Isolation and genetic characteristics of Novel H4N1 Avian Influenza viruses in ChongQing, China.

BACKGROUND: Avian influenza viruses (AIVs) constitute significant zoonotic pathogens encompassing a broad spectrum of subtypes. Notably, the H4 subtype of AIVs has a pronounced ability to shift hosts. The escalating prevalence of the H4 subtype heightens the concern for its zoonotic potential, signaling an urgent need for vigilance. METHODS: During the period from December 2021 to November 2023, we collected AIV-related environmental samples and assessed them using a comprehensive protocol that included nucleic acid testing, gene sequencing, isolation culture, and resequencing. RESULTS: In this study, a total of 934 environmental samples were assessed, revealing a remarkably high detection rate (43.66%, 289/662) of AIV in the live poultry market. Notably, the H4N1 subtype AIV (cs2301) was isolated from the live poultry market and its complete genome sequence was successfully determined. Subsequent analysis revealed that cs2301, resulting from a reassortment event between wild and domesticated waterfowl, exhibits multiple mutations and demonstrates potential for host transfer. CONCLUSIONS: Our research once again demonstrates the significant role of wild and domesticated waterfowl in the reassortment process of avian influenza virus, enriching the research on the H4 subtype of AIV, and emphasizing the importance of proactive monitoring the environment related to avian influenza virus.

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.

Sangbaipi Decoction exerted in vitro and in vivo anti-Influenza Effect through inhibiting viral proteins.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Sangbaipi Decoction (SBPD) is an effective treatment for lung diseases caused by phlegm-heat obstruction according to Jingyue Quanshu, and soothes panting by purging the lung meridian. It is composed of anti-pyretic herbs (e.g., Scutellaria baicalensis Georgi and Coptis chinensis Franch.) and antitussive herbs (e.g., Cortex Mori and Armeniacae Semen Amarum). Therefore, we hypothesized that SBPD has therapeutic effects on lung injury caused by influenza virus. AIM OF THE STUDY: This study aimed to explore anti-influenza activity, active components, and mechanisms of SBPD. MATERIALS AND METHODS: The anti-influenza activities of SBPD were determined in 48 h drug-treated MDCK cell model using CPE and plaque reduction assays, and 24 h drug-treated A549 cells using qRT-PCR. The in vivo efficacy of SBPD (1.0g/kg/day and 0.5g/kg/day) was evaluated in PR8 infected BALB/c mice. The chemical component was assessed through HPLC-Q-TOF MS/MS analysis. Network pharmacology was built via TCMSP, GeneCards, DisgeNet, OMIM, DrugBank databases, and Cytoscape software. Additionally, TOA, HI and NAI assays were employed to investigate impact on the virus replication cycle with different concentrations of SBPD (2.5 mg/mL, 1.25 mg/mL, or 0.625 mg/mL). RESULTS: In MDCK infected with viruses A/PR/8/34, A/Hong Kong/1/68, or A/California/4/2009, the IC50 values of SBPD were 0.80 mg/mL, 1.20 mg/mL, and 1.25 mg/mL. In A549 cells, SBPD treatment reduced cytokine expression (e.g., TNF-α, IL-6, IL-1ß) (p < 0.05). In PR8 infected BALB/c mice, SBPD improved the survival rate of infected mice, reduced lung index (p < 0.05), protected lung tissue from pathological damage, and regulated cytokine overexpression (p < 0.05). 29 components of SBPD were identified in SBPD treated mouse serum including some phytochemicals targeting influenza proteins. HI and NAI assays suggested the potential antiviral mechanism of SBPD through inhibition of HA and NA. CONCLUSION: This study is the first to demonstrate the anti-influenza and the anti-inflammatory effects of SBPD in vitro and in vivo. Its major anti-influenza phytochemicals were explored and its inhibitory effects on HA and NA protein were proved. It provides more options for anti-influenza drug discovery.

Investigating the effects of Laggera pterodonta on H3N2-Induced inflammatory and immune responses through network pharmacology, molecular docking, and experimental validation in a mice model.

For centuries, Laggera pterodonta (LP), a Chinese herbal medicine, has been widely employed for treating respiratory infectious diseases; however, the mechanism underlying LP's effectiveness against the influenza A/Aichi/2/1968 virus (H3N2) remains elusive. This study aims to shed light on the mechanism by which LP combats influenza in H3N2-infected mice. First, we conducted quasi-targeted metabolomics analysis using liquid chromatography-mass spectrometry to identify LP components. Subsequently, network pharmacology, molecular docking, and simulation were conducted to screen candidate targets associated with AKT and NF-κB. In addition, we conducted a series of experiments including qPCR, hematoxylin-eosin staining, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay to provide evidence that LP treatment in H3N2-infected mice can reduce pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß, and MCP-1) while increasing T cells (CD3+, CD4+, and CD8+) and syndecan-1 and secretory IgA expression. This, in turn, aids in the prevention of excessive inflammation and the fortification of immunity, both of which are compromised by H3N2. Finally, we utilized a Western blot assay to confirm that LP indeed inhibits the AKT/NF-κB signaling cascade. Thus, the efficacy of LP serves as a cornerstone in establishing a theoretical foundation for influenza treatment.

The Uptake of Pneumococcal and Seasonal Influenza Vaccinations Based on Perceptions and Attitudes Toward the COVID-19 Vaccine Among Patients With Diabetes.

Objective In this study, we aimed to assess the rates of pneumococcal and seasonal influenza vaccinations among elderly and nonelderly diabetes patients and examine their perceptions and attitudes toward the coronavirus disease 2019 (COVID-19) vaccine. Methods A single-center study was conducted among patients with diabetes, employing a structured survey encompassing sociodemographic data, vaccination records, and the COVID-19 vaccine perception and attitude scale. Results Among the 280 diabetes patients in our study, the vaccination rates for COVID-19, seasonal influenza, and pneumococcal vaccines were 96.1%, 16.8%, and 17.5%, respectively. A higher cumulative dosage of the COVID-19 vaccine was associated with older age (r = 0.463; p<0.001), increased safety score (r = 0.479; p<0.001), and lower conspiracy theory score (r = -0.336; p<0.001). Participants who had received COVID-19 and influenza vaccines were observed to have significantly higher safety scores related to COVID-19 vaccines (p<0.001; d = 2.381 and p = 0.008; d = 0.525, respectively). Notably, vaccination rates for influenza and pneumococcus were significantly different between nonelderly and elderly patients (8.7% vs. 29.6%; p<0.001 and 13.4% vs. 24.1%; p = 0.022). Elderly patients with diabetes were 3.3 times more likely to receive the influenza vaccine than nonelderly participants [odds ratio (OR) = 3.319; 95% confidence interval (CI) = 1.592 - 6.920; p = 0.001] and had a higher safety score related to COVID-19 vaccines (OR = 1.076; 95% CI = 1.011 - 1.146; p = 0.021). Conclusions Both influenza and pneumococcal vaccination rates were below the desired targets in this study. The vaccination rates among the nonelderly diabetes population suggest that this group may be more likely to neglect to receive vaccination compared to the elderly diabetes population. The association between vaccination rates and post-pandemic safety perceptions highlights the critical need to implement public health strategies specifically designed to address and improve safety-related information dissemination.

Exploring the immune-inflammatory mechanism of Maxing Shigan Decoction in treating influenza virus A-induced pneumonia based on an integrated strategy of single-cell transcriptomics and systems biology.

BACKGROUND: Influenza is an acute respiratory infection caused by influenza virus. Maxing Shigan Decoction (MXSGD) is a commonly used traditional Chinese medicine prescription for the prevention and treatment of influenza. However, its mechanism remains unclear. METHOD: The mice model of influenza A virus pneumonia was established by nasal inoculation. After 3 days of intervention, the lung index was calculated, and the pathological changes of lung tissue were detected by HE staining. Firstly, transcriptomics technology was used to analyze the differential genes and important pathways in mouse lung tissue regulated by MXSGD. Then, real-time fluorescent quantitative PCR (RT-PCR) was used to verify the changes in mRNA expression in lung tissues. Finally, intestinal microbiome and intestinal metabolomics were performed to explore the effect of MXSGD on gut microbiota. RESULTS: The lung inflammatory cell infiltration in the MXSGD group was significantly reduced (p < 0.05). The results of bioinformatics analysis for transcriptomics results show that these genes are mainly involved in inflammatory factors and inflammation-related signal pathways mediated inflammation biological modules, etc. Intestinal microbiome showed that the intestinal flora Actinobacteriota level and Desulfobacterota level increased in MXSGD group, while Planctomycetota in MXSGD group decreased. Metabolites were mainly involved in primary bile acid biosynthesis, thiamine metabolism, etc. This suggests that MXSGD has a microbial-gut-lung axis regulation effect on mice with influenza A virus pneumonia. CONCLUSION: MXSGD may play an anti-inflammatory and immunoregulatory role by regulating intestinal microbiome and intestinal metabolic small molecules, and ultimately play a role in the treatment of influenza A virus pneumonia.

Comparative Analysis of Clinical Outcomes Using Propensity Score Matching: Coronavirus Disease 2019 vs. Seasonal Influenza in Korea.

BACKGROUND: The advent of the omicron variant and the formulation of diverse therapeutic strategies marked a new epoch in the realm of coronavirus disease 2019 (COVID-19). Studies have compared the clinical outcomes between COVID-19 and seasonal influenza, but such studies were conducted during the early stages of the pandemic when effective treatment strategies had not yet been developed, which limits the generalizability of the findings. Therefore, an updated evaluation of the comparative analysis of clinical outcomes between COVID-19 and seasonal influenza is requisite. METHODS: This study used data from the severe acute respiratory infection surveillance system of South Korea. We extracted data for influenza patients who were infected between 2018 and 2019 and COVID-19 patients who were infected in 2021 (pre-omicron period) and 2022 (omicron period). Comparisons of outcomes were conducted among the pre-omicron, omicron, and influenza cohorts utilizing propensity score matching. The adjusted covariates in the propensity score matching included age, sex, smoking, and comorbidities. RESULTS: The study incorporated 1,227 patients in the pre-omicron cohort, 1,948 patients in the omicron cohort, and 920 patients in the influenza cohort. Following propensity score matching, 491 patients were included in each respective group. Clinical presentations exhibited similarities between the pre-omicron and omicron cohorts; however, COVID-19 patients demonstrated a higher prevalence of dyspnea and pulmonary infiltrates compared to their influenza counterparts. Both COVID-19 groups exhibited higher in-hospital mortality and longer hospital length of stay than the influenza group. The omicron group showed no significant improvement in clinical outcomes compared to the pre-omicron group. CONCLUSION: The omicron group did not demonstrate better clinical outcomes than the pre-omicron group, and exhibited significant disease severity compared to the influenza group. Considering the likely persistence of COVID-19 infections, it is imperative to sustain comprehensive studies and ongoing policy support for the virus to enhance the prognosis for individuals affected by COVID-19.

Vaccination coverage during pregnancy and factors associated with refusal of recommended vaccinations: An Italian cross sectional study.

Background: The vaccines recommended during pregnancy are the Tdap, the influenza vaccine, and, during the SARS-CoV-2 pandemic, the vaccine against COVID-19. This survey aimed at determining vaccination coverage among pregnant women and adverse events, reasons for vaccine refusal, and factors associated with vaccine uptake. Methods: A single-center cross-sectional study was conducted on women who delivered between March and April 2022 at Careggi University Hospital in Florence, Italy. Information on the vaccinations (Tdap, influenza and COVID-19) received during pregnancy were collected through in-person interviews. Results: Among 307 enrolled women (response rate 99 % on a study population of 310 eligible women), 74 % of patients were vaccinated with Tdap, 82 % against COVID-19, and only 33 % against influenza. Vaccination coverage for Tdap and COVID-19 was significantly higher among Italian than foreign patients (80 % vs 51 %, p < 0.001 and 86 % vs 69 %, p = 0.002, respectively), and for Tdap was higher among patients followed in the private vs public care setting. The main reasons behind refusal of vaccinations were low risk perception of influenza (41 %), insufficient information received from the prenatal care provider regarding the Tdap (35 %), and, for the COVID-19, fear of vaccine side effects (64 %), and concerns about effects on the fetus (70 %). Conclusions: Adherence to the influenza vaccine was low because of reduced perception of the disease risks. The difference in vaccination coverage between Italians and foreigners is an example of healthcare disparity. Better information provided to patients about vaccines' efficacy and safety is advisable to increase acceptance of recommended vaccines.

Evaluating Pilot Implementation of 'PenCS Flu Topbar' App in Medical Practices to Improve National Immunisation Program-Funded Seasonal Influenza Vaccination in Central Queensland, Australia.

BACKGROUND: The 'PenCS Flu Topbar' app was deployed in Central Queensland (CQ), Australia, medical practices through a pilot programme in March 2021. METHODS: We evaluated the app's user experience and examined whether the introduction of 'PenCS Flu Topbar' in medical practices could improve the coverage of NIP-funded influenza vaccinations. We conducted a mixed-method study including a qualitative analysis of in-depth interviews with key end-users and a quantitative analysis of influenza vaccine administrative data. RESULTS: 'PenCS Flu Topbar' app users reported positive experiences identifying patients eligible for NIP-funded seasonal influenza vaccination. A total of 3606 NIP-funded influenza vaccinations was administered in the eight intervention practices, 14% higher than the eight control practices. NIP-funded vaccination coverage within practices was significantly higher in the intervention practices (31.2%) than in the control practices (27.3%) (absolute difference: 3.9%; 95% CI: 2.9%-5.0%; p < 0.001). The coverage was substantially higher in Aboriginal and Torres Strait Islander people aged more than 6 months, pregnant women and children aged 6 months to less than 5 years for the practices where the app was introduced when compared to control practices: incidence rate ratio (IRR) 2.4 (95% CI: 1.8-3.2), IRR 2.7 (95% CI: 1.8-4.2) and IRR 2.3 (1.8-2.9) times higher, respectively. CONCLUSIONS: Our evaluation indicated that the 'PenCS Flu Topbar' app is useful for identifying the patients eligible for NIP-funded influenza vaccination and is likely to increase NIP-funded influenza vaccine coverage in the eligible populations. Future impact evaluation including a greater number of practices and a wider geographical area is essential.

Evolution of H6N6 viruses in China between 2014 and 2019 involves multiple reassortment events.

H6N6 avian influenza viruses (AIVs) have been widely detected in wild birds, poultry, and even mammals. Recently, H6N6 viruses were reported to be involved in the generation of H5 and H7 subtype viruses. To investigate the emergence, evolutionary pattern, and potential for an epidemic of H6N6 viruses, the complete genomes of 198 H6N6 viruses were analyzed, including 168 H6N6 viruses deposited in the NCBI and GISAID databases from inception to January 2019 and 30 isolates collected from China between November 2014 and January 2019. Using phylogenetic analysis, the 198 strains of H6N6 viruses were identified as 98 genotypes. Molecular clock analysis indicated that the evolution of H6N6 viruses in China was constant and not interrupted by selective pressure. Notably, the laboratory isolates reassorted with six subtype viruses: H6N2, H5N6, H7N9, H5N2, H4N2, and H6N8, resulting in nine novel H6N6 reassortment events. These results suggested that H6N6 viruses can act as an intermediary in the evolution of H5N6, H6N6, and H7N9 viruses. Animal experiments demonstrated that the 10 representative H6N6 viruses showed low pathogenicity in chickens and were capable of infecting mice without prior adaptation. Our findings suggest that H6N6 viruses play an important role in the evolution of AIVs, and it is necessary to continuously monitor and evaluate the potential epidemic of the H6N6 subtype viruses.

Responding to the Return of Influenza in the United States by Applying Centers for Disease Control and Prevention Surveillance, Analysis, and Modeling to Inform Understanding of Seasonal Influenza.

We reviewed the tools that have been developed to characterize and communicate seasonal influenza activity in the United States. Here we focus on systematic surveillance and applied analytics, including seasonal burden and disease severity estimation, short-term forecasting, and longer-term modeling efforts. For each set of activities, we describe the challenges and opportunities that have arisen because of the COVID-19 pandemic. In conclusion, we highlight how collaboration and communication have been and will continue to be key components of reliable and actionable influenza monitoring, forecasting, and modeling activities.

Swine influenza A virus: challenges and novel vaccine strategies.

Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination strategies are often not updated frequently enough to address the continuously evolving nature of IAV-S, fail to induce broadly cross-reactive responses, are susceptible to interference, may enhance respiratory disease, and can be expensive to produce. Here, we review the challenges and current status of universal IAV-S vaccine research. We also detail the current standard of licensed vaccines and their limitations in the field. Finally, we review recently described novel vaccines and vaccine platforms that may improve upon current methods of IAV-S control.

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

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.

The phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity of Forsythiae Fructus: An updated systematic review.

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.

School closures due to seasonal influenza: a prospective data collection-based study of eleven influenza seasons-United States, 2011-2022.

Background: While numerous studies explore pandemic-associated school closures, literature is scant regarding seasonal influenza-associated closures. We previously reported summaries on COVID-19 pandemic-related school closures in the United States (US), which affected virtually all schools in the nation. The current prospective study aims to address the knowledge gap for seasonal influenza-related closures in the United States. Methods: We conducted systematic daily online searches from August 1, 2011 to June 30, 2022, to identify public announcements of unplanned school closures in the US lasting ≥1 day, selecting those that mentioned influenza and influenza-like illness (ILI) as reason for school closure (ILI-SCs). We studied ILI-SC temporal patterns and compared them with reported outpatient ILI-related healthcare visits. Findings: We documented that ILI-SCs occurred annually, with yearly totals ranging from 11 ILI-SCs in both the 2013-2014 and 2020-2021 school years to 2886 ILI-SCs in the 2019-2020 school year among more than 100,000 kindergarten through twelfth grade schools in the US. ILI-SCs occurred concurrently with widespread illness and the strongest correlations were observed during influenza A (H3N2)-dominant seasons, most notably in the 2016-2017 (Spearman rank correlation (rs) = 0.83) and the 2017-2018 (rs = 0.84) school years. ILI-SCs were heavily centered in U.S. Department of Health and Human Services Region 4 (states of Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee) [60% (6040/9166, Region 4/Total school closures)] and disproportionately impacted rural and lower-income communities. Interpretation: Outside of a pandemic, disease-related school closures are extreme and generally rare events for US schools and communities. Timely compilation of publicly available ILI-SC announcements could enhance influenza surveillance, particularly in severe influenza seasons or pandemics when ILI-SCs are prevalent. Funding: This work was supported by the U.S. Centers for Disease Control and Prevention. Co-authors (NZ, YZ, HG, AU) were or are US CDC employees, and FJ was a contractor through Cherokee Nation Operational Solutions, LLC, which supported FJ's salary, but had no additional role in the study.

Canadian vaccine safety surveillance reports following immunization with seasonal influenza vaccines, 2021-2022.

Background: Seasonal influenza vaccines (SIV) authorized for use in Canada have all undergone rigorous regulatory assessments for safety and effectiveness. Serious adverse events following immunization (AEFI) can occur, though they are rare. Continuous safety surveillance of vaccines during the post-marketing phase is a critical component of vaccination programs. This enables the detection of rare, late onset, or unexpected adverse events. An updated safety summary following the introduction of any new vaccines and/or formulations to immunization programs is necessary for refining the risk-benefit profile of a specific vaccine and maintaining public confidence. Here we provide an updated safety summary for SIVs distributed during the 2021/2022 influenza season from AEFI reports submitted to the Canadian Adverse Event Following Immunization Surveillance System (CAEFISS) and the Canadian Vigilance Database (CVD). Methods: We searched CAEFISS and CVD for individuals who were vaccinated with a SIV between October 1, 2021, and March 31, 2022. Descriptive statistics were calculated, including median age of vaccinated individuals, vaccines co-administered with SIV, and the most frequently reported AEFIs. Crude AEFI reporting rates were calculated by severity of the AEFI report, and SIV-type using doses distributed data. Medical reviews were conducted for reports including death, serious events (or outcomes) after SIV were administered alone, and selected adverse events (i.e., anaphylaxis, Guillain-Barré syndrome, febrile seizures, oculo-respiratory syndrome). Disproportionality analysis was used to identify potential safety signals among SIV and AEFI pairs. Results: There were 448 AEFI reports, with most AEFI classified as non-serious events (84.2%). The majority of reports described vaccination in adults at least 65 years of age (38.6%). The most frequently reported AEFIs were vaccination site pain, urticaria, pyrexia and rash. Medical review of AEFI reports did not find any evidence that reported deaths were related to vaccination with SIV. Among serious reports, nervous system disorders were the most commonly reported medical conditions. A higher number of events related to vaccination errors were also identified using disproportionality analysis. Conclusion: Findings from our analysis of reports to CAEFISS and CVD following vaccination with SIV are consistent with the known safety profile of SIVs distributed during the 2021/2022 influenza season. The majority of reports were non-serious with the most common AEFI symptoms occurring at the vaccination site or systemic symptoms that were self-limiting. The majority of vaccination error reports involved the administration of the vaccine at an inappropriate site, although no serious AEFIs were reported.

Antibody-independent surface plasmon resonance assays for influenza vaccine quality control.

Surface plasmon resonance (SPR)-based biosensors have emerged as a powerful platform for bioprocess monitoring due to their ability to detect biointeractions in real time, without the need for labeling. Paramount for the development of a robust detection platform is the immobilization of a ligand with high specificity and affinity for the in-solution species of interest. Following the 2009 H1N1 pandemic, much effort has been made toward the development of quality control platforms for influenza A vaccine productions, many of which have employed SPR for detection. Due to the rapid antigenic drift of influenza's principal surface protein, hemagglutinin, antibodies used for immunoassays need to be produced seasonally. The production of these antibodies represents a 6-8-week delay in immunoassay and, thus, vaccine availability. This review focuses on SPR-based assays that do not rely on anti-HA antibodies for the detection, characterization, and quantification of influenza A in bioproductions and biological samples. KEY POINTS: • The single radial immunodiffusion assay (SRID) has been the gold standard for the quantification of influenza vaccines since 1979. Due to antigenic drift of influenza's hemagglutinin protein, new antibody reagents for the SRID assay must be produced each year, requiring 6-8 weeks. The resulting delay in immunoassay availability is a major bottleneck in the influenza vaccine pipeline. This review highlights ligand options for the detection and quantification of influenza viruses using surface plasmon resonance biosensors.

Sivelestat (Neutrophil Elastase Inhibitor) as an Anti-inflammatory and Anti-viral Agent: An In Silico Study.

Background Sivelestat is a potent and specific neutrophil elastase inhibitor. It is clinically used in treating lung injury and respiratory distress syndrome. This engaged us to undertake the present study in which sivelestat was studied as an anti-inflammatory and anti-viral agent. Methodology The docking study of sivelestat on matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), chikungunya virus nonstructural protein-2 (CVnsP2) protease, and influenza A (H1N9) virus neuraminidase was assessed using the Chemistry at Harvard Macromolecular Mechanics (CHARMM) Dock (CDOCK) method. Furthermore, molecular physicochemical; bioactivity; absorption, distribution, metabolism, and excretion (ADME); toxicity; and Search Tool for Interacting Chemicals (STITCH) analyses were performed by using the Molinspiration (Molinspiration Cheminformatics, Slovensky Grob, Slovak Republic), SwissADME SwissADME (Swiss Institute of Bioinformatics, Quartier Sorge - Bâtiment Amphipôle, Switzerland), pkCSM (University of Melbourne, Melbourne, Australia), and STITCH-free online tools. Results The molecular physicochemical assessment of the ligand (sivelestat) showed no (zero) violation and agreed with the thumb rule of five, otherwise known as Lipinski's rule of five. ADME prediction of the ligand (sivelestat) is shown to possess a low gastrointestinal absorption (GIA) property. Similarly, toxicity analysis of the ligand (sivelestat) is predicted to have a hepatotoxicity effect. STITCH analysis reveals that the ligand (sivelestat) has exhibited interactions with the three human proteins. Conclusions The present molecular docking studies showed that the ligand (sivelestat) has successfully docked with all four enzymes of interest. Hence, the current finding has provided a good understanding of sivelestat as an effective suppressor activity against all four enzymes: MMP-2, MMP-9, CVnsP2 protease, and influenza neuraminidase.

Relative Effectiveness of the MF59®-Adjuvanted Influenza Vaccine Versus High-Dose and Non-Adjuvanted Influenza Vaccines in Preventing Cardiorespiratory Hospitalizations During the 2019-2020 US Influenza Season.

BACKGROUND: Adults ≥ 65 years of age have suboptimal influenza vaccination responses compared to younger adults due to age-related immunosenescence. Two vaccines were specifically developed to enhance protection: MF59-adjuvanted trivalent influenza vaccine (aIIV3) and high-dose egg-based trivalent influenza vaccine (HD-IIV3e). METHODS: In a retrospective cohort study conducted using US electronic medical records linked to claims data during the 2019-2020 influenza season, we compared the relative vaccine effectiveness (rVE) of aIIV3 with HD-IIV3e and a standard-dose non-adjuvanted egg-based quadrivalent inactivated influenza vaccine (IIV4e) for the prevention of cardiorespiratory hospitalizations, including influenza hospitalizations. We evaluated outcomes in the "any" diagnosis position and the "admitting" position on the claim. A doubly robust methodology using inverse probability of treatment weighting and logistic regression was used to adjust for covariate imbalance. rVE was calculated as 100 * (1 - ORadjusted). RESULTS: The study included 4,299,594 adults ≥ 65 years of age who received aIIV3, HD-IIV3e, or IIV4e. Overall, aIIV3 was associated with lower proportions of cardiorespiratory hospitalizations with diagnoses in any position compared to HD-IIV3e (rVE = 3.9% [95% CI, 2.7-5.0]) or IIV4e (9.0% [95% CI, 7.7-10.4]). Specifically, aIIV3 was more effective compared with HD-IIV3e and IIV4e in preventing influenza hospitalizations (HD-IIV3e: 9.7% [95% CI, 1.9-17.0]; IIV4e: 25.3% [95% CI, 17.7-32.2]). Consistent trends were observed for admitting diagnoses. CONCLUSION: Relative to both HD-IIV3e and IIV4e, aIIV3 provided improved protection from cardiorespiratory or influenza hospitalizations.