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We construct text-based measures of the primary concerns listed firms associated with the spread of COVID-19 and other epidemic diseases. We identify which firms perceive to lose or gain from a given epidemic and textually decompose the epidemic's effect on the firm's demand and supply. We find that the effects of COVID-19 manifest as a simultaneous shock to demand and supply, with both shocks affecting firms' market valuations in equal measure on average. By contrast, demand-related impacts appear more important in accounting for the observed collapse in firm-level investment during the COVID-19 crisis. Authors have furnished an Internet Appendix , which is available on the Oxford University Press Web site next to the link to the final published paper online [ABSTRACT FROM AUTHOR]

The CRISPR-Cas13 system has been proposed as an alternative treatment of viral infections. However, for this approach to be adopted as an antiviral, it must be optimized until levels of efficacy rival or exceed the performance of conventional approaches. To take steps toward this goal, we evaluated the influenza viral RNA degradation patterns resulting from the binding and enzymatic activity of mRNA-encoded LbuCas13a and two crRNAs from a prior study, targeting PB2 genomic and messenger RNA. We found that the genome targeting guide has the potential for significantly higher potency than originally detected, because degradation of the genomic RNA is not uniform across the PB2 segment, but it is augmented in proximity to the Cas13 binding site. The PB2 genome targeting guide exhibited high levels (>1 log) of RNA degradation when delivered 24 hours post-infection in vitro and maintained that level of degradation over time, with increasing multiplicity of infection (MOI), and across modern influenza H1N1 and H3N2 strains. Chemical modifications to guides with potent LbuCas13a function, resulted in nebulizer delivered efficacy (>1–2 log reduction in viral titer) in a hamster model of influenza (Influenza A/H1N1/California/04/09) infection given prophylactically or as a treatment (post-infection). Maximum efficacy was achieved with two doses, when administered both pre- and post-infection. This work provides evidence that mRNA-encoded Cas13a can effectively mitigate Influenza A infections opening the door to the development of a programmable approach to treating multiple respiratory infections. Author summary: For the CRISPR-Cas13 system to be adopted as an alternative treatment of viral infections, it must reach levels of efficacy that rival or exceed the performance of conventional approaches. We evaluated the degradation patterns resulting from the binding and enzymatic activity of mRNA-encoded LbuCas13a and two previously identified crRNAs, targeting conserved PB2 genomic and messenger RNA sequences. The genome targeting guide displayed higher potency than originally detected, because RNA degradation was augmented near the guide binding site, leading to 1-log of RNA degradation in vitro, which persisted over time, with increasing multiplicity of infection (MOI), and across modern influenza H1N1 and H3N2 strains. The addition of chemical modifications to the guide resulted in 1-2-log reduction in viral titer upon nebulizer delivery prophylactically or as a treatment in a hamster model of influenza. Maximum efficacy was achieved with two doses administered pre- and post-infection. [ABSTRACT FROM AUTHOR]

Surprisingly, the 1977 "Russian flu" H1N1 pandemic influenza virus was genetically indistinguishable from strains that had circulated decades earlier but had gone extinct in 1957. This essay puts forward the most plausible chronology to explain the reemergence of the 1977 H1N1 pandemic virus: (1) in January–February 1976, a self-limited small outbreak of a swine H1N1 influenza virus occurred among Army personnel at Fort Dix, New Jersey; (2) in March 1976, the US launched a nationwide H1N1 swine influenza vaccine program; (3) other countries then also launched their own H1N1 R&D efforts; (4) a new H1N1 outbreak, genetically unrelated to the Fort Dix swine virus but indistinguishable from previously extinct H1N1 viruses, was detected early in 1977 in China; (5) the leading Chinese influenza virologist later disclosed that the Chinese military had conducted large H1N1 vaccine R&D studies in 1976. It is likely that the resurrected H1N1 influenza viruses were laboratory-stored strains that were unfrozen and studied as part of the emergency response to a perceived epidemic threat, and that accidentally escaped. The fear of a possible H1N1 pandemic was the critical factor that gave rise to the actual H1N1 pandemic, resulting in an avoidable "self-fulfilling prophecy pandemic." [ABSTRACT FROM AUTHOR]

Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory responses that aim to contain and eliminate microbial invaders. Various lipid mediators (LMs) are biosynthesized and play a critical role in fighting viruses during inflammation; thus, by profiling the LMs in patients, researchers can obtain mechanistic insights into diseases, such as the pathways disrupted. To date, the relationship between molecular alterations in LMs and the pathogenesis of H1N1 influenza in children is poorly understood. Here, we employed a targeted liquid chromatography coupled with tandem mass spectrometry (LC‒MS/MS) to profile LMs in serum from children with H1N1 influenza (H1N1 children) and recovered children. We found that 22 LM species were altered in H1N1 children with mild symptoms. Analysis of the LM profiles of recovered children revealed a decrease in the levels of thromboxane B2 (TxB2) and thromboxane B3 (TxB3) and an increase in the levels of other 8 altered LM species associated with H1N1 influenza, including cytochrome P450 (CYP) enzyme-derived dihydroxyeicosatrienoic acids (DiHETrEs) and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid (AA), and epoxyoctadecamonoenoic acids (EpOMEs) from linoleic acid (LA). Taken together, the results of this study revealed that serum LMs change dynamically in H1N1 children with mild symptoms. The dramatically altered LMs in H1N1 children could serve as a basis for potential therapeutics or adjuvants against H1N1 influenza. [ABSTRACT FROM AUTHOR]

The influenza vaccines currently approved for clinical use mainly include inactivated influenza virus vaccines and live attenuated influenza vaccines (LAIVs). LAIVs have multiple advantages, such as ease of use and strong immunogenicity, and can provide cross-protection. In this study, the M gene of the PR8 virus was mutated as follows (G11T, C79G, G82C, C85G, and C1016A), and a live attenuated influenza virus containing the mutated M gene was rescued and obtained using reverse genetic technology as a vaccine candidate. The replication ability of the rescued virus was significantly weakened in both MDCK cells and mice with attenuated virulence. Studies on immunogenicity found that 1000 TCID50 of mutated PR8 (mPR8) can prime strong humoral and cellular immune responses. Single-dose immunization of 1000 TCID50 mPR8 was not only able to counter the challenge of the homologous PR8 virus but also provided cross-protection against the heterologous H9N2 virus. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. [ABSTRACT FROM AUTHOR]

Background: The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza. Methodology: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 μg or 7.5 μg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a computer program to create a randomization scheme with a block size of 3. Post-treatment follow-up was approximately 180 days. Primary safety outcomes included the incidence of study product related serious adverse events and unsolicited events within 180 days, solicited application site and systemic reactogenicity through 7 days after administration and solicited application site erythema and/or pigmentation 14, 28, 56 and 180 days after administration. Immunogenicity outcomes included antibody titers and percentage of seroconversion (SCR) and seroprotection (SPR) rates determined by the hemagglutination inhibition (HAI) assay. Exploratory outcomes included virus microneutralization (MN) titers, durability and breadth of the immune response. The trial was registered with ClinicalTrials.gov, number NCT 06125717. Findings: Between July 7, 2022 and March 13, 2023 45 participants were randomized to a treatment group. One participant was lost to follow up in the 15 μg group and 1 participant withdrew from the 7.5 μg dose group. Safety analyses included n = 15 per group, immunogenicity analyses included n = 14 for the 15 μg and 7.5 μg treatment groups and n = 15 for the placebo group. No SAEs were reported in any of the treatment groups. All treatment groups reported solicited local events within 7 days after vaccination, with mild (Grade 1) erythema being the most frequent symptom reported. Other local symptoms reported included mostly mild (Grade 1) induration/swelling, itching, pigmentation, skin flaking, and tenderness. Within 7 days after vaccination, 2 participants (4.4%) reported moderate (Grade 2) erythema, 1 participant (2.2%) reported moderate (Grade 2) induration/swelling, and 1 participant (2.2%) reported moderate (Grade 2) itching. There was an overall reduction in erythema and pigmentation reported on Days 15, 29, 57, and 180 among all treatment groups. Systemic symptoms reported within 7 days after vaccination, included mild (Grade 1) fatigue reported among all treatment groups, and mild (Grade 1) headache reported by 1 participant in the 7.5 μg treatment group. No study drug related severe symptoms were reported in the study. Group mean fold rises in HAI titers ranged between 8.7 and 12-fold, SCRs were >76% and SPRs were >92% for both VX-103 dose groups thereby fulfilling serological criteria established by the EMA and FDA for seasonal influenza vaccines. Longitudinal assessments demonstrate persistence of the immune response through at least Day 180. Conclusions: The MIMIX MAP platform is safe, well tolerated and elicits robust antibody responses. [ABSTRACT FROM AUTHOR]

Background: H1N1 is one of the major subtypes of influenza A virus (IAV) that causes seasonal influenza, posing a serious threat to human health. A traditional Chinese medicine combination called Qingxing granules (QX) is utilized clinically to treat epidemic influenza. However, its chemical components are complex, and the potential pharmacological mechanisms are still unknown. Methods: QX's effective components were gathered from the TCMSP database based on two criteria: drug-likeness (DL ≥ 0.18) and oral bioavailability (OB ≥ 30%). SwissADME was used to predict potential targets of effective components, and Cytoscape was used to create a "Herb-Component-Target" network for QX. In addition, targets associated with H1N1 were gathered from the databases GeneCards, OMIM, and GEO. Targets associated with autophagy were retrieved from the KEGG, HAMdb, and HADb databases. Intersection targets for QX, H1N1 influenza, and autophagy were identified using Venn diagrams. Afterward, key targets were screened using Cytoscape's protein–protein interaction networks built using the database STRING. Biological functions and signaling pathways of overlapping targets were observed through GO analysis and KEGG enrichment analysis. The main chemical components of QX were determined by high-performance liquid chromatography (HPLC), followed by molecular docking. Finally, the mechanism of QX in treating H1N1 was validated through animal experiments. Results: A total of 786 potential targets and 91 effective components of QX were identified. There were 5420 targets related to H1N1 and 821 autophagy-related targets. The intersection of all targets of QX, H1N1, and autophagy yielded 75 intersecting targets. Ultimately, 10 core targets were selected: BCL2, CASP3, NFKB1, MTOR, JUN, TNF, HSP90AA1, EGFR, HIF1A, and MAPK3. Identification of the main chemical components of QX by HPLC resulted in the separation of seven marker ingredients within 195 min, which are amygdalin, puerarin, baicalin, phillyrin, wogonoside, baicalein, and wogonin. Molecular docking results showed that BCL2, CASP3, NFKB1, and MTOR could bind well with the compounds. In animal studies, QX reduced the degenerative alterations in the lung tissue of H1N1-infected mice by upregulating the expression of p-mTOR/mTOR and p62 and downregulating the expression of LC3, which inhibited autophagy. Conclusions: According to this study's network pharmacology analysis and experimental confirmation, QX may be able to treat H1N1 infection by regulating autophagy, lowering the expression of LC3, and increasing the expression of p62 and p-mTOR/mTOR. [ABSTRACT FROM AUTHOR]

Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two‐sample Mendelian randomization analysis. Based on the data from our in‐house genome‐wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303–143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, β = −3.212, p = 0.019), low‐density‐lipoprotein cholesterol (LDL‐C, β = −1.372, p = 0.045), and basophil counts (Baso, β = −1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL‐C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory tract infections (RTIs) stand out as the most frequent causes leading to visits to the emergency department and hospitalizations. This study aims to assess the types and prevalence of respiratory infections across two years following the end of the COVID-19 pandemic. Methods: Patients presenting with an influenza-like illness (ILI) were tested using multiplex RT-PCR (QIAstat-Dx, Qiagen). The multiplexed RT- PCR test detects 21 respiratory viruses and bacteria. Results: During the study period, PCR test was done on a total of 1,790 samples were tested, and 712 (40%) were positive for a total of 796 pathogens. The mean age (± SD) of the participants was 20.1 ± 28.4 years in 2022 and 21.9 ± 27.6 years in 2023. Among the detected pathogens, the most prevalent were Rhinovirus/Enterovirus 222 (12.4%), followed by RSV A&B (103 cases, 5.7%), and H1N1 Influenza (77 cases, 4.3%). Additionally, Influenza A/B constituted 172 (9.6%) while parainfluenza constituted (58, 3.2%). SARS-CoV-2 was identified in 3.97% of the samples. Over the two-year period, the monthly pattern of the identified pathogens exhibited fluctuations in the prevalence. Furthermore, variations were observed in the detected pathogens across different age groups. Conclusion: In addition to adding significant knowledge to the field of respiratory viral infections, this study emphasizes the necessity of ongoing research and surveillance for the detection and characterization of respiratory viruses, particularly those with the potential for emergence. Such studies would also require setting up a strategy for genotyping and/or sequencing of viruses. [ABSTRACT FROM AUTHOR]

Onradivir (ZSP1273) is a novel anti-influenza A virus inhibitor. Preclinical studies show that onradivir can inhibit influenza A H1N1 and H3N2 replication and increase the survival rate of infected animals. In this study, we aimed to evaluate the safety and efficacy of three onradivir dosing regimens versus placebo in outpatients with acute uncomplicated influenza A virus infection. We did a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial at 20 clinical sites in China. Eligible participants were adults (18–65 years) with an influenza-like illness screened by rapid antigen testing at the first clinical visit, had the presence of a fever (axillary temperature ≥38·0°C), and had the presence of at least one moderate systemic and one respiratory symptom within 48 h of symptom onset. Patients were excluded if they were pregnant, allergic to onradivir, or had received any influenza antiviral medication within 7 days before enrolment. Participants were randomly assigned (1:1:1:1) into four groups by an interactive web response system: onradivir 200 mg twice per day group, onradivir 400 mg twice per day group, onradivir 600 mg once per day group, and a matching placebo group. A 5-day oral treatment course was initiated within 48 h after symptoms onset. The primary outcome was the time to alleviate influenza symptoms in the modified intention-to-treat population. Safety was a secondary outcome. We evaluated the patients' self-assessed severity of seven influenza symptoms on a 4-point ordinal scale, and the treatment-emergent adverse events in all patients. This trial is registered with ClinicalTrials.gov , number NCT04024137. Between Dec 7, 2019, and May 18, 2020, a total of 205 patients were screened; of whom, 172 (84%) were randomly assigned to receive onradivir (n=43 in the 200 mg twice per day group; n=43 in the 400 mg twice per day group; and n=43 in the 600 mg once per day group), or placebo (n=42). Median age was 22 years (IQR 20–26). All three onradivir groups showed decreased median time to alleviate influenza symptoms (46·92 h [IQR 24·00–81·38] in the 200 mg twice per day group, 54·87 h [23·67–110·62] in the 400 mg twice per day group, and 40·05 h [17·70–65·82] in the 600 mg once per day) compared with the placebo group (62·87 h [36·40–113·25]). The median difference between the onradivir 600 mg once per day group and the placebo group was –22·82 h (p=0·0330). The most frequently reported treatment-emergent adverse event was diarrhoea (71 [42%] of 171), ranging from 33–65% of the patients in onradivir-treated groups compared with 10% in the placebo group; no serious adverse events were observed. Onradivir showed a safety profile comparable to placebo, as well as higher efficacy than placebo in ameliorating influenza symptoms and lowering the viral load in adult patients with uncomplicated influenza infection, especially the onradivir 600 mg once per day regimen. National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, National Natural Science Foundation of China, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project, Emergency Key Program of Guangzhou Laboratory, Macao Science and Technology Development Fund, and Guangdong Raynovent Biotech. [ABSTRACT FROM AUTHOR]

The H1N1pdm09 virus has been a persistent threat to public health since the 2009 pandemic. Particularly, since the relaxation of COVID‐19 pandemic mitigation measures, the influenza virus and SARS‐CoV‐2 have been concurrently prevalent worldwide. To determine the antigenic evolution pattern of H1N1pdm09 and develop preventive countermeasures, we collected influenza sequence data and immunological data to establish a new antigenic evolution analysis framework. A machine learning model (XGBoost, accuracy = 0.86, area under the receiver operating characteristic curve = 0.89) was constructed using epitopes, physicochemical properties, receptor binding sites, and glycosylation sites as features to predict the antigenic similarity relationships between influenza strains. An antigenic correlation network was constructed, and the Markov clustering algorithm was used to identify antigenic clusters. Subsequently, the antigenic evolution pattern of H1N1pdm09 was analyzed at the global and regional scales across three continents. We found that H1N1pdm09 evolved into around five antigenic clusters between 2009 and 2023 and that their antigenic evolution trajectories were characterized by cocirculation of multiple clusters, low‐level persistence of former dominant clusters, and local heterogeneity of cluster circulations. Furthermore, compared with the seasonal H1N1 virus, the potential cluster‐transition determining sites of H1N1pdm09 were restricted to epitopes Sa and Sb. This study demonstrated the effectiveness of machine learning methods for characterizing antigenic evolution of viruses, developed a specific model to rapidly identify H1N1pdm09 antigenic variants, and elucidated their evolutionary patterns. Our findings may provide valuable support for the implementation of effective surveillance strategies and targeted prevention efforts to mitigate the impact of H1N1pdm09. [ABSTRACT FROM AUTHOR]

This article explores the potential drawbacks of increased regulation of laboratory-developed tests (LDTs) and challenges the assumption that more regulation automatically leads to better quality. It argues that excessive regulation could actually pose a greater risk to the quality of LDTs and highlights instances where LDTs have performed favorably compared to FDA-cleared tests. The article emphasizes the advantages of LDTs, such as their ability to quickly adapt to changing needs. It concludes that increased regulation may have negative effects on test quality, innovation, and access to tests for uncommon conditions or limited markets. The article also references three other articles that discuss topics related to laboratory testing, including the use of quantitative hCG immunoassays as tumor markers, the laboratory diagnosis of the 2009 H1N1 influenza A virus, and the interference of biotin in laboratory tests. These additional articles may be of interest to library patrons researching these specific topics. [Extracted from the article]

Background: Extracorporeal membrane oxygenation (ECMO) is a cutting-edge life-support measure for patients with severe cardiac and pulmonary illnesses. Although there are several systematic reviews (SRs) about ECMO, it remains to be seen how quality they are and how efficacy and safe the information about ECMO they describe is in these SRs. Therefore, performing an overview of available SRs concerning ECMO is crucial. Methods: We searched four electronic databases from inception to January 2023 to identify SRs with or without meta-analyses. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were used to assess the methodological quality, and evidence quality for SRs, respectively. A bubble plot was used to visually display clinical topics, literature size, number of SRs, evidence quality, and an overall estimate of efficacy. Results: A total of 17 SRs met eligibility criteria, which were combined into 9 different clinical topics. The methodological quality of the included SRs in this mapping was "Critically low" to "Moderate". One of the SRs was high-quality evidence, three on moderate, three on low, and two on very low-quality evidence. The most prevalent study used to evaluate ECMO technology was observational or cohort study with frequently small sample sizes. ECMO has been proven beneficial for severe ARDS and ALI due to the H1N1 influenza infection. For ARDS, ALF or ACLF, and cardiac arrest were concluded to be probably beneficial. For dependent ARDS, ARF, ARF due to the H1N1 influenza pandemic, and cardiac arrest of cardiac origin came to an inconclusive conclusion. There was no evidence for a harmful association between ECMO and the range of clinical topics. Conclusions: There is limited available evidence for ECMO that large sample, multi-center, and multinational RCTs are needed. Most clinical topics are reported as beneficial or probably beneficial of SRs for ECMO. Evidence mapping is a valuable and reliable methodology to identify and present the existing evidence about therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission. [ABSTRACT FROM AUTHOR]

It is hypothesized that narcolepsy type 1 (NT1) develops in genetically susceptible people who encounter environmental triggers leading to immune-mediated hypocretin-1 deficiency. The pathophysiologies of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) remain unknown. The main aim of this study was to collect all reported immunological events before onset of a central disorder of hypersomnolence. Medical records of 290 people with NT1, and 115 with NT2 or IH were retrospectively reviewed to extract infection and influenza vaccination history. Prevalence, distribution of immunological events, and time until hypersomnolence onset were compared between NT1 and the combined group of NT2 and IH. Immunological events were frequently reported before hypersomnolence disorder onset across groups. Flu and H1N1 influenza vaccination were more common in NT1, and Epstein–Barr virus and other respiratory and non-respiratory infections in NT2 and IH. Distributions of events were comparable between NT2 and IH. Rapid symptom onset within one month of infection was frequent across groups, especially after flu infection in NT1. Hypersomnolence disorder progression after an immunological event was reported in ten individuals. Our findings suggest a variety of immunological triggers potentially related to NT1, including H1N1 influenza infection or vaccination, infection with other flu types, and other respiratory and non-respiratory infections. Frequent reports of immunological events (other than those reported in NT1) immediately prior to the development of NT2 and IH support the specificity of triggers for NT1, and open important new research avenues into possible underlying immunological mechanisms in NT2 and IH. • We studied possible immunological triggers for central disorders of hypersomnolence. • Flu and H1N1 influenza vaccination were more common before narcolepsy type 1 onset. • Non-flu infections were common before narcolepsy type 2/idiopathic hypersomnia onset. • Rapid hypersomnolence onset within one month was frequent across groups. [ABSTRACT FROM AUTHOR]

Pyrogallol, a natural polyphenol compound (1,2,3‐trihydroxybenzene), has shown efficacy in the therapeutic treatment of disorders associated with inflammation. Nevertheless, the mechanisms underlying the protective properties of pyrogallol against influenza A virus infection are not yet established. We established in this study that pyrogallol effectively alleviated H1N1 influenza A virus‐induced lung injury and reduced mortality. Treatment with pyrogallol was found to promote the expression and nuclear translocation of nuclear factor erythroid‐2‐related factor 2 (Nrf2) and peroxisome proliferator‐activated receptor gamma (PPAR‐γ). Notably, the activation of Nrf2 by pyrogallol was involved in elevating the expression of PPAR‐γ, both of which act synergistically to enhance heme oxygenase‐1 (HO‐1) synthesis. Blocking HO‐1 by zinc protoporphyrin (ZnPP) reduced the suppressive impact of pyrogallol on H1N1 virus‐mediated aberrant retinoic acid‐inducible gene‐I‐nuclear factor kappa B (RIG‐I–NF‐κB) signaling, which thus abolished the dampening effects of pyrogallol on excessive proinflammatory mediators and cell death (including apoptosis, necrosis, and ferroptosis). Furthermore, the HO‐1‐independent inactivation of janus kinase 1/signal transducers and activators of transcription (JAK1/STATs) and the HO‐1‐dependent RIG‐I‐augmented STAT1/2 activation were both abrogated by pyrogallol, resulting in suppression of the enhanced transcriptional activity of interferon‐stimulated gene factor 3 (ISGF3) complexes, thus prominently inhibiting the amplification of the H1N1 virus‐induced proinflammatory reaction and apoptosis in interferon‐beta (IFN‐β)‐sensitized cells. The study provides evidence that pyrogallol alleviates excessive proinflammatory responses and abnormal cell death via HO‐1 induction, suggesting it could be a potential agent for treating influenza. [ABSTRACT FROM AUTHOR]

The article addresses the need to enhance T cell-based strategies to counteract the H3N2 influenza virus, highlighting their potential as universal preventive measures. Topics discussed include the challenges of accurate diagnosis and effective vaccination, the critical role of T cells in combating influenza, and the need for further research and standardized methods to optimize T cell vaccine efficacy.

Background: The implementation of mRNA vaccines against COVID-19 has successfully validated the safety and efficacy of the platform, while at the same time revealing the potential for their applications against other infectious diseases. Traditional seasonal influenza vaccines often induce strain specific antibody responses that offer limited protection against antigenically drifted viruses, leading to reduced vaccine efficacy. Modern advances in viral surveillance and sequencing have led to the development of in-silico methodologies for generating computationally optimized broadly reactive antigens (COBRAs) to improve seasonal influenza vaccines. Methods: In this study, immunologically naïve mice were intramuscularly vaccinated with mRNA encoding H1 and H3 COBRA hemagglutinins (HA) or wild-type (WT) influenza HAs encapsulated in lipid nanoparticles (LNPs). Results: Mice vaccinated with H1 and H3 COBRA HA-encoding mRNA vaccines generated robust neutralizing serum antibody responses against more antigenically distinct contemporary and future drifted H1N1 and H3N2 influenza strains than those vaccinated with WT H1 and H3 HA-encoding mRNA vaccines. The H1 and H3 COBRA HA-encoding mRNA vaccines also prevented influenza illness, including severe disease in the mouse model against H1N1 and H3N2 viruses. Conclusions: This study highlights the potential benefits of combining universal influenza antigen design technology with modern vaccine delivery platforms and exhibits how these vaccines can be advantageous over traditional WT vaccine antigens at eliciting superior protective antibody responses against a broader number of influenza virus isolates. [ABSTRACT FROM AUTHOR]

This paper reports a case of influenza complicated with influenza associated encephalopathy complicated with acute pancreatitis. This kind of disease is relatively rare, we hope to draw people's attention to it in order to improve early detection and prognosis. [ABSTRACT FROM AUTHOR]

Allobetulin derivatives with rearranged E-ring exhibit important pharmacological properties against various viral pathogens. Basing on 3β-acetoxy-21β-acetyl-20β,28-epoxy-18α,19βH-ursane triterpenoid, obtained from allobetulin in one stage, a series of new derivatives have been synthesized and their antiviral activity against both influenza virus A (H1N1) and SARS-CoV-2 pseudovirus was evaluated. Among them, 2,3-indolo-allobetulone N-propargyl derivatives were the most efficacious against influenza virus with low toxicity (CC50 × 300 μM) and IC50 values of 7.04 to 3.5 μM and high selectivity indexes (SI 43 and 86). Compared with amodiaquine, a derivative with 3-pyridinylidene fragment 12 showed a weak antiviral activity against SARS-CoV-2 pseudovirus with an inhibition rate of 57.3% at a concentration of 20 μM. Further optimization to increase the cellular antiviral activity seems to be necessary to develop this series of triterpenoids as antiviral agents. [ABSTRACT FROM AUTHOR]

Influenza remains one of the most serious infectious diseases. Gallic acid is one of the most common and representative phenolic acids found in various plants. This is an interesting subject to explore how gallic acid could inhibit H1N1 influenza virus infection by reducing the production of virulent proteins and interrupting autophagy machinery for influenza virus replication on the host cell. Cellular viability was assessed by XTT assay. The inhibitory effects on the H1N1 influenza virus were assessed by hemagglutination assay, plaque assay, and qRT‐PCR. Western blot analysis was used for detecting protein levels of M1, M2, NP, LC3B, and beclin‐1. Autophagy activity was demonstrated by acridine orange staining assay. The result demonstrated that there was no cytotoxic effect of gallic acid on A549 cells, and gallic acid could restore the cellular viability of H1N1 influenza virus‐infected A549 cells within the experimental concentration treatment. Moreover, gallic acid could effectively restrain viral activity of the H1N1 influenza virus. After the treatment of gallic acid, the production of virulent H1N1 influenza virus proteins, that is, M1, M2, and NP protein were reduced. As for autophagic mechanism, both of the LC3B II conversion and the level ratio of LC3B II to LC3B I were notably decreased. The acridine orange staining assay also revealed decreased accumulation of autophagosomes in H1N1 influenza virus‐infected cells. In conclusion, gallic acid suppresses H1N1 influenza viral infectivity through restoration of autophagy pathway and inhibition of virulent M1, M2, and NP protein production. [ABSTRACT FROM AUTHOR]

The increased detection of H3 C-IVA (1990.4.a) clade influenza A viruses (IAVs) in US swine in 2019 was associated with a reassortment event to acquire an H1N1pdm09 lineage nucleoprotein (pdmNP) gene, replacing a TRIG lineage NP (trigNP). We hypothesized that acquiring the pdmNP conferred a selective advantage over prior circulating H3 viruses with a trigNP. To investigate the role of NP reassortment in transmission, we identified two contemporary 1990.4.a representative strains (NC/19 and MN/18) with different evolutionary origins of the NP gene. A reverse genetics system was used to generate wild-type (wt) strains and swap the pdm and TRIG lineage NP genes, generating four viruses: wtNC/19-pdmNP, NC/19-trigNP, wtMN/18-trigNP, and MN/18-pdmNP. The pathogenicity and transmission of the four viruses were compared in pigs. All four viruses infected 10 primary pigs and transmitted to five indirect contact pigs per group. Pigs infected via contact with MN/18-pdmNP shed virus 2 days earlier than pigs infected with wtMN/18-trigNP. The inverse did not occur for wtNC/19-pdmNP and NC/19-trigNP. This suggests that pdmNP reassortment resulted in a combination of genes that improved transmission efficiency when paired with the 1990.4.a hemagglutinin (HA). This is likely a multigenic trait, as replacing the trigNP gene did not diminish the transmission of a wild-type IAV in swine. This study demonstrates how reassortment and evolutionary change of internal genes can result in more transmissible viruses that influence HA clade detection frequency. Thus, rapidly identifying novel reassortants paired with dominant hemagglutinin/neuraminidase may improve the prediction of strains to include in vaccines. [ABSTRACT FROM AUTHOR]

The Influenza A H1N1 subtype can present with a wide spectrum of severity, from mild symptoms of influenza to severe respiratory distress. The morbidity and mortality connected to influenza are mostly associated with secondary bacterial infections. The influenza syndrome alone can cause a massive release of cytokines with dysregulation of the immune system, and it can act in synergy with other bacteria which can enhance cytokines secretion. This article deals with a case of severe pneumonia of H1N1 in a 17-year-old woman with bacterial superinfection with Staphylococcus aureus characterized by a high level of interleukine-6 (105900 pg/mL) and the appearance of severe leukopenia with immuno-suppression, such that HIV infection and hematological diseases were included in the initial differential diagnosis. After death, the autopsy confirmed the presence of severe pneumonia, in addition to an hepatic steatosis in absence of other risk factors. This case reports the rapid and lethal course of influenza A / H1N1 in a young and healthy subject without co-morbidities, in an age group in which mortality is about 0.3 deaths per 100,000. The case underlines the importance of quickly diagnosis of viral infections and the differential diagnoses with other immunosuppressive diseases, which can be fatal even in adolescent and healthy subjects. [ABSTRACT FROM AUTHOR]

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates. [ABSTRACT FROM AUTHOR]

The mortality of patients with severe pneumonia caused by infection is closely related to viral replication H1N1 and cytokine storm. However, the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated. Here, we identified hypoxia inducible factor-1α (HIF-1α) as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells. Specifically, HIF-1α protein expression is upregulated after H1N1 infection. Deficiency of HIF-1α attenuates pulmonary injury, viral replication and cytokine storm in vivo. In addition, viral replication and cytokine storm were inhibited after HIF-1α knockdown in vitro. Mechanistically, the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis, with rapid production of ATP and lactate. Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses. Further analysis revealed that H1N1-induced HIF-1α can promote the expression of hexokinase 2 (HK2), the key enzyme of glycolysis, and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate, which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/β production. In conclusion, this study demonstrated that the upregulation of HIF-1α by H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2, providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection. [ABSTRACT FROM AUTHOR]

The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century. In this study, we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients. Sequence comparison of the three main protein subunits (PB2, PB1, and PA) of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution (E206K) was responsible for the observed impaired replication phenotype. Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/ WSN/33 virus in mammalian cells and a reduction in the virus's pathogenicity in vivo. Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1-PA complex to the nucleus at high temperature (39.5 °C). Hence, this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines. [ABSTRACT FROM AUTHOR]

Background: Despite their higher risk of developing severe disease, little is known about the burden of influenza in Portugal in children aged < 5 years old. This study aims to cover this gap by estimating the clinical and economic burden of severe influenza in children, in Portugal, during ten consecutive influenza seasons (2008/09-2017/18). Methods: We reviewed hospitalizations in children aged < 5 years old using anonymized administrative data covering all public hospitals discharges in mainland Portugal. The burden of hospitalization and in-hospital mortality directly coded as due to influenza was supplemented by the indirect burden calculated from excess hospitalization and mortality (influenza-associated), estimated for four groups of diagnoses (pneumonia or influenza, respiratory, respiratory or cardiovascular, and all-cause), through cyclic regression models integrating the incidence of influenza. Means were reported excluding the H1N1pdm09 pandemic (2009/10). Results: The mean annual number of hospitalizations coded as due to influenza was 189 (41.3 cases per 100,000 children aged < 5 years old). Hospitalization rates decreased with increasing age. Nine-in-ten children were previously healthy, but the presence of comorbidities increased with age. Children stayed, on average, 6.1 days at the hospital. Invasive mechanical ventilation was used in 2.4% of hospitalizations and non-invasive in 3.1%. Influenza-associated excess hospitalizations between 2008 and 2018 were estimated at 1,850 in pneumonia or influenza, 1,760 in respiratory, 1,787 in respiratory or cardiovascular, and 1,879 in all-cause models. A total of 95 influenza-associated excess deaths were estimated in all-cause, 14 in respiratory or cardiovascular, and 9 in respiratory models. Over ten years, influenza hospitalizations were estimated to have cost the National Health Service at least €2.9 million, of which 66.5% from healthy children. Conclusions: Influenza viruses led to a high number of hospitalizations in children. Most were previously healthy. Results should lead to a reflection on the adequate preventive measures to protect this age group. [ABSTRACT FROM AUTHOR]

Influenza pandemic with H1N1 (H1N1pdms) causes severe lung damage and "cytokine storm," leading to higher mortality and global health emergencies in humans and animals. Explaining host antiviral molecular mechanisms in response to H1N1pdms is important for the development of novel therapies. In this study, we organised and analysed multimicroarray data for mouse lungs infected with different H1N1pdm and nonpandemic H1N1 strains. We found that H1N1pdms infection resulted in a large proportion of differentially expressed genes (DEGs) in the infected lungs compared with normal lungs, and the number of DEGs increased markedly with the time of infection. In addition, we found that different H1N1pdm strains induced similarly innate immune responses and the identified DEGs during H1N1pdms infection were functionally concentrated in defence response to virus, cytokine-mediated signalling pathway, regulation of innate immune response, and response to interferon. Moreover, comparing with nonpandemic H1N1, we identified ten distinct DEGs (AREG, CXCL13, GATM, GPR171, IFI35, IFI47, IFIT3, ORM1, RETNLA, and UBD), which were enriched in immune response and cell surface receptor signalling pathway as well as interacted with immune response-related dysregulated genes during H1N1pdms. Our discoveries will provide comprehensive insights into host responding to pandemic with influenza H1N1 and find broad-spectrum effective treatment. [ABSTRACT FROM AUTHOR]

This article analyzes in a general way the relationship between the origin of the COVID-19 pandemic and industrial (mass production) animal husbandry farms (wild and domestic). The fact that the origin of SARS-CoV-2, the coronavirus that causes COVID-19 disease, has not been conclusively determined, and even though the WHO has preferentially considered the animal origin (zoonotic hypothesis), ruling out the hypothesis of the escape of the coronavirus in a laboratory, there are aspects that due to the previous history of influenza pandemics (2003 H5NI avian influenza and 2009 H1N1 swine influenza) raise the need to review the role played by transnational companies in the food chain, as well as the strategies of these companies to shape regulations in this area at their convenience. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) disease burden is significant among children; however, RSV can also cause excess morbidity and mortality among older adults. Populations in long-term care homes (LTCHs) may be at greater risk of exposure and increased infection severity. The objectives of this article are to identify evidence regarding disease burden and outcome severity attributable to RSV outbreaks among residents and staff in LTCHs; and to highlight reported population and outbreak characteristics. Methods: All types of evidence were eligible for inclusion. Data utilized by included studies was between the end of the 2010 H1N1 influenza pandemic and the beginning of the coronavirus disease 2019 (COVID-19) pandemic. Evidence from the following countries was considered: G7, the European Union, Australia and New Zealand. A total of 167 articles were identified; 58 full texts were analyzed and four sources of evidence were eligible for inclusion. Data related to population characteristics, outbreak type and resident and staff outcomes were manually charted. Results: There is a paucity of evidence sources pertaining to RSV outbreak burden among residents and staff in LTCHs. Outbreak duration ranged from 13 to 21 days. For each outbreak, 4-7 residents had confirmed RSV infection. Attack rates ranged from 12% to 38%. A spectrum of disease attributable to RSV outbreaks in LTCHs was identified, ranging from mild cold-like symptoms to death. Conclusion: Integration of RSV into existing respiratory pathogen surveillance programs is important to characterize susceptibility, transmissibility and virulence of RSV in at-risk populations. There is a need for public health organizations to publish the findings from outbreak investigations to provide evidence to inform RSV outbreak prevention and response in LTCH settings. [ABSTRACT FROM AUTHOR]

This article emphasizes the importance of threat agnostic epidemiology and surveillance in US public health agencies for ensuring health security. It discusses the need for investments in the applied epidemiology workforce, training, and public health data systems to implement new scientific technologies and methods. The article highlights various approaches to threat agnostic surveillance, including syndromic surveillance, electronic laboratory and case reporting, and wastewater surveillance. It also discusses the challenges and potential of home testing, genomic surveillance, and data modernization in public health practice. The article concludes by emphasizing the need for continued investment in public health data infrastructure to strengthen the nation's biodefense capacity and enhance health security. The document further discusses the importance of modernizing public health data systems and building capacity in the epidemiology workforce to effectively respond to future public health threats. It emphasizes the need for collaborative efforts and the adoption of standards to improve data exchange and interoperability. The document also highlights the gaps in the epidemiology workforce and the need for ongoing training and flexible funding models. It concludes by providing recommendations to support threat agnostic public health surveillance, including increasing diagnostic capabilities, developing methods for integrating non-traditional laboratory test results, and providing sustainable funding for data modernization and workforce development. [Extracted from the article]

This article examines the relationship between humans and artificial intelligence (AI) in decision-making. It discusses the use of AI in dating apps and argues that traditional methods can be just as effective. The limitations of AI in decision-making are highlighted, particularly in uncertain contexts. The article emphasizes the importance of transparency and accountability in AI systems and explores alternative decision-making methods. It also discusses the challenges of relying solely on data correlations and provides examples of failed AI applications. The concept of transparency in AI systems is discussed, along with the need for informed consent and privacy. The potential dangers of surveillance and surveillance capitalism are addressed, and the article suggests that transparency can empower users and foster dialogue. The idea of societal control through social media and "big nudging" in political campaigns is also explored. Ultimately, the article emphasizes the need for a balance between a smart world and individual freedoms. [Extracted from the article]

Background: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been demonstrated to be effective in treating patients with virus-induced acute respiratory distress syndrome (ARDS). However, whether the management of ECMO is different in treating H1N1 influenza and coronavirus disease 2019 (COVID-19)-associated ARDS patients remains unknown. Methods: This is a retrospective cohort study. We included 12 VV-ECMO-supported COVID-19 patients admitted to The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Eighth People's Hospital, and Wuhan Union Hospital West Campus between January 23 and March 31, 2020. We retrospectively included VV-ECMO-supported patients with COVID-19 and H1N1 influenza-associated ARDS. Clinical characteristics, respiratory mechanics including plateau pressure, driving pressure, mechanical power, ventilatory ratio (VR) and lung compliance, and outcomes were compared. Results: Data from 25 patients with COVID-19 (n=12) and H1N1 (n=13) associated ARDS who had received ECMO support were analyzed. COVID-19 patients were older than H1N1 influenza patients (P=0.004). The partial pressure of arterial carbon dioxide (PaCO2) and VR before ECMO initiation were significantly higher in COVID-19 patients than in H1N1 influenza patients (P

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain that has naturally high pathogenic properties in mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced. SA-M5 lost E358E/K heterogeneity and retained E358, which is the prevalent amino acid at this position among H1N1pdm09 strains. In addition, in the hemagglutinin of SA-M5, two heterogeneous substitutions (G155G/E and S190S/R) were identified. Both viruses, SA-M5 and SA-WT, were compared for their toxicity, ability to replicate, pathogenicity, and immunogenicity in mice. In mice infected with SA-M5 or SA-WT strains, toxicity, virus titer in pulmonary homogenates, and mouse survival did not differ significantly. In contrast, an increase in the immunogenicity of SA-M5 compared to SA-WT was observed. This increase could be due to the substitutions G155G/E and S190S/R in the HA of SA-M5. The prospects for using SA-M5 in studying the immunogenicity mechanisms were also discussed. [ABSTRACT FROM AUTHOR]

Influenza A viruses are RNA viruses that cause epidemics in humans and are enzootic in the pig population globally. In 2009, pig-to-human transmission of a reassortant H1N1 virus (H1N1pdm09) caused the first influenza pandemic of the 21st century. This study investigated the infection dynamics, pathogenesis, and lesions in pigs and ferrets inoculated with natural isolates of swine-adapted, human-adapted, and "pre-pandemic" H1N1pdm09 viruses. Additionally, the direct-contact and aerosol transmission properties of the three H1N1pdm09 isolates were assessed in ferrets. In pigs, inoculated ferrets, and ferrets infected by direct contact with inoculated ferrets, the pre-pandemic H1N1pdm09 virus induced an intermediary viral load, caused the most severe lesions, and had the highest clinical impact. The swine-adapted H1N1pdm09 virus induced the highest viral load, caused intermediary lesions, and had the least clinical impact in pigs. The human-adapted H1N1pdm09 virus induced the highest viral load, caused the mildest lesions, and had the least clinical impact in ferrets infected by direct contact. The discrepancy between viral load and clinical impact presumably reflects the importance of viral host adaptation. Interestingly, the swine-adapted H1N1pdm09 virus was transmitted by aerosols to two-thirds of the ferrets. Further work is needed to assess the risk of human-to-human aerosol transmission of swine-adapted H1N1pdm09 viruses. Author summary: Influenza A viruses (IAVs) have a high evolutionary rate and evolve through genetic drift and reassortment events, elevating their pandemic threat. The last pandemic caused by IAV was a consequence of a spillover of IAV from pigs to humans in 2009 (referred to as H1N1pdm09). The viral and host markers important for host adaptation of IAVs are poorly defined, which makes it difficult to evaluate the pandemic potential of novel swine IAV strains. A method of predicting the risk of human-to-human transmission of IAVs is by using the ferret as an animal model. In this study, we assessed the degree of host adaptation to pigs and ferrets of three different H1N1pdm09 viruses by virological, clinical, and pathological measures. We found that a swine-adapted H1N1pdm09 had the highest viral fitness but the lowest virulence in pigs and that a human-adapted H1N1pdm09 had the highest viral fitness but the lowest virulence in ferrets. In both animal models, we found that an H1N1pdm09 virus resembling a pre-pandemic variant had an intermediary viral fitness but the highest virulence. Our findings indicate that host adaptation is important for the viral fitness and virulence and that an increased viral fitness is not always related with a higher virulence. [ABSTRACT FROM AUTHOR]

In 2009, a novel H1N1 influenza virus caused the first influenza pandemic of the 21st century. Studies have shown that the influenza M gene played important roles in the pathogenicity and transmissibility of the 2009 H1N1 pandemic ((H1N1)pdm09), whilst the underlying mechanism remains unclear. The influenza M gene encodes two proteins, matrix protein 1 and matrix protein 2, which play important roles in viral replication and assembly. In this study, it is found that the M2 protein of the (H1N1)pdm09 virus showed a lower mobility rate than the North America triple-reassortant influenza M2 protein in Polyacrylamide Gel Electrophoresis (PAGE). The site-directed mutations of the amino acids of (H1N1)pdm09 M2 revealed that E79 is responsible for the mobility rate change. Further animal studies showed that the (H1N1)pdm09 containing a single M2-E79K was significantly attenuated compared with the wild-type virus in mice and induced lower proinflammatory cytokines and IFNs in mouse lungs. Further in vitro studies indicated that this mutation also affected NLRP3 inflammasome activation. To reveal the reason why they have different mobility rates, a circular dichroism spectra assay was employed and showed that the two M2 proteins displayed different secondary structures. Overall, our findings suggest that M2 E79 is important for the virus replication and pathogenicity of (H1N1)pdm09 through NLRP3 inflammasome and proinflammatory response. [ABSTRACT FROM AUTHOR]

The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reduced the viral load in SARS-CoV-2-infected individuals. Here, we evaluate the efficacy of azelastine-HCl against additional human coronaviruses, including the SARS-CoV-2 omicron variant and a seasonal human coronavirus, 229E, through in vitro infection assays, with azelastine showing a comparable potency against both. Furthermore, we determined that azelastine-HCl also inhibits the replication of Respiratory syncytial virus A (RSV A) in both prophylactic and therapeutic settings. In a human 3D nasal tissue model (MucilAirTM-Pool, Epithelix), azelastine-HCl protected tissue integrity and function from the effects of infection with influenza A H1N1 and resulted in a reduced viral load soon after infection. Our results suggest that azelastine-HCl has a broad antiviral effect and can be considered a safe option against the most common respiratory viruses to prevent or treat such infections locally in the form of a nasal spray that is commonly available globally. [ABSTRACT FROM AUTHOR]

Background: Disposable N95 respirator shortages during the COVID‐19 and 2009 H1N1 influenza pandemics highlighted the need for reusable alternatives, such as elastomeric half‐mask respirators (EHMRs). Two US medical organizations deployed reusable EHMRs during the COVID‐19 response. In addition to wipe‐based disinfection following patient care episodes expected per local policies at both organizations, postshift centralized cleaning and disinfection (C&D) was expected at one site (A), permitting shared‐pool EHMR use, and optional at the other (Site B), where EHMRs were issued to individuals. Using a survey, we evaluated disinfection practices reported by EHMR users and predictors of disinfection behaviors and perceptions. Methods: Surveys assessed EHMR disinfection practices, occupational characteristics, EHMR use frequency, training, and individual‐issue versus shared‐pool EHMR use. Results: Of 1080 EHMR users completing the survey, 76% reported that they disinfect the EHMR after each patient encounter, which was the expected practice at both sites. Increasing EHMR use, recall of disinfection training, and work in intensive care or emergency settings significantly influenced higher reporting of this practice. 36% of respondents reported using centralized C&D, although reporting was higher at the site (A) where this was expected (53%). Confidence in cleanliness of the EHMR following centralized C&D was not influenced by individual versus shared‐pool EHMR issue. Conclusions: Most EHMR users reported adherence with expected post‐care individual‐based disinfection of EHMRs but did not necessarily use standardized, centralized C&D. Future efforts to limit reliance on behavior related to respirator disinfection may improve EHMR implementation in healthcare to avert dependence on single‐use, disposable N95 respirators. [ABSTRACT FROM AUTHOR]

Assaying the potency of inactivated viral influenza vaccines is performed using single radial immunodiffusion, which is the globally accepted release method for potency. Under conditions of a rapidly emerging pandemic, such as the 2009 H1N1 influenza pandemic, a recognized obstacle in the delivery of vaccines to the public is the time needed for the distribution of calibrated SRID reagents (antisera and antigen standards) to vaccine manufacturers. Previously, we first described a novel streamlined MS-based assay, CombE-IDMS, which does not rely on antisera/antibodies or reference antigens, as a potential rapidly deployable alternate potency method through a comparison with SRID on adjuvanted seasonal quadrivalent vaccine cell-based (aQIVc) materials. In this report, we further demonstrate that the CombE-IDMS method can also be applied to measure the potency of pre-pandemic H5N1 and H5N8 monovalent vaccine materials, each subtype both unadjuvanted and adjuvanted, through a forced degradation study. Overall, CombE-IDMS results align with those of the gold standard SRID method on both H5N1 and H5N8 materials under conditions of thermal, pH, oxidative and freeze/thaw stress, lending further evidence for the CombE-IDMS method's suitability as an alternate assay for potency of both seasonal and pandemic influenza vaccines. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) can be used to complement immunization for the therapy of influenza virus infection. We have established the pig, a natural large animal host for influenza A, with many physiological, immunological, and anatomical similarities to humans, as an appropriate model for testing mAbs. We have evaluated the protective efficacy of the strongly neutralizing human anti-hemagglutinin mAb, 2-12C in the pig influenza model. Intravenous administration of recombinant 2-12C reduced virus load and lung pathology, however, it did not prevent virus nasal shedding and, consequently, transmission. This may be because the pigs were directly infected intranasally with a high dose of the H1N1pdm09 virus. To address this, we developed a contact challenge model in which the animals were given 2-12C and one day later co-housed with donor pigs previously infected intra-nasally with H1N1pdm09. 2-12C pretreatment completely prevented infection. We also administered a lower dose of 2-12C by aerosol to the respiratory tract, but this did not prevent shedding in the direct challenge model, although it abolished lung infection. We propose that the direct contact challenge model of pig influenza may be useful for evaluating candidate mAbs and emerging delivery platforms prior to clinical trials. [ABSTRACT FROM AUTHOR]

The history of American pharmacy contributions to pandemic responses can be described for five pandemics: 1918 (influenza A/H1N1 virus), 1957–1958 (H2N2 virus), 1968 (H3N2 virus), 2009 (H1N1pdm09 virus), and 2019–2023 (syndrome coronavirus-2 virus). Using historical surveillance data and published literature, this article provides opportunities to reflect on how the pharmacy profession played a role in preparedness and response. [ABSTRACT FROM AUTHOR]

• Vaccination acceptability decreased from 91.1% in 2000 to 61.2% in 2010. • Vaccination acceptability increased during the COVID-19 pandemic. • Higher acceptability among persons with higher incomes and education levels. • Widening social and economic gap in terms of vaccine acceptability over time. This study describes the evolution of vaccination acceptability and associated determinants in the French general population between 2000 and 2021, and vaccinations with the highest vaccine hesitancy between 2010 and 2021. Data were collected from the nine national 'Health Barometer' cross-sectional surveys conducted between 2000 and 2021. These surveys included French-speaking individuals aged 18–75 years old who were selected through randomly generated landline and mobile phone numbers. Participants were asked about their acceptability of vaccination in general and their vaccine hesitancy toward any particular vaccinations. Determinants of vaccination acceptability were studied using univariate and multivariate Poisson regressions. The proportion of persons who found vaccination acceptable in general (i.e., answering "very" or "somewhat" favourable in the survey interview) decreased from 91.1% in 2000 to 61.2% in 2010 (the latter year coinciding with the 2009 H1N1 influenza pandemic), increased in 2014 (78.8%), slightly fluctuated until 2019 (74.2%), and increased again in both 2020 (80.0%) and 2021 (82.5%) during the COVID-19 pandemic. Irrespective of the year, acceptability was higher among persons with higher incomes, those with a higher education level, and individuals not living alone. In 2021, for the first time, vaccination acceptability was higher among persons over 44 years old (versus 18–24 year-olds) and among retired persons (versus workers). The highest hesitancy rate for a vaccine was for the 2009 H1N1 influenza virus in 2010 (41% answering "somewhat" or "very" unfavourable). In 2021, the highest rate was for the COVID-19 vaccine (21%). Unlike the experience of the 2009 AH1N1 influenza pandemic, which led to a collapse in vaccination acceptability among the French general population, acceptability continued to increase during the COVID-19 pandemic. However, the pre-2010 level was not reached. Our results show a tendency towards a widening social and economic gap in terms of vaccine acceptability over time. [ABSTRACT FROM AUTHOR]

Background: Before the COVID-19 pandemic, respiratory pathogens such as influenza, parainfluenza, and respiratory syncytial virus were the most commonly detected viruses among hospitalized patients with respiratory tract infections. Methods: This was a retrospective observational study of inpatients and outpatients who attended Jordan University Hospital and underwent Nasopharyngeal Aspiration (NPA) in the periods from December 2017 to December 2018 and from December 2021 to December 2022. The results of multiplex respiratory pathogen real-time PCR tests for nasopharyngeal swab specimens were extracted from the electronic-based molecular diagnostic laboratory record of JUH. We compared the prevalence of the detected viruses as well as the patients' characteristics and outcomes between the two periods. Results: The total number of included patients was 695. Our analysis showed that a higher percentage of patients with hypertension and diabetes presented before the pandemic compared to the same period after it (p-value < 0.001). The need for O2 devices, white blood cell counts, diastolic blood pressure, and the length of hospital stay were significantly higher among patients who presented before the pandemic (p-value < 0.050). Influenza H1N1 (8.70% vs. 4.03%), influenza B (1.67% vs. 0.25%), parainfluenza (1.00% vs. 0.00%), human metapneumovirus (5.35% vs. 0.76%), adenoviruses (6.35% vs. 3.02%), and coronaviruses (8.70% vs. 3.53%) were detected with higher frequency in the period before the pandemic (p-value = 0.011, 0.045, 0.045, 0.000, 0.035, 0.004). These results were similar in terms of changes in the detection rates of viruses after matching the number of tested patients between the periods before and after the pandemic. Conclusions: We have demonstrated a reduction in the detection of several viruses, which might be due to the increase in public awareness toward infection protection measures after the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Upper respiratory tract infections (URTIs) are caused by a wide range of viruses and bacteria, however, produce similar symptoms. Routine molecular tests are not performed and empirical use of antibiotics in treating URTIs is a major public health concern. In attempt to unveil the diversity of upper respiratory tract pathogens in the community during COVID-19 pandemic, we have screened 153 nasopharyngeal swab samples from patients having flu like symptoms. Materials and methods: We tested nasopharyngeal swabs by real-time multiplex PCR for 19 viruses and 3 bacteria using cartridge based rapid PCR platform. Results: Of 153 patients sample tested, 103 (67.32%) had a laboratory-confirmed respiratory pathogen. Of the 153 swabs tested rhinovirus/enterovirus was found 25(16.34%), influenza 18(11.77%), RSV 13(8.5%), SARS-CoV2-15(11.11%), other coronaviruses 11(7.19%), parainfluenza 16(10.45%), human metapneumovirus 8(5.23%). Out of 18 influenza cases influenza A was 17(11.12%) and influenza B was 1(0.65%). Among 17 influenza A viruses H1N1pdm09 strain was 9(5.88%), H3 was 5(3.27%). These data shows that even in COVID-19 pandemic period rhinovirus/enterovirus and Influenza dominated over all other respiratory viruses and as a causative agent bacteria might play very insignificant role in URTIs. Conclusion: Our data provides strong evidence against empiric antibiotic use for treating URTIs and highlights a strong need for improving the diagnostic capacity for URTIs by using more molecular testing in the country. [ABSTRACT FROM AUTHOR]

Background. Influenza is an acute infectious respiratory disease caused by the influenza virus that seriously damages human health, and the essential way to prevent influenza is the influenza vaccine. Vaccines without adjuvants produce insufficient specific antibodies and therefore require adjuvants to boost antibody titers. Microbes and hosts are a community that needs to ''promote bacteria,'' which could provide new value for the immune effect. Methods. (1) The H1N1 influenza vaccine, in combination with Ginsenoside Rb1, was co-injected into mice intraperitoneally (I.P.). Then, immunoglobulin G and antibody subtype levels were tested by enzyme-linked immunosorbent assay (ELISA). Moreover, mice were infected with a lethal dose of the H1N1 influenza virus (A/Michi- gan/45/2015), and survival status was recorded for 14 days. Lung tissues were stained by hematoxylin and eosin (H&E), and ELISA detected inflammatory factor expression levels. (2) Mice were immunized with Ginsenoside Rb1 combined with quadrivalent influenza inactivated vaccine(IIV4), and then IgG levels were measured by ELISA. (3) Fresh stool was collected for fecal 16S rDNA analysis. Results. Ginsenoside Rb1 boosted IgG and antibody subtypes in the H1N1 influenza vaccine, improved survival of mice after virus challenge, attenuated lung histopathological damage, and reduced inflammatory cytokines expression in IL-6 and TNF-α. The results of 16S rDNA showed that Rb1 decreased species diversity but increased species richness compared to the PBS group and increased the abundance of Akkermansiaceae and Murbaculaceae at the Family and Genus levels compared with the HA+Alum group. Conclusion. Ginsenoside Rb1 has a boosting effect on the immune efficacy of the H1N1 influenza vaccine and is promising as a novel adjuvant to regulate the microecological balance and achieve an anti-infective effect. [ABSTRACT FROM AUTHOR]

Influenza virus infections represent an ongoing public health threat as well as an economic burden. Although seasonal influenza vaccines have been available for some decades, efforts are being made to generate new efficient, flexible, and cost-effective technologies to be transferred into production. Our work describes the development of a model influenza hemagglutinin antigen that is capable of inducing protection against viral challenge in mice. High amounts of the H1 hemagglutinin ectodomain, HA18–528, were expressed in a bacterial system as insoluble inclusion bodies. Solubilization was followed by a thorough differential scanning fluorimetry (DSF)-guided optimization of refolding, which allows for fast and reliable screening of several refolding conditions, yielding tens of milligrams/L of folded protein. Structural and functional analysis revealed native-like folding as well as the presence of a mix of monomers and oligomers in solution. Mice immunized with HA18–528 were protected when exposed to influenza A virus as opposed to mice that received full-length denatured protein. Sera of mice immunized with HA18–528 showed both high titers of antigen-specific IgG1 and IgG2a isotypes as well as viral neutralization activity. These results prove the feasibility of the recombinant bacterial expression system coupled with DSF-guided refolding in providing influenza hemagglutinin for vaccine development. [ABSTRACT FROM AUTHOR]