Treatment Of Influenza Research Articles

Practice guideline of influenza vaccination and antiviral drugs use in children(2024 editon)

Influenza is the most common acute respiratory infectious diseases among children in China. The annual seasonal influenza outbreak has a significant impact on children's health, poses a significant disease and socioeconomic burden, and arouses a wide public concern. In recent years, a number of new influenza vaccines and influenza antivirals have been approved for use in children, expanding the choices for prevention and treatment of influenza. Pediatric Infection Group, Chinese Society of Infectious Diseases of Chinese Medical Association and Infection Group, Pediatric Expert Committee of National Health Commission Capacity Building and Continuing Education, and China Clinical Practice Guidelines Alliance Methodology Committee organized a multidisciplinary guideline development group (GDG) consisting of experts in pediatrics, infectious diseases,epidemiologists,health policy,and guideline methodology proposed eight key issues concerning influenza vaccination and antiviral use from a practice perspective. Through research question construction, evidence retrieval and synthesis, evidence appraisal and evidence-to-decision discussion, recommendations and implementation suggestions were formulated. This guideline is intended to provide guidance for pediatricians at different facility levels and healthcare providers engaged in vaccination services,and institutional professionals dealing with prevention and control of infectious diseases.

Revolutionizing Influenza Treatment: A Deep Dive into Targeted Drug Delivery Systems.

Influenza, a highly transmissible respiratory infection caused by influenza viruses A and B, poses a persistent threat to global public health due to its high mutation rate, ability to develop resistance to existing antiviral drugs, and capacity for rapid spread. Current treatment options, including four main classes of antiviral agents-adamantanes, neuraminidase inhibitors, RNA-dependent RNA polymerase inhibitors, and polymerase acidic endonuclease inhibitors- are limited by the emergence of drug-resistant viral strains, non-specific drug distribution, and adverse side effects. Moreover, the effectiveness of traditional vaccines is often compromised by antigenic drift and shift, necessitating the development of alternative therapeutic strategies. This review comprehensively explores the potential of novel targeted drug delivery systems to address these limitations and improve influenza management. Nanotechnology-based platforms, including lipid-based, polymer-based, inorganic, and hybrid nanoparticles, offer enhanced drug delivery through improved bioavailability, targeted action, and controlled release, thus minimizing systemic toxicity and optimizing therapeutic outcomes. Inhalation delivery systems such as dry powder inhalers (DPIs), nebulizers, and nanotechnology-based inhalation formulations provide direct delivery of antiviral agents to the respiratory tract, ensuring rapid onset of action with reduced systemic side effects. Transdermal delivery methods, including microneedle patches and hydrogel-based systems, offer non-invasive alternatives that enhance patient compliance and allow for sustained drug release. Furthermore, this review discusses recent innovations, such as responsive drug delivery systems and multifunctional nanoparticles capable of simultaneous delivery of multiple therapeutic agents, representing a significant advancement in the fight against influenza. These novel approaches promise improved targeting and efficacy and enable personalized treatment strategies, enhancing patient outcomes in both seasonal flu and pandemic scenarios. Integrating these advanced drug delivery systems into clinical practice could revolutionize the management of influenza, offering a promising pathway toward more effective and safer therapies.

Molecular mechanisms underlying the effects of hypo- and hyper-prolactinemia on spermatogenesis and fertility in male rats.

Hypo- and hyper-prolactinemia have deleterious effects on male reproduction, yet there is a dearth of information regarding the underlying mechanisms. The aim of this study was to delineate the molecular mechanisms by which hypo- and hyper-prolactinemia affects spermatogenesis and fertility in male rats. In vivo male rat models for hypo- and hyper-prolactinemia were established using dopamine receptor agonist, Bromocriptine (Brm), and antagonist, Fluphenazine (Flu), respectively. Effects on fertility and spermatogenesis were assessed by studying pre- and post-implantation loss, litter size, sperm parameters, hormonal profile, testicular histology, testicular cell population, and testicular transcriptome in rats. Treatment with Brm and Flu for 60 days led to subfertility, which was indicated by an increase in pre- and post-implantation loss and decrease in litter size, when mated with control female rats. Decreased sperm count was observed after both treatments, whereas reduced sperm motility was noted in Flu group. Serum FSH was unaffected, and LH was decreased by Flu treatment. Testosterone was decreased in both the groups, whereas estradiol was decreased in the Flu group. An arrest in spermatogenic cycle beyond round spermatids was observed in the Flu group. Additionally, testicular apoptosis in germ cells, mostly spermatocytes of Stage IX-XIV was noted in both the groups. Further, testicular RNA-Seq analysis revealed a total of 1539 and 824 differentially expressed genes/DEGs in Brm and Flu, respectively (Sequence Read Archive/SRA Database accession number: PRJNA1150513). Gene ontology and pathway analysis of DEGs highlighted enrichment of steroid metabolic pathway and ribosomal biogenesis pathway. Hub genes identified from the DEGs were validated by qPCR and the results showed that Uba52, Rps27a, Rpl23, Rps5, Rps16 were significantly down-regulated by Brm, whereas Rps27a, Rps29, Rps15, Rps27, Faul1 were significantly down-regulated by Flu. Hypo- and hyper-prolactinemia leads to subfertility and decreased sperm parameters possibly through an effect on steroid metabolism and ribosomal biogenesis pathway. Therefore, maintaining prolactin levels in physiological range is crucial.

A-236 Rapid multiplexed PCR (polymerase chain reaction) tests for respiratory disease improve process and time to diagnosis versus laboratory-based molecular testing

Abstract Background The Infectious Disease Society of America recommends molecular testing for symptomatic patients suspected of having COVID-19. Molecular tests can be performed at the point of care or in a centralized laboratory, using different methodologies, and can be singleplex or multiplex. Limited data are available examining the use of these tests in clinical practice and impact of different test types on patient outcomes; however, common antiviral treatments for both COVID-19 and influenza are more effective when taken earlier and are not indicated for use more than 5 and 2 days after symptom onset, respectively. The aim of this study was to describe the diagnostic journey for non-inpatients who received molecular testing for respiratory pathogens in the laboratory versus those who received testing using a rapid, multiplexed real-time RT-PCR test that can be performed at the point of care. Methods De-identified administrative claims were analyzed from July 1, 2020 through September 30, 2022 for commercially insured and Medicare Advantage enrollees in the Optum Labs Data Warehouse. Patients with ≥1 medical claim for a non-inpatient visit with a procedure code for testing for SARS-CoV-2 were identified; patients who received antigen testing at index were excluded. Patients were followed for up to 90 days. Two patient groups were selected for the final study sample: 1) Patients with ≥1 claim with CPT code 0240U or 0241U with a point-of-care or laboratory place of service on the index date (proprietary laboratory analyses codes for Xpert® Xpress CoV-2/Flu/RSV, or “Xpert Xpress”); and 2) Patients with other laboratory-based molecular testing on the index date. Standardized difference of >0.10 or <-0.10 was considered a significant imbalance in proportions or means. Results In total, 51,602 patients received testing with Xpert Xpress while 317,192 received laboratory testing. Patients who were tested with Xpert Xpress were significantly older (mean 49.82 vs 42.19, SD 0.3), had a higher Charlson Comorbidity Index (mean 0.7 vs 0.35, SD 0.29), and were more likely to have a respiratory risk factor (6.09% vs 2.38%, SD 0.19). On average, patients who were tested with Xpert Xpress had significantly fewer tests for SARS-CoV-2 on the index date (mean 1.2 vs 1.58, SD -0.55), and fewer tests for SARS-CoV-2, influenza, or RSV on the index date and through the end of the 90-day fixed follow-up period (mean 1.64 vs 2.57, SD -0.45). They were also significantly more likely to be diagnosed with COVID-19 on the index date (23.31% vs 16.53%, SD 0.17). Among patients with a diagnosis for COVID-19, mean time to diagnosis was significantly shorter among patients tested with Xpert Xpress (4.85 vs 8.86 days, SD -0.27; median 0 vs 4 days). This finding was also consistent for influenza (4.05 vs 20.28 days, SD -0.74; median 0 vs 5 days). Conclusions Testing with Xpert Xpress at index resulted in fewer total tests and faster diagnosis compared to testing in the laboratory. Rapid, multiplex PCR testing provides a faster time to diagnosis and may support more appropriate and effective treatment.

The efficacy of azithromycin in the treatment of influenza A infection: A systematic review

Background The WHO recommendation against the use of macrolides reflects the little low-quality evidence about the effect of azithromycin (AZ) on influenza A infection. Considering recent reports about AZ use despite the WHO’s unfavorable recommendations, we aimed to test the evidence for the usage of AZ in the treatment of influenza A infection. Methods Various online databases were searched till August 2023 and thorough text and evidence evaluation resulted in selecting 7 studies. Results The selected reports included randomized control trials (two), cohort (three), case/control (one) studies, and one case report. Pooling of the results was unattainable due to the variability among studies in patient criteria, study outcomes, and study designs. Based on the limited reports with insufficient evidence, a recommendation for the use of AZ in the treatment regimen was not possible despite the associated reduction in inflammatory cytokines by AZ administration and the absence of significant adverse effects or mortality in hospital-admitted or ICU patients. While these findings support the current guidelines for the treatment of influenza A infection, the evidence behind these guidelines and treatment characteristics were illustrated. Conclusion AZ shows a potential symptom improvement and pro-inflammatory laboratory indices in influenza A patients. Another positive aspect is the absence of complications associated with AZ administration to critically ill patients and acceptable prognosis. However, it is crucial to have more quality research on this matter that focuses on the indication of the use of AZ, and the timing of initiation, dosage, and duration of treatment while monitoring adverse events.

Efficacy and safety of ZX-7101A, an inhibitor of influenza cap-dependent endonuclease, in adults with uncomplicated influenza: a randomised, double-blind, placebo-controlled phase 2/3 Trial

ObjectivesTo evaluate the efficacy and safety of ZX-7101A: an inhibitor of influenza viral cap-dependent endonuclease, in adults with uncomplicated influenza and explore treatment-emergent resistance. MethodsWe conducted a randomized, double-blind, placebo-controlled, adaptive-design phase 2 and phase 3 studies (ZX-7101A-202) in adults with uncomplicated influenza. Eligible patients were randomised 1:1:1 to receive a single dose of 40 or 80mg ZX-7101A or placebo, stratified by body weight and baseline composite symptom score. The primary efficacy endpoint was time to alleviation of influenza symptoms (TTAS) in intention-to-treat infected (ITTI) population. ResultsThe phase 2 trial suggested a significantly shorter in TTAS for ZX-7101A compared to placebo: the median TTAS of 40 or 80mg ZX-7101A was 34.7 hours (95% confidence interval [CI], 22.8-43.4; p=0.005) and 45.8 hours (95%CI, 32.0-66.3; p=0.020), compared with 63.6 hours (95%CI, 43.9-93.4) in the placebo group.In the phase 3 trial, the TTAS of both ZX-7101A dose groups was significantly shortened relative to the placebo: the median TTAS was shortened to 48.4 hours (95%CI, 40.5-55.6) for 40mg and 39.4 hours (95%CI, 35.8-49.3) for 80mg, compared with 62.9 hours (95%CI, 56.4-69.3) for placebo (p=0.003 and p<0.001, respectively). In the safety population, ZX-7101A treatment was associated with fewer adverse events (AEs), with 41.8% (100/239) in the 40mg group, 44.2% (106/240) in the 80mg group, and 53.8% (129/240) in the placebo group. The majority of AEs were mild or moderate. Emergence of resistance to ZX-7101A through I38T amino acid substitution was detected in 5/122 (4.1%) patients. ConclusionsZX-7101A was an effective treatment for influenza with a single dose of either 40mg or 80mg, with more rapid alleviation of influenza symptoms versus placebo. No safety concerns were identified with single-dose treatment of ZX-7101A.

Inhibition of influenza virus infection in mice by pulmonary administration of a spray dried antiviral drug

Increasing resistance to antiviral drugs approved for the treatment of influenza urges the development of novel compounds. Ideally, this should be complemented by a careful consideration of the administration route. 6′siallyllactosamine-functionalized β-cyclodextrin (CD-6′SLN) is a novel entry inhibitor that acts as a mimic of the primary attachment receptor of influenza, sialic acid. In this study, we aimed to develop a dry powder formulation of CD-6′SLN to assess its in vivo antiviral activity after administration via the pulmonary route. By means of spray drying the compound together with trileucine, a dispersion enhancer, we created a powder that retained the antiviral effect of the drug, remained stable under elevated temperature conditions and performed well in a dry powder inhaler. To test the efficacy of the dry powder drug against influenza infection in vivo, infected mice were treated with CD-6′SLN using an aerosol generator that allowed for the controlled administration of powder formulations to the lungs of mice. CD-6′SLN was effective in mitigating the course of the disease compared to the control groups, reflected by lower disease activity scores and by the prevention of virus-induced IL-6 production. Our data show that CD-6′SLN can be formulated as a stable dry powder that is suitable for use in a dry powder inhaler and is effective when administered via the pulmonary route to influenza-infected mice.

A real-world disproportionality analysis of baloxavir marboxil: post-marketing pharmacovigilance data

ABSTRACT Objective Baloxavir marboxil (hereafter referred to as baloxavir) is the only cap-dependent endonuclease inhiabitor approved for the treatment and prevention of influenza. However, as a new drug marketed in 2018, the long-term safety of baloxavir in large sample population was unclear. This study aims to evaluate baloxavir-associated adverse events (AEs) through data mining of the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS). Methods Disproportionality analysis was conducted to assess the association between baloxavir and its AEs. Data were collected from FAERS from March 2018 to June 2023. After standardizing the data, signal quantification techniques including ROR, PRR, BCPNN and MGPS were used for analysis. Results A total of 49 significant baloxavir-related preferred terms (PTs) in 20 system organ classes (SOCs) were identified in our data analysis. Compared to baloxavir’s FDA label, some new PTs emerged, with the top 10 being pneumonia, loss of consciousness, rhabdomyolysis, seizure, altered state of consciousness, hepatic function abnormal, delirium, depressed level of consciousness, encephalopathy and cardio-respiratory arrest. Conclusion In clinical application of baloxavir, attention should be paid to the new AE signals in addition to the those recorded in the labels, so as to ensure the safety of the patients.

PEG-SeNPs as therapeutic agents inhibiting apoptosis and inflammation of cells infected with H1N1 influenza A virus

The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Development and characterization of a cyclodextrin-based delivery system for enhanced pharmacokinetic and safety profile of oseltamivir

AbstractOseltamivir (OST) phosphate is a prodrug, metabolized by hepatic carboxylesterase to its active metabolite (oseltamivir carboxylate). OST is efficient in treatment of influenza, in both children and adults. The protein bonding of the prodrug and its active metabolite is low (42% and 3%, respectively). It has a short half-life 1–3 h but its active metabolite has a half-life of 6–10 h, permitting twice daily administration. The most common side effect is gastrointestinal disturbances that are usually nausea and vomiting and can be reduced when taken simultaneously with food. OST phosphate is a white powder with bitter taste and the marketed oral suspension uses sorbitol for masking it. Cross-linked cyclodextrin polymers are known for their ability to increase the dissolution rate, solubility, stability, and permeability of insoluble drugs and provide prolonged release. Therefore, they are promising drug delivery systems that could improve its pharmacokinetic properties and patient adherence. In this study we focused on developing a therapeutic system of OST using cyclodextrin polymer crosslinked with pyromellitic dianhydride (PMDA CD) to enhance its pharmacokinetic properties and to improve its compliance. PMDA CD polymer and PMDA CD polymer complex with OST were prepared. Physicochemical characterization by FTIR spectra, thermal analysis, DLS, SEM and EDX confirmed the existence of interaction between the two components. The prepared complex has a different pharmaceutical profile compared to OST, with higher stability and a controlled dissolution profile. Toxicity studies showed that the polymer complex has lower toxicity than OST, suggesting the protective effect of the polymer.

The Molecular Mechanism of Shufeng Jiedu Capsules in the Treatment of Influenza: A Comprehensive Analysis Based on Network Pharmacology, Bioinformatics, and Molecular Docking

The Molecular Mechanism of Shufeng Jiedu Capsules in the Treatment of Influenza: A Comprehensive Analysis Based on Network Pharmacology, Bioinformatics, and Molecular Docking

Recommendations for Prevention and Control of Influenza in Children, 2024-2025: Technical Report.

This technical report accompanies the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2024 to 2025 season. The rationale for the American Academy of Pediatrics recommendation for annual influenza vaccination of all children without medical contraindications starting at 6 months of age is provided. Influenza vaccination is an important strategy for protecting children and the broader community against influenza. This technical report summarizes recent influenza seasons, morbidity and mortality in children, vaccine effectiveness, and vaccination coverage and provides detailed guidance on vaccine storage, administration, and implementation. The report also provides a brief background on inactivated (nonlive) and live attenuated influenza vaccines, available vaccines for the 2024-2025 influenza season, vaccination during pregnancy and breastfeeding, diagnostic testing for influenza, and antiviral medications for treatment and chemoprophylaxis. Strategies to promote vaccine uptake are emphasized.

Recommendations for Prevention and Control of Influenza in Children, 2024-2025: Policy Statement.

This statement updates the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccines and antiviral medications in the prevention and treatment of influenza in children during the 2024-2025 influenza season. A detailed review of the evidence supporting these recommendations is published in the accompanying technical report (www.pediatrics.org/cgi/doi/10.1542/peds.2024-068508). The American Academy of Pediatrics recommends annual influenza vaccination of all children without medical contraindications starting at 6 months of age. Children are at risk for hospitalization and death from influenza. Influenza vaccination is an important strategy for protecting children and the broader community as well as reducing the overall burden of respiratory illnesses when other viruses are cocirculating. Any licensed influenza vaccine appropriate for age and health status can be administered, ideally as soon as possible in the season, without preference for one product or formulation over another. All licensed influenza vaccines for use in the United States are trivalent for the 2024-2025 influenza season. Antiviral treatment of influenza is recommended for children with suspected (eg, influenza-like illness [fever with either cough or sore throat]) or confirmed influenza who are hospitalized or have severe or progressive disease or have underlying conditions that increase their risk of complications of influenza, regardless of duration of illness. Antiviral treatment should be initiated as soon as possible. Antiviral treatment may be considered in the outpatient setting for symptomatic children who are not at high risk for influenza complications with suspected or confirmed influenza disease, if treatment can be initiated within 48 hours of illness onset. Antiviral treatment may also be considered for children with suspected or confirmed influenza disease whose siblings or household contacts either are younger than 6 months or have a high-risk condition that predisposes them to complications of influenza. Antiviral chemoprophylaxis is recommended for the prevention of influenza virus infection as an adjunct to vaccination in certain individuals, especially exposed children who are asymptomatic and are at high risk for influenza complications but have not yet been immunized or those who are not expected to mount an effective immune response.

ProcCluster® and procaine hydrochloride inhibit the replication of influenza A virus in vitro.

Treatment of influenza A virus infections is currently limited to few direct acting antiviral substances. Repurposing other established pharmaceuticals as antivirals could aid in improving treatment options. This study investigates the antiviral properties of ProcCluster® and procaine hydrochloride, two derivatives of the local anesthetic procaine, in influenza A virus infection of A549, Calu-3 and MDCK cells. Both substances inhibit replication in all three of these cell lines in multi-cycle experiments. However, cell line-dependent differences in the effects of the substances on viral RNA replication and subsequent protein synthesis, as well as release of progeny viruses in single-cycle experiments can be observed. Both ProcCluster® and procaine hydrochloride delay endosome fusion of the virus early in the replication cycle, possibly due to the alkaline nature of the active component procaine. In A549 and Calu-3 cells an additional effect of the substances can be observed at late stages in the first replication cycle. Interestingly, this effect is absent in MDCK cells. We demonstrate that ProcCluster® and procaine hydrochloride inhibit phospholipase A2 (PLA2) enzymes from A549 but not MDCK cells and confirm that specific inhibition of calcium independent PLA2 but not cytosolic PLA2 has antiviral effects. We show that ProcCluster® and procaine hydrochloride inhibit influenza A virus infection at several stages of the replication cycle and have potential as antiviral substances.

Citrus-derived flavanones as neuraminidase inhibitors: In vitro and in silico study

Neuraminidase (NA) has been well-studied as a therapeutic target for Influenza. However, resistance to the influenza virus has been observed recently. Out of special interest in the utilization of dietary antivirals from citrus, in vitro inhibition activity against NA and in silico studies including molecular docking, molecular dynamic simulation, and a predictive ADMET study, were performed on five citrus-derived flavanones. Encouragingly, citrus-derived flavanones displayed comparable or even more potent in vitro inhibitory activity than oseltamivir carboxylate against NA. Orange peel extract exhibited higher activity than hesperidin. Among the tested compounds, neohesperidin, forming strong hydrogen-bonding interactions with key arginine residues, exhibited the most effective inhibitory activity against NAs from C. perfringens, consistent with the results of molecular dynamics simulations. Although the molecular docking results were inconsistent with the in vitro activity, the binding energy was identical against the wild-type and mutant, suggesting a lower likelihood of developing drug resistance. Moreover, predictive ADMET studies showed favorable pharmacokinetic properties for the tested compounds. Overall, citrus fruit peel emerges as a promising dietary supplement for prevention and treatment of influenza. These findings elucidate the impact of flavanones on NA activity, and the analysis of their binding modes provides valuable insights into the mechanism of NA inhibition.

The Development History, Structural Composition, and Functions of Influenza Viruses and the Progress of Influenza Virus Inhibitors in Clinics and Clinical Trials.

Flu is an acute respiratory disease caused by influenza viruses. The influenza viruses are classified as Alphainfluenzavirus (influenza A virus, IAV), Betainfluenzavirus (influenza B virus, IBV), Gammainfluenzavirus (influenza C virus, ICV), and Deltainfluenzavirus (influenza D virus, IDV) according to the antigenicity of nucleoproteins (NPs) and matrix (M) proteins in vivo. It is estimated that the seasonal influenza epidemics will cause about 3-5 million cases of serious illness and 290,000-650,000 deaths in the world every year, while influenza A virus is the leading cause of infection and death. Neuraminidase (NA) is one of the most critical targets for the development of anti-influenza virus drugs, and the main drugs clinically applied for the treatment of flu are neuraminidase inhibitors. However, various mutant strains have developed resistance to these inhibitors (For example, the substrains of H274Y in H1N1, H5N1, and E119V in H3N2 have developed resistance to Oseltamivir). Influenza viruses mutate frequently, and new substrains emerge constantly, and the pandemics caused by the new substrains will break out at any time. Therefore, it is urgent to develop new and wide-spectrum influenza virus inhibitors for overcoming the emerging influenza pandemic. Here, we focus on describing the progress of influenza virus inhibitors in clinics and clinical trials to provide a comprehensive reference for the researchers.

An integrative pharmacology-based study on the efficacy and mechanism of essential oil of Chaihu Guizhi Decoction on influenza A virus induced pneumonia in mice

Ethnopharmacological relevanceChaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. Aim of the studyTo evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. Materials and methodsCGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. Results(E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 μg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. ConclusionsThe findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.

Antivirals for treatment of severe influenza: a systematic review and network meta-analysis of randomised controlled trials

The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza. We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023, that enrolled hospitalised patients with suspected or laboratory-confirmed influenza and compared direct-acting influenza antivirals against placebo, standard care, or another antiviral. Pairs of coauthors independently extracted data on study characteristics, patient characteristics, antiviral characteristics, and outcomes, with discrepancies resolved by discussion or by a third coauthor. Key outcomes of interest were time to alleviation of symptoms, duration of hospitalisation, admission to intensive care unit, progression to invasive mechanical ventilation, duration of mechanical ventilation, mortality, hospital discharge destination, emergence of antiviral resistance, adverse events, adverse events related to treatments, and serious adverse events. We conducted frequentist network meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. This study is registered with PROSPERO, CRD42023456650. Of 11 878 records identified by our search, eight trials with 1424 participants (mean age 36-60 years for trials that reported mean or median age; 43-78% male patients) were included in this systematic review, of which six were included in the network meta-analysis. The effects of oseltamivir, peramivir, or zanamivir on mortality compared with placebo or standard care without placebo for seasonal and zoonotic influenza were of very low certainty. Compared with placebo or standard care, we found low certainty evidence that duration of hospitalisation for seasonal influenza was reduced with oseltamivir (mean difference -1·63 days, 95% CI -2·81 to -0·45) and peramivir (-1·73 days, -3·33 to -0·13). Compared with standard care, there was little or no difference in time to alleviation of symptoms with oseltamivir (0·34 days, -0·86 to 1·54; low certainty evidence) or peramivir (-0·05 days, -0·69 to 0·59; low certainty evidence). There were no differences in adverse events or serious adverse events with oseltamivir, peramivir, and zanamivir (very low certainty evidence). Uncertainty remains about the effects of antivirals on other outcomes for patients with severe influenza. Due to the small number of eligible trials, we could not test for publication bias. In hospitalised patients with severe influenza, oseltamivir and peramivir might reduce duration of hospitalisation compared with standard care or placebo, although the certainty of evidence is low. The effects of all antivirals on mortality and other important patient outcomes are very uncertain due to scarce data from randomised controlled trials. World Health Organization.

Research Progress of Chinese Medicine in the Treatment of Influenza A in Children

Research Progress of Chinese Medicine in the Treatment of Influenza A in Children

An Age-Specific Crisis Awareness Survey of COVID-19 Vaccines and Treatments Among Healthy Japanese Adults.

Introduction and objectives The spread of coronavirus disease 2019 (COVID-19) has been a worldwide phenomenon. This study conducted a chronological survey of crisis awareness regarding COVID-19 within different age groups. Methods An internet-based survey was performed on healthy Japanese adults to investigate the value of a hypothetical prophylactic vaccine and therapeutic drug for COVID-19 in each age group. In total, 12 groups comprising males and females in six different age groups, leading to a total of 1,200 individuals, were surveyed on a weekly basis. The survey was conducted on Friday of each week commencing from February 14, 2020, to April 10, 2020. At certain times or events such as when the government released major announcements or when there was a rapid increase in the number of infected individuals, a similar survey was conducted on an additional 1,200 individuals per week. Results A total of 12 surveys, including weekly surveys spanning over nine weeks, were conducted; a total of 19,113 samples from 12,254 individuals were obtained. The mean price for a hypothetical prophylactic vaccine was 2876.3 JPY (26.9 USD) at the first survey and was significantly increased to 3357.4 JPY (31.4 USD) for the most recent survey (p<0.0001). The percentage of healthy individuals who were unwilling to pay for a hypothetical therapeutic drug at the onset of COVID-19 symptoms was higher in the young age group than in the elderly groups at all phases, indicating a low level of crisis awareness among some young individuals. On the other hand, the percentage of those willing to pay for more than the standard prophylaxis influenza vaccine remained almost the same in all age groups, and it also increased when COVID-19 infection was widespread. In the sub-analysis, femaleswho have childrenand married individuals tended to answer higher costs for prevention. Conclusions Changes in crisis awareness in all age groups were found to be associated with an increasing familiarity along with an increase in the number of locally infected individuals. Though the percentage of those who will not pay was higher in the young age group than in the elderly age group, the percentage of those who will pay more than the standard costs of influenza vaccine or treatment drugs was the same between each aging group.