the population size. The DE solution is applied to estimate model parameters for a well-known epidemiological dataset—the boarding school flu outbreak. Discussion: From a theoretical standpoint, the primary contribution of this work is the derivation of an infinite exponential, Dirichlet, series for the model variables. Truncating the series yields a finite approximation, known as a Prony series, which can be interpreted as a sequence of coupled exponential relaxation processes, each with a distinct timescale. This apparent complexity can be approximated well by the DE solution, which appears to be of main practical interest. [ABSTRACT FROM AUTHOR]