Assessing population-level target product profiles of universal human influenza A vaccines.

Influenza A has two hemagglutinin groups, with stronger cross-immunity to reinfection within than between groups. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-group protection, vaccines in current development stages may provide better protection against target groups than non-target groups. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal subtype dynamics. A broadly protective bivalent vaccine could lower the incidence of both groups and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target group when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-group protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.

Niños hospitalizados con influenza en un hospital pediátrico de Argentina durante 2019-2022: ¿qué ha cambiado luego de la pandemia por COVID-19? / Children with influenza admitted at a children's hospital in Argentina in the 2019­2022 period: What has changed after the COVID-19 pandemic?

Introducción. Durante 2020 y 2021, la circulación de los virus influenza se mantuvo por debajo de lo esperado en todo el mundo. En Argentina, en el año 2022 observamos una circulación ininterrumpida de influenza todo el año. Nuestros objetivos fueron describir los patrones de circulación y las características clínicas de niños internados con influenza. Población y métodos. Estudio retrospectivo, analítico, observacional. Se incluyeron todos los niños internados en un centro pediátrico con detección del virus influenza durante los años 2019-2022. Resultados. Se internaron 138 pacientes en 4 años; en 2019 se observó una tasa del 4,5/1000 egresos hospitalarios mientras que en 2022, fue del 15,1/1000. En 2020 y 2021 no hubo casos. En el 2019 la mayoría de los casos ocurrieron en invierno, la causa de la internación fue la infección respiratoria aguda baja (IRAB) en el 79 % y se detectó influenza A en el 92 % de los casos. En el 2022, la mayoría de los casos ocurrieron en primavera, el 62 % presentó IRAB y en el 56 % se detectó influenza A. Ambos períodos tuvieron similares frecuencias de vacunación y de comorbilidades. Conclusiones. En el 2022 se registraron más internaciones por influenza, lo que podría corresponder a que se realizaron métodos diagnósticos moleculares, que son más sensibles, y se observó un cambio en la estacionalidad con más casos en primavera. En 2019 predominó influenza A en infecciones del tracto respiratorio inferior, mientras que en el 2022 influenza A y B fueron similares, y hubo más formas extrapulmonares.

Introduction. During 2020 and 2021, the circulation of influenza virus remained below expectations worldwide. In Argentina, in 2022, we observed an uninterrupted circulation of influenza all year round. Our objectives were to describe the circulation patterns and clinical characteristics of hospitalized children with influenza. Population and methods. Retrospective, analytical, observational study. All children with influenza virus admitted to a children's hospital during the 2019­2022 period were included. Results. A total of 138 patients were admitted over 4 years; in 2019, the rate of hospital discharges was 4.5/1000, compared to 15.1/1000 in 2022. No cases were recorded in 2020 and 2021. In 2019, most cases were observed in the winter; in 79%, the cause was acute lower respiratory tract infection (ALRTI); influenza A was detected in 92%. In 2022, most cases occurred in the spring; 62% developed ALRTI; and influenza A was detected in 56%. Similar rates of vaccination and comorbidities were observed in both periods. Conclusions. In 2022, more hospitalizations due to influenza were recorded, which may have correlated with the use of more sensitive molecular diagnostic testing and a change in seasonality, with more cases observed in the spring. In 2019, influenza A predominated in lower respiratory tract infections, while in 2022, cases of influenza A and B were similar, with more extra-pulmonary forms.

Influenza vaccination and COVID-19 infection risk and disease severity: A systematic review and multilevel meta-analysis of prospective studies.

BACKGROUND: In light of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the influence of influenza vaccination on the risk and severity of Coronavirus Disease 19 (COVID-19) has been a subject of debate. This systematic review and meta-analysis of prospective studies aim to assess the association between influenza immunization and the risk of SARS-CoV-2 infection and subsequent COVID-19 disease severity. METHODS: A comprehensive search of PubMed and Embase databases was performed to identify prospective studies published before March 2024. We focused on evaluating the effect of influenza vaccination on SARS-CoV-2 infection risk and severe COVID-19 outcomes, such as hospitalization and mortality. The analysis employed a multilevel random effects meta-analysis approach. The risk of bias assessment was conducted using the Newcastle-Ottawa Scale. RESULTS: From an initial pool of 5,863 records, 14 studies were selected for inclusion. The aggregated data yielded a summary relative risk (SRR) that showed no significant protective correlation between influenza vaccination and SARS-CoV-2 infection risk (SRR 0.95, 95% confidence interval [CI] 0.81-1.11), COVID-19-associated hospitalization (SRR 0.90, 95% CI 0.68-1.19), or COVID-19-related mortality (SRR 0.83, 95% CI 0.56-1.23). CONCLUSIONS: This systematic review and meta-analysis, based exclusively on prospective studies, demonstrates the lack of a proven protective effect of influenza vaccination against COVID-19 and related outcomes. Our results do not support a significant protective effect of influenza vaccination against the risk or severe outcomes of COVID-19.

Mapping the interaction sites of human and avian influenza A viruses and complement factor H.

The complement system is an innate immune mechanism against microbial infections. It involves a cascade of effector molecules that is activated via classical, lectin and alternative pathways. Consequently, many pathogens bind to or incorporate in their structures host negative regulators of the complement pathways as an evasion mechanism. Factor H (FH) is a negative regulator of the complement alternative pathway that protects "self" cells of the host from non-specific complement attack. FH has been shown to bind viruses including human influenza A viruses (IAVs). In addition to its involvement in the regulation of complement activation, FH has also been shown to perform a range of functions on its own including its direct interaction with pathogens. Here, we show that human FH can bind directly to IAVs of both human and avian origin, and the interaction is mediated via the IAV surface glycoprotein haemagglutinin (HA). HA bound to common pathogen binding footprints on the FH structure, complement control protein modules, CCP 5-7 and CCP 15-20. The FH binding to H1 and H3 showed that the interaction overlapped with the receptor binding site of both HAs, but the footprint was more extensive for the H3 HA than the H1 HA. The HA - FH interaction impeded the initial entry of H1N1 and H3N2 IAV strains but its impact on viral multicycle replication in human lung cells was strain-specific. The H3N2 virus binding to cells was significantly inhibited by preincubation with FH, whereas there was no alteration in replicative rate and progeny virus release for human H1N1, or avian H9N2 and H5N3 IAV strains. We have mapped the interaction between FH and IAV, the in vivo significance of which for the virus or host is yet to be elucidated.

Utility of the Xpert Xpress CoV-2/Flu/RSV Plus Kit: A Glance at RSV Infection in Adults and Coinfection Rate.

Background: Viral infection is responsible for the majority of respiratory tract infections (RTI). This retrospective study evaluates the advantages of using the multiplex Xpert Xpress CoV-2/Flu/RSV plus kit in laboratory diagnosis of RTI caused by the most related viruses. Materials and Methods: Data were obtained from medical records between November 2021 and May 2023 for any sample tested using either the Xpert Xpress Flu/RSV kit, Xpert Xpress Flu kit, Xpert Xpress SARS-CoV-2 kit, and Xpert Xpress CoV-2/Flu/RSV plus kit. Results: Influenza virus A was detected in 8.5% (55/649) of the samples using the Flu PCR kit and in 4.9% (123/2538) using CoV-2/Flu/RSV plus kit, while influenza virus B detection rates were 3.7% (24/649) using the Flu PCR kit and 1.7% (43/2538) using the CoV-2/Flu/RSV plus kit. However, the detection rates using the two kits were comparable when evaluated for the same time period of the year. SARS-CoV-2 infections were detected in 16.9% (1545/9153) and 10.5% (266/2538) of the cases using the SARS-CoV-2 kit and CoV-2/Flu/RSV plus kits, respectively. Respiratory syncytial virus (RSV) was identified in 17.7% (66/372) of children using Flu/RSV kit; this number dropped significantly when age-targeted testing of RSV was performed due to involvements of adults. With the CoV-2/Flu/RSV plus kit, about 34% (35/103) of RSV infections detected were in patients aged >20 years; these cases would have previously been overlooked because adults are not routinely tested for RSV using the Flu/RSV kit. All coinfection cases (n = 16) were only detected with the CoV-2/Flu/RSV plus kit. Conclusion: The use of Xpert Xpress CoV-2/Flu/RSV plus kit not only results in shorter turnaround times through accurate detection of all four viruses, but also provides information on RSV infection in adults and coinfection rates.

Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

BACKGROUND: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. OBJECTIVE: We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. METHODS: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. RESULTS: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. CONCLUSIONS: The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

Influenza associated cardiac arrhythmia- a systematic review.

BACKGROUND: Influenza infection is rarely associated with cardiac conduction disorder. Cardiac arrhythmias due to such an infection have a full spectrum with ventricular arrythmias being the most common. METHODS: In our systematic review from PubMed, OVID Medline and EMBASE we have identified 23 articles describing arrythmias associated with different influenza infection. Most of them were case reports where ventricular arrhythmias were the most common. RESULTS: Complete heart block after influenza infection is usually temporary and a permanent pacemaker is rarely needed. There are reports of Influenza associated with arrhythmias in adults, neonates, and even fetuses in pregnant woman. Different mechanisms were described in literatures by which influenza causes arrhythmias such as interleukin 6 & tumor necrosis factor-alpha mediated inflammatory response, sympathetic overactivation, focal myocarditis and cleavage of angiotensin converting enzyme 2 protein which is cardioprotective. CONCLUSIONS: ACE 2 binder influenza viruses have more prone to be associated with cardiac conduction disorder. Oseltamivir for influenza infection is also associated with bradycardia and can shorten or lengthen QT segment. Influenza vaccination has found to be protective from cardiac arrhythmia.

Respiratory syncytial virus infection in adults: Differences with influenza.

INTRODUCTION: Respiratory syncytial virus (RSV) causes an acute respiratory illness similar to influenza, although there are few data comparing both of them in adults. The existence of clinical differences between these two infections could have implications for their management. MATERIALS AND METHODS: Retrospective observational cohort study including 63 adults with positive PCR for RSV and 221 for influenza during winter 2018-2019. Epidemiological, clinical characteristics and outcomes were contrasted between both groups. RESULTS: Compared to influenza, RSV-positive patients presented a higher association with active neoplasia (OR=2.9; 95% CI: 1.2-6.9), dependence for basic activities of daily living (OR=3.4; 95% CI: 1.4-8.2) and immunosuppression due to chronic glucocorticoid administration (OR=7.6; 95% CI: 1.6-36.1). At diagnosis, fever was less common (OR=0.3; 95% CI: 0.2-0.7), and C-reactive protein level ≥100mg/l was more frequent (OR=2.1; 95% CI: 1.0-4.5). They developed bacterial co-infection by Staphylococcus aureus in a higher proportion (OR=8.3; 95% CI: 1.5-46.9) and presented a greater need for admission to the intensive care unit (OR=5.4; 95% CI: 1.4-19.2). CONCLUSION: RSV is an important cause of respiratory illness in adults during the influenza season. It especially affects vulnerable patients with chronic underlying diseases, and has a higher morbidity than influenza. For all these reasons, specific detection, prevention and treatment of RSV is necessary in order to reduce the consumption of health care resources due to RSV disease in adults.

Children with influenza admitted at a children's hospital in Argentina in the 2019-2022 period: What has changed after the COVID-19 pandemic? / Niños hospitalizados con influenza en un hospital pediátrico de Argentina durante 2019-2022: ¿qué ha cambiado luego de la pandemia por COVID-19?

Introduction. During 2020 and 2021, the circulation of influenza virus remained below expectations worldwide. In Argentina, in 2022, we observed an uninterrupted circulation of influenza all year round. Our objectives were to describe the circulation patterns and clinical characteristics of hospitalized children with influenza. Population and methods. Retrospective, analytical, observational study. All children with influenza virus admitted to a children's hospital during the 2019-2022 period were included. Results. A total of 138 patients were admitted over 4 years; in 2019, the rate of hospital discharges was 4.5/1000, compared to 15.1/1000 in 2022. No cases were recorded in 2020 and 2021. In 2019, most cases were observed in the winter; in 79%, the cause was acute lower respiratory tract infection (ALRTI); influenza A was detected in 92%. In 2022, most cases occurred in the spring; 62% developed ALRTI; and influenza A was detected in 56%. Similar rates of vaccination and comorbidities were observed in both periods. Conclusions. In 2022, more hospitalizations due to influenza were recorded, which may have correlated with the use of more sensitive molecular diagnostic testing and a change in seasonality, with more cases observed in the spring. In 2019, influenza A predominated in lower respiratory tract infections, while in 2022, cases of influenza A and B were similar, with more extra-pulmonary forms.

Introducción. Durante 2020 y 2021, la circulación de los virus influenza se mantuvo por debajo de lo esperado en todo el mundo. En Argentina, en el año 2022 observamos una circulación ininterrumpida de influenza todo el año. Nuestros objetivos fueron describir los patrones de circulación y las características clínicas de niños internados con influenza. Población y métodos. Estudio retrospectivo, analítico, observacional. Se incluyeron todos los niños internados en un centro pediátrico con detección del virus influenza durante los años 2019-2022. Resultados. Se internaron 138 pacientes en 4 años; en 2019 se observó una tasa del 4,5/1000 egresos hospitalarios mientras que en 2022, fue del 15,1/1000. En 2020 y 2021 no hubo casos. En el 2019 la mayoría de los casos ocurrieron en invierno, la causa de la internación fue la infeccción respiratoria aguda baja (IRAB) en el 79 % y se detectó influenza A en el 92 % de los casos. En el 2022, la mayoría de los casos ocurrieron en primavera, el 62 % presentó IRAB y en el 56 % se detectó influenza A. Ambos períodos tuvieron similares frecuencias de vacunación y de comorbilidades. Conclusiones. En el 2022 se registraron más internaciones por influenza, lo que podría corresponder a que se realizaron métodos diagnósticos moleculares, que son más sensibles, y se observó un cambio en la estacionalidad con más casos en primavera. En 2019 predominó influenza A en infecciones del tracto respiratorio inferior, mientras que en el 2022 influenza A y B fueron similares, y hubo más formas extrapulmonares.

Does Vaccine Confidence Mediate the Relationship between Vaccine Literacy and Influenza Vaccination? Exploring Determinants of Vaccination among Staff Members of Nursing Homes in Tuscany, Italy, during the COVID-19 Pandemic.

BACKGROUND: Low coverage of influenza vaccination in nursing home (NH) staff may be attributed to factors such as vaccine confidence (VC) and vaccine literacy (VL). Our study aimed to evaluate the role of VL and VC in predicting the intention to get the influenza vaccine in a sample of employees of NHs in Tuscany, Italy. METHODS: Data from staff members in Tuscany were collected using an online questionnaire that examined influenza vaccination history, intentions, demographic information, health status, and VL. Statistical analyses explored the relationships between VC, VL, and vaccination intentions. RESULTS: The study included 1794 respondents, (86.3%) and assistants/aides (58.1%), with a median age of 46 years. The intention to get vaccinated was significantly higher among those with health risk conditions, and there was a positive association between VC and VL, specifically its interactive/critical component. The mediation analysis showed that VC completely mediated the relationship between VL and the intention to get vaccinated, with significant effects observed in different subgroups. CONCLUSIONS: VC is a key factor that mediates the effect of VL on vaccine intention. These results suggest that interventions aimed at improving VL alone may not be sufficient to increase vaccine uptake unless VC is also addressed.

Influenza as an important factor causing increased risk of patients' deaths, excessive morbidity and prolonged hospital stays.

Introduction: Influenza infection is associated with potential serious complications, increased hospitalization rates and a higher risk of death. Material and methods: A retrospective comparative analysis of selected indicators of hospitalization at the University Hospital in Wroclaw was conducted on patients with confirmed influenza infection and a control group during the 2018-2019 influenza season. The threshold for statistical significance of differences between the groups was set at p < 0.05. Results: The types of influenza viruses confirmed in the hospital patients were remarkably similar to those occurring in the general population in Poland. The largest numbers of influenza cases were observed at the departments related to internal medicine where patients with cardiac, lung and renal diseases were hospitalized. The risk of death among the patients with confirmed influenza infection was significantly higher than among the other patients. The highest risk of death was observed among the patients with confirmed influenza infection at the departments related to internal medicine. Considering patients from the entire hospital, the mean length of hospital stay for those with confirmed influenza was 2.13-fold longer than for those in the control group. Comparisons of the median, minimum and maximum lengths of hospitalization between the patients with confirmed influenza infection and the control group reveal even more distinct differences. Conclusions: Significant differences in the selected indicators of hospitalization were observed between the patients with confirmed influenza infection and the control group; they are associated with serious social costs, such as prolonged hospital stay and a higher risk of death during hospitalization in Poland.

Synthesis of multivalent sialyllactose-conjugated PAMAM dendrimers: Binding to SARS-CoV-2 spike protein and influenza hemagglutinin.

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and influenza viruses have spread around the world at an unprecedented rate. Despite multiple vaccines, new variants of SARS-CoV-2 and influenza have caused a remarkable level of pathogenesis. The development of effective antiviral drugs to treat SARS-CoV-2 and influenza remains a high priority. Inhibiting viral cell surface attachment represents an early and efficient means to block virus infection. Sialyl glycoconjugates, on the surface of human cell membranes, play an important role as host cell receptors for influenza A virus and 9-O-acetyl-sialylated glycoconjugates are receptors for MERS, HKU1 and bovine coronaviruses. We designed and synthesized multivalent 6'-sialyllactose-counjugated polyamidoamine dendrimers through click chemistry at room temperature concisely. These dendrimer derivatives have good solubility and stability in aqueous solutions. SPR, a real-time analysis quantitative method for of biomolecular interactions, was used to study the binding affinities of our dendrimer derivatives by utilizing only 200 micrograms of each dendrimer. Three SARS-CoV-2 S-protein receptor binding domain (wild type and two Omicron mutants) bound to multivalent 9-O-acetyl-6'-sialyllactose-counjugated and 6'-sialyllactose-counjugated dendrimers bound to a single H3N2 influenza A virus's HA protein (A/Hong Kong/1/1968), the SPR study results suggest their potential anti-viral activities.

A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

Rationale: Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness is more debated. Objectives: We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 ICU fatalities in a tertiary care center. Methods: In this monocentric, descriptive, retrospective case series, we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure who underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the Intensive Care Medicine influenza-associated pulmonary aspergillosis and the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) COVID-19-associated pulmonary aspergillosis consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. Measurements and Main Results: In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as a missed diagnosis upon autopsy in 8% of proven cases (n = 1/12), yet it was most frequently found as confirmation of a probable antemortem diagnosis (n = 11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed the highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza (n = 3) and COVID-19 (n = 3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. Conclusions: A proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case fatalities. Our findings highlight an important need for VAPA awareness, with an emphasis on mycological bronchoscopic work-up.

The FLURESP European commission project: cost-effectiveness assessment of ten public health measures against influenza in Italy: is there an interest in COVID-19 pandemic?

BACKGROUND: The FLURESP project is a public health research funded by the European Commission, with the objective to design a methodological framework to assess the cost-effectiveness of existing public health measures against human influenza pandemics. A dataset has been specifically collected in the frame of the Italian health system. As most of interventions against human influenza are relavant against other respiratory diseases pandemics, potential interests in COVID-19 are discussed. METHODS: Ten public health measures against human influenza pandemics pandemic were selected to be also relevant to other respiratory virus pandemics such as COVID 19: individual (hand washing, using masks), border control (quarantine, fever screening, border closure), community infection (school closure, class dismissal, social distancing, limitation of public transport), reduction of secondary infections (implementation of antibiotic therapy guidelines), pneumococcal vaccination for at-risk people, development of Intensive Care Unit (ICU) capacity, implementation of life support equipments in ICU, screening interventions, vaccination programs targeting health professional and targeting general population. RESULTS: Using mortality reduction as effectiveness criteria, the most cost-effective strategies are "reduction of secondary infections" and "implementation of life support equipment in ICU". The least cost-effective option whatever the level of pandemic events are screening interventions and mass vaccination. CONCLUSIONS: A number of intervention strategies against human influenza pandemics appears relevant against every respiratory virus, including the COVID-19 event. Measures against pandemics should be considered according to their expected effectiveness but also their costs for the society because they impose substantial burden to the population, confirming the interest of considering cost-effectiveness of public health measures to enlighten decision making.

Sliding dynamics and bifurcations of a human influenza system under logistic source and broken line control strategy.

This paper proposes a non-smooth human influenza model with logistic source to describe the impact on media coverage and quarantine of susceptible populations of the human influenza transmission process. First, we choose two thresholds $ I_{T} $ and $ S_{T} $ as a broken line control strategy: Once the number of infected people exceeds $ I_{T} $, the media influence comes into play, and when the number of susceptible individuals is greater than $ S_{T} $, the control by quarantine of susceptible individuals is open. Furthermore, by choosing different thresholds $ I_{T} $ and $ S_{T} $ and using Filippov theory, we study the dynamic behavior of the Filippov model with respect to all possible equilibria. It is shown that the Filippov system tends to the pseudo-equilibrium on sliding mode domain or one endemic equilibrium or bistability endemic equilibria under some conditions. The regular/virtulal equilibrium bifurcations are also given. Lastly, numerical simulation results show that choosing appropriate threshold values can prevent the outbreak of influenza, which implies media coverage and quarantine of susceptible individuals can effectively restrain the transmission of influenza. The non-smooth system with logistic source can provide some new insights for the prevention and control of human influenza.

Acceptance or rejection of vaccination against influenza and SARS-CoV2 viruses among primary care professionals in Central Catalonia. A cross-sectional study.

Background: With the outbreak of the SARS-CoV-2 pandemic, the uncertainty about the real impact of coinfection with other viruses, and the increased risk of mortality in the case of coinfection with the influenza virus, health authorities recommended an increase in influenza vaccination coverage among at-risk groups to minimize the possible impact on individuals and the healthcare system. Recommendations for influenza vaccination during the 2020-2021 campaign in Catalonia were focused on increasing vaccination coverage, especially for social and healthcare workers, elderly people and at-risk individuals of any age. The objectives for the 2020-2021 season in Catalonia were to reach 75 % for the elderly and for social and healthcare workers, and 60 % for pregnant women and at-risk groups. In the case of healthcare professionals and those over 65 years of age, the target was not met. Vaccination coverage reached 65.58 % and 66.44 %, respectively (in the 2019-2020 campaign it was 39.08 %).Analysing and following up on the background and context in which health professionals accept influenza vaccination will help develop strategies for long-term influenza vaccination campaigns. The present study looks at healthcare professionals in a specific territory where the reasons for acceptance or refusal of the influenza vaccine during the 2021-2022 vaccination campaign, as well as the reasons for acceptance or refusal of the COVID-19 vaccine, were analysed by means of an online survey. Methods: Calculations suggested that a random sample of 290 individuals would be sufficient to estimate, with 95% confidence and a precision of +/- 5 percentage units, a population percentage that was expected to be around 30%. The required replacement rate was 10%.The R statistical software (version 3.6.3) was used for the statistical analysis. Confidence intervals were 95 % and contrasts with a p-value of < 0.05 were considered significant. Findings: Of the 1921 professionals to whom the survey was sent, 586 (30.5%) responded to all the questions. 95.2% of respondents were vaccinated against COVID-19 and 66.2% against influenza.It was observed that the relationship between sociodemographic characteristics and the decision to get vaccinated was different for influenza and COVID-19. The reasons for accepting the COVID-19 vaccine with the highest percentage were firstly protecting family (82.2%), self-protection (74.9%) and also protecting patients (57.8%). Otherwise, other reasons not described in the survey (50%) and mistrust (42.3%) were the reasons for rejecting the COVID-19 vaccine.Regarding influenza, the most relevant reasons for which professionals got vaccinated were self-protection (70.7%), protecting family (69.7%) and protecting patients (58.4%). Reasons for refusing the influenza vaccine were reasons not mentioned in the survey (29.1%) and the low probability of suffering complications (27.4%). Interpretation: Analysing the context, territory, sector, and the reasons for both accepting and refusing a vaccine will help develop effective strategies. Although vaccination coverage against COVID-19 was very high throughout Spain, a marked increase in influenza vaccination in the context of COVID-19 was observed among healthcare professionals in the Central Catalonia region compared to the previous pre-pandemic campaign.

Decline in intravenous immunoglobulin titer against influenza virus A/H2N2 derived from donors in Japan.

Human influenza A/H2N2 can induce a pandemic in the future. This study evaluated the hemagglutination inhibition and neutralizing titers of intravenous immunoglobulin against A/H2N2 viruses, indicating the status of the donor population. In this study, the antibody titers decreased during the study period-2012-2021-suggesting a reduction in the immunity of the studied population.

Infección por virus respiratorio sincitial en adultos: diferencias con la gripe / Respiratory syncytial virus infection in adults: Differences with influenza

Introducción: El virus respiratorio sincitial (VRS) produce una enfermedad respiratoria aguda parecida a la gripe, aunque en adultos existen pocos datos que las comparen. La existencia de diferencias clínicas entre ambas infecciones podría conllevar implicaciones en su manejo. Materiales y métodos: Estudio observacional de cohortes retrospectivo incluyendo 63 adultos con PCR positiva para VRS y 221 para gripe durante el invierno 2018-2019. Se contrastaron las características epidemiológicas, clínicas y desenlaces entre ambos grupos. Resultados: En comparación con la gripe los pacientes VRS positivos asociaron mayor relación con neoplasia activa (OR=2,9; IC 95%: 1,2-6,9), dependencia para las actividades básicas de la vida diaria (OR=3,4; IC 95%: 1,4-8,2) e inmunosupresión por administración crónica de glucocorticoides (OR=7,6; IC 95%: 1,6-36,1). Al diagnóstico era menos común la presencia de fiebre (OR=0,3; IC 95%: 0,2-0,7) y más frecuente un nivel de proteína C reactiva≥100mg/l (OR=2,1; IC 95%: 1,0-4,5). Desarrollaron coinfección bacteriana por Staphylococcus aureus en mayor proporción (OR=8,3; IC 95%: 1,5-46,9) y presentaron una mayor necesidad de ingreso en la unidad de cuidados intensivos (OR=5,4; IC 95%: 1,4-19,2). Conclusión: El VRS es una causa importante de enfermedad respiratoria en adultos durante la época de gripe. Afecta especialmente a pacientes vulnerables con enfermedades crónicas de base, y presenta una morbilidad clínica superior a la gripe. Por todo ello es necesaria la detección, prevención y tratamiento específicos del VRS con el objetivo de reducir el consumo de recursos sanitarios que supone la enfermedad por VRS en adultos.(AU)

Introduction: Respiratory syncytial virus (RSV) causes an acute respiratory illness similar to influenza, although there are few data comparing both of them in adults. The existence of clinical differences between these two infections could have implications for their management. Materials and methods: Retrospective observational cohort study including 63 adults with positive PCR for RSV and 221 for influenza during winter 2018–2019. Epidemiological, clinical characteristics and outcomes were contrasted between both groups. Results: Compared to influenza, RSV-positive patients presented a higher association with active neoplasia (OR=2.9; 95% CI: 1.2–6.9), dependence for basic activities of daily living (OR=3.4; 95% CI: 1.4–8.2) and immunosuppression due to chronic glucocorticoid administration (OR=7.6; 95% CI: 1.6–36.1). At diagnosis, fever was less common (OR=.3; 95% CI: .2–.7), and C-reactive protein level ≥100mg/L was more frequent (OR=2.1; 95% CI: 1.0–4.5). They developed bacterial co-infection by Staphylococcus aureus in a higher proportion (OR=8.3; 95% CI: 1.5–46.9) and presented a greater need for admission to the intensive care unit (OR=5.4; 95% CI: 1.4–19.2). Conclusion: RSV is an important cause of respiratory illness in adults during the influenza season. It especially affects vulnerable patients with chronic underlying diseases, and has a higher clinical morbidity than influenza. For all these reasons, specific detection, prevention and treatment of RSV is necessary in order to reduce the consumption of health care resources due to RSV disease in adults.(AU)

Antiviral Responses of Tissue-resident CD49a+ Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease.

Rationale: Tissue-resident natural killer (trNK) cells have been identified in numerous organs, but little is known about their functional contribution to respiratory immunity, in particular during chronic lung diseases such as chronic obstructive pulmonary disease (COPD). Objectives: To investigate the phenotype and antiviral responses of trNK cells in murine cigarette smoke-induced experimental COPD and in human lung parenchyma from COPD donors. Methods: Mice were exposed to cigarette smoke for 12 weeks to induce COPD-like lung disease. Lung trNK cell phenotypes and function were analyzed by flow cytometry in both murine and human disease with and without challenge with influenza A virus. Measurements and Main Results: In the mouse lung, CD49a+CD49b+EOMES+ and CD49a+CD49b-EOMESlo NK cell populations had a distinct phenotype compared with CD49a- circulating NK cells. CD49a+ NK cells were more extensively altered earlier in disease onset than circulating NK cells, and increased proportions of CD49a+ NK cells correlated with worsening disease in both murine and human COPD. Furthermore, the presence of lung disease delayed both circulating and trNK cell functional responses to influenza infection. CD49a+ NK cells markedly increased their NKG2D, CD103, and CD69 expression in experimental COPD after influenza infection, and human CD49a+ NK cells were hyperactive to ex vivo influenza infection in COPD donors. Conclusions: Collectively, these results demonstrate that trNK cell function is altered in cigarette smoke-induced disease and suggests that smoke exposure may aberrantly prime trNK cell responsiveness to viral infection. This may contribute to excess inflammation during viral exacerbations of COPD.

A Malaysian consensus recommendation for the prevention of influenza in older persons.

BACKGROUND: Older persons are at high-risk of developing severe complications from influenza. This consensus statement was developed to provide guidance on appropriate influenza prevention strategies relevant to the Malaysian healthcare setting. METHODS: Under the initiative of the Malaysian Influenza Working Group (MIWG), a panel comprising 11 multi-speciality physicians was convened to develop a consensus statement. Using a modified Delphi process, the panellists reviewed published evidence on various influenza management interventions and synthesised 10 recommendations for the prevention of influenza among the aged population via group discussions and a blinded rating exercise. RESULTS: Overall, annual influenza vaccination is recommended for individuals aged ≥ 60 years, particularly those with specific medical conditions or residing in aged care facilities (ACFs). There is no preference for a particular vaccine type in this target population. Antiviral agents can be given for post-exposure chemoprophylaxis or when vaccine contraindication exists. Infection control measures should serve as adjuncts to prevent the spread of influenza, especially during Hajj. CONCLUSION: This consensus statement presents 10 evidence-based recommendations that can be adopted by healthcare providers to prevent influenza among the aged population in Malaysia. It could also serve as a basis for health policy planning in other lower- and middle-income countries.