Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.

The DNA damage response (DDR) network maintains genomic integrity, functions as a signaling hub that viruses exploit to drive pathogenesis, and constitutes a central interface between viral infection and host cell fate. This review discusses the molecular mechanisms by which viruses subvert host DDR pathways, with an emphasis on viral replication, latency, immune evasion, and host genomic instability. Representative examples include PARP1-dependent cccDNA stabilization by hepatitis B virus (HBV), MRN complex sequestration by herpes simplex virus type 1 (HSV-1) for immune evasion, ATM signaling modulation by human immunodeficiency virus (HIV) to maintain viral latency, and DDR activation triggered by RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and influenza A virus (IAV) via oxidative stress. We evaluate emerging DDR-targeted antiviral strategies, including restoring intrinsic host restriction, exploiting synthetic lethality of dysregulated DDR kinases, and therapeutically modulating DDR-innate immune crosstalk to restore antiviral surveillance (e.g., by stabilizing MRE11 or inhibiting PARP7). Bridging molecular insights with clinical translation, this review positions DDR targeting as a mechanism-driven, host-directed antiviral paradigm.

RNA viruses, major pathogens of humans and animals, are responsible for numerous inflammatory diseases. Commonly, mild RNA virus infection fails to trigger inflammatory diseases due to host immune homeostasis. However, severe RNA virus infection destroys immune homeostasis and causes hyperinflammation. The detail mechanism is still unclear. Here, we reported that SESN1 acts as a critical negative regulator of mitochondrial antiviral signaling protein (MAVS), a central hub protein in RNA-triggered innate immune response, by potentiating MAVS autophagic degradation to repress innate immune response. Upon low dose RNA virus infection, SESN1 level was decreased at infection early stage and was rebounded at late stage, which restrained SESN1-mediated MAVS degradation to clear virus at early stage and enhanced MAVS degradation to prevent excessive cytokines production at late stage. Whereas, SESN1 level was continuously impaired after high dose RNA virus infection, which caused robust cytokines production. Notably, we observed that the expression of SESN1 was markedly downregulated and negatively correlated with cytokine levels in patients with severe influenza. Replenishment of SESN1 effectively inhibited cytokines production in the Human Primary Bronchial/Tracheal Epithelial Cells infected with Influenza A virus PR8 and peripheral blood mononuclear cells of patients with severe influenza. Mechanistically, SESN1 interacted with MAVS and enhanced MAVS autophagic degradation via SQSTM1. Together, these findings revealed SESN1 was an important factor to regulate host innate immune response.

Introduction: The development of bivalent mucosal vaccines capable of providing protection against both influenza and SARS-CoV-2 is a major public health focus. While most COVID-19 vaccines target the spike (S) protein, the highly conserved nucleocapsid (N) protein represents a strategic target for cross-reactive, cell-mediated immunity. This study evaluates Corfluvec, an intranasal vaccine candidate based on an attenuated NS1-truncated influenza vector expressing a fragment of the SARS-CoV-2 N protein. Methods: Protective efficacy, including viral load and pathomorphological changes in the lungs and vessels, was evaluated in Syrian hamsters challenged with high and low doses of SARS-CoV-2 (lineage B.1.1). Cross-protective efficacy against homologous and heterologous influenza A strains (H1N1pdm09, H3N2, and A/PR/8/1934) was tested in a lethal murine model. Additionally, immunogenicity of Corfluvec applied via human-compatible delivery device was tested in cynomolgus macaques (Macaca fascicularis). Results: In Syrian hamsters, vaccination significantly reduced viral loads in the lungs and nasal turbinates. Histopathological analysis revealed a preservation of lung vascular integrity: vaccinated animals showed stable CD31 expression and controlled Ki-67 proliferative activity, accompanied by a marked reduction in vasculitis and perivascular edema compared to placebo controls. In mice, the vaccine provided 100% protection against homologous and heterologous influenza virus challenges. In macaques, the two-dose intranasal immunization was well-tolerated and induced significant systemic IgG and mucosal sIgA responses, alongside robust N-specific IFNγ+ T-cell activation. Conclusions: Corfluvec is a promising bivalent vaccine candidate that provides dual protection against influenza and COVID-19. Its ability to limit viral shedding from the upper respiratory tract and to mitigate SARS-CoV-2-induced pulmonary pathology, contributing to the preservation of lung vascular integrity, underscores the utility of mucosal immunization with Corfluvec as a valuable intranasal complement to current systemic vaccination strategies.

Background: Healthcare workers play a critical role in parental vaccine decision-making and the uptake of non-routine childhood vaccines. This study aimed to evaluate healthcare workers' knowledge, attitudes and behaviors regarding non-routine childhood vaccines, including rotavirus, meningococcal, human papillomavirus (HPV) and influenza vaccines. Methods: This cross-sectional study was conducted between October 2025 and March 2026 among healthcare workers in Türkiye. Data were collected using a structured questionnaire and the Attitudes Towards Vaccine Scale (ATVS), distributed through convenience and snowball sampling methods. Results: A total of 345 healthcare workers participated in the study. Recommendation behaviors differed significantly according to vaccine type (p < 0.001). Rotavirus and meningococcal vaccines were more frequently recommended than HPV and influenza vaccines. Although influenza vaccine had the highest awareness rate, it demonstrated the lowest recommendation rate and the lowest support for inclusion in the national immunization schedule. Physicians had significantly higher knowledge levels and vaccination attitude scores than non-physician healthcare workers (p < 0.001). ATVS scores were positively correlated with recommendation behaviors (ρ = 0.35, p < 0.001) and self-vaccination tendency (ρ = 0.34, p < 0.001). In multivariable analyses, higher vaccination attitude scores independently predicted greater self-vaccination tendency (OR = 1.07, 95% CI: 1.04-1.11, p < 0.001). Cost was the most commonly reported barrier to vaccine implementation. Conclusions: Positive attitudes toward non-routine childhood vaccines among healthcare workers do not necessarily translate into consistent recommendation behaviors across all vaccine types. Strategies targeting healthcare worker education, equitable vaccine access and standardized vaccine counseling practices may improve uptake and recommendation of optional childhood vaccines in Türkiye.

Influenza remains a significant national health security threat, particularly for vulnerable populations, as existing control measures do not fully mitigate its impact. This gap in protection is especially pronounced early in a pandemic when a well-matched vaccine may not yet be available, as well as in populations unable to mount an optimal vaccine response. Clinical studies support pre-exposure prophylaxis (PrEP) therapeutics as a promising complementary strategy to reduce influenza transmission and disease severity, potentially easing the strain on healthcare systems during outbreaks. This manuscript outlines the Biomedical Advanced Research and Development Authority's (BARDA's) target product profile (TPP) for a long-acting influenza PrEP product, reviews the current development landscape, and models the potential impact of early PrEP product deployment using agent-based modeling in a synthetic population of 19.5 million people across pandemic scenarios resembling the 1918, 1968, and 2009 influenza pandemics. Simulations showed that early deployment of a 70%-effective PrEP reduced cumulative and peak infections, delayed the epidemic peak, and provided the greatest benefit in less transmissible pandemics; at 40-50% coverage, PrEP fully mitigated a 2009-like pandemic and substantially reduced transmission in 1918- and 1968-like scenarios. The TPP defines key characteristics of an effective PrEP option for seasonal and pandemic influenza that (1) demonstrates a strong safety and tolerability profile across all populations; (2) targets a direct-acting antiviral mechanism of action; (3) reduces the relative risk of symptomatic influenza infection by at least 70% in an unvaccinated population and (4) provides single-dose, season-long protection to optimize patient adherence. In this context, integrating PrEP into influenza prevention strategies could improve control of virus spread, strengthen protection for high-risk groups, and significantly reduce the overall public health impact of seasonal and pandemic influenza.

Background: Acute sore throat (pharyngitis) accounts for 10-30% of ambulatory visits annually. Bacterial etiology, primarily Group A Streptococcus, is confirmed in only 20-34% of cases, and inappropriate antibiotic administration remains frequent, contributing to antimicrobial resistance. Community pharmacists play a key role in symptomatic management and stewardship, but real-world practices remain underexplored. Methods: A 16-item online questionnaire surveyed 629 Italian community pharmacists via professional networks, covering demographics, diagnostic tools, symptom assessment, treatment preferences, and follow-up. Responses were analyzed using descriptive statistics and interpreted within a multidisciplinary expert framework. Results: Italian community pharmacists (n = 629), predominantly mid-career and experienced individuals, prioritize targeted symptom questioning (flu-like signs (59.96%), fever (48.73%), pain intensity (49.64%)) and medical referral over formal diagnostic tools like the Centor criteria (unused in 53.66% of cases). A total of 46.74% report performing a Strep A test in fewer than 20% of patients. Topical sprays (83.33%) and lozenges (44.69%), especially containing flurbiprofen (94.19%), dominate recommendations, followed by systemic analgesics (45.79%). For mild cases, anti-inflammatory/analgesic sprays/lozenges (35.42%) and antiseptic lozenges (35.61%) dominate, while in severe cases, drugs with anti-inflammatory or analgesic effects are often preferred (72.47%). Most pharmacists request a follow-up (73.22%). Conclusions: Italian community pharmacists report a predominantly topical-first approach focused on symptomatic treatment and referral when appropriate. Diagnostic gaps and inconsistent follow-up represent actionable targets. The findings inform training outputs prioritizing simplified triage, expanded symptom checklists, spray/lozenge optimization, and 3-5-day call-backs. This work aims to promote pharmacists' antimicrobial stewardship to reduce antibiotic use while enhancing patient-centred sore throat care in Italy's pharmacy network.

Pandemic preparedness requires navigating trade-offs between health, economic, and social impacts; choices that often involve moral tensions. This study investigates how the Dutch public evaluates such trade-offs in the context of a potential outbreak of highly pathogenic avian influenza (HPAI). Using a discrete choice experiment (DCE) administered to a representative sample of 1,045 respondents from the LISS panel, we examined preferences across six policy outcomes: mortality, lasting physical and mental injuries, postponed healthcare, social restrictions, and one-off tax payments. A latent class logit model identified four distinct preference profiles, revealing substantial heterogeneity in moral and economic reasoning. Two classes exhibited taboo trade-off aversion (TTOA) when values such as life or human dignity were traded against monetary costs. Respondents displaying TTOA emphasized solidarity and governmental responsibility, while cost-sensitive groups prioritized economic efficiency. These findings highlight that public acceptance of pandemic policies depends not only on effectiveness and cost but also on perceived moral legitimacy. Accounting for TTOA in economic evaluation can improve the ethical considerations and societal acceptability of future pandemic preparedness strategies.

Influenza viruses are a constant threat to human health. Current vaccines often confer low to moderate protection against infection with seasonal viruses and little-to-no protection against pandemic viruses. Improved vaccines are needed. These vaccines will need to reliably elicit antibodies to conserved sites that are broadly protective. One strategy to do so is to design immunogens that present epitopes that are targeted by antibodies that are genetically similar, that humans have the genetic capacity to produce, and that are likely present in human naive B cell repertoires. Among the more recently described epitopes for broadly binding, protective antibodies are those on surfaces at protein-protein interfaces. This review will focus on describing many of these sites and the genetic features of antibodies that engage them. Interface epitopes are immunogenic, and antibodies to these sites are likely present in human repertoires following influenza infection or vaccination.

We present a case of Takotsubo cardiomyopathy (TCM), commonly known as broken heart syndrome, triggered by influenza A infection. Known cardiac complications of influenza include myocardial infarction, myocarditis, and pericarditis. Only a few cases of influenza have so far been reported that led to TCM. We discuss the presentation, investigations, and management of a 67-year-old woman who presented to the emergency department (ED) with chest pain and shortness of breath two weeks after being diagnosed with influenza A. We aim to highlight a rare cardiac complication of influenza infection so that clinicians can have a high index of suspicion for this association.

Background The COVID-19 pandemic coincided with substantial changes in respiratory virus circulation, healthcare utilization, and diagnostic testing. Although population-level influenza activity declined markedly in many settings during periods of stringent public health restrictions, patterns among children undergoing clinical testing remain less clearly understood. This study compared pediatric influenza test positivity across pre-pandemic, restriction-dominant pandemic, and post-restriction periods. Methods This retrospective cohort study included 18,035 children who underwent influenza A/B antigen testing at the Department of Pediatrics, Hisar Intercontinental Hospital, Istanbul, Türkiye, between January 2018 and May 2023. The study period was divided into the pre-pandemic (January 2018-February 2020), restriction-dominant pandemic (March 2020-June 2021), and post-restriction (July 2021-May 2023) periods. Influenza A and B antigens were detected in nasopharyngeal swab specimens using the GenBody Influenza A/B Ag rapid immunochromatographic assay. Tests performed for the same patient within 14 days were considered part of the same illness episode, and only the first eligible test was included. Influenza test positivity was compared across periods and according to age, sex, influenza type, and seasonality. Multivariable logistic regression was used to evaluate factors independently associated with influenza positivity. Results Of the 18,035 children, 6,691 were tested during the pre-pandemic period, 3,375 during the restriction-dominant period, and 7,969 during the post-restriction period. Influenza was detected in 1,699 (25.4%), 969 (28.7%), and 1,937 (24.3%) children, respectively (P<0.001). Although the proportion of positive tests was highest during the restriction-dominant period, both the testing volume and absolute number of detected cases were lower than before the pandemic. Influenza A positivity increased from 17.1% during the restriction-dominant period to 20.0% after restrictions were relaxed, whereas influenza B positivity declined from 11.6% to 4.4%. Seasonal positivity also varied substantially across the study periods. After adjustment for demographic characteristics, the epidemiological period remained independently associated with influenza test positivity. Conclusions Temporal changes in pediatric influenza test positivity coincided with changes in COVID-19 public health measures. The higher positivity among tested children during the restriction-dominant period occurred in the context of substantially reduced testing and should not be interpreted as increased population-level influenza circulation. Changes in healthcare utilization, testing behavior, and the composition of the tested population should be considered when interpreting these findings.