Search

Background: Influenza infection is highly contagious respiratory illness triggered by the influenza virus, bearing substantial implications for global health. Influenza B viruses, specifically the Victoria and Yamagata lineages, have contributed to the disease burden, and the mismatch between circulating strains and vaccine strains has led to increased mortality and economic costs. Understanding the global epidemiology, seasonal variations, and genetic characteristics of influenza B is crucial for effective prevention and control strategies., Methods: The study investigated influenza B viruses in Shiraz, Iran during the Oct 2017 to Jan 2018. Throat swabs were collected from 235 individuals under 15 with influenza-like symptoms including fever and cough. Samples were stored at -80°C and transported to the lab for further analysis. Viral RNA was extracted and analyzed using Real-time PCR. The hemagglutinin (HA) gene of positive samples was sequenced, and phylogenetic trees were constructed. Amino acids indicative of adaptive mutations were identified using global sequence data., Results: 23 of 235 samples (9.7 %) were positive for influenza B virus. The most common clinical manifestations were rhinorrhea and myalgia, with 20 individuals (87 % of the 23 infected people) each showing these symptoms. The phylogenetic analysis of the HA gene showed that the Victoria isolates were close to the B/Brisbane/60/2008 strain (12.5 % of the positive samples) and belonged to clade-1A, while the Yamagata isolates were close to the B/Phuket/3037/2013 strain (87.5 % of the positive samples) and belonged to clade-3., Conclusion: The study highlights the need for importance vaccine coverage in the Shiraz region to address limited genetic diversity and strain mismatch. Continuous surveillance of mutations in the HA gene resulting in amino acid substitutions and their impact on vaccine efficacy is crucial. This study showed that the circulation of influenza B in Shiraz matched with the recommended Yamagata vaccine strain. These findings contribute to the understanding of influenza B dynamics and emphasize the importance of region-specific prevention and control strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Influenza A and influenza B viruses (FLUAV and FLUBV, respectively) cause significant respiratory disease, hospitalization, and mortality each year. Despite causing at least 25% of the annual disease burden, FLUBV is historically understudied. Unlike FLUAVs, which possess pandemic potential due to their many subtypes and broad host range, FLUBVs are thought to be restricted to only humans and are limited to two lineages. The hemagglutinins (HA) of both influenza types bind glycans terminating in α2,6- or α2,3-sialic acids. For FLUAV, the tropism of human- and avian-origin viruses is well-defined and determined by the terminal sialic acid configuration the HA can accommodate, with avian-origin viruses binding α2,3-linked sialic acids and human-origin viruses binding α2,6-linked sialic acids. In contrast, less is known about FLUBV receptor binding and its impact on host tropism. This review discusses the current literature on FLUBV receptor specificity, HA glycosylation, and their roles in virus tropism, evolution, and infection. While the focus is on findings in the past dozen years, it should be noted that the most current approaches for measuring virus-glycan interactions have not yet been applied to FLUBV and knowledge gaps remain.

Purpose and Method: Necrotizing tracheobronchitis is a rare clinical entity presented as a necrotic inflammation involving the mainstem trachea and distal bronchi. We reported a case of severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus (MRSA) co-infection in an immunocompetent patient., Case Presentation: We described a 36-year-old man with initial symptoms of cough, rigors, muscle soreness and fever. His status rapidly deteriorated two days later and he was intubated. Bronchoscopy demonstrated severe necrotizing tracheobronchitis, and CT imaging demonstrated multiple patchy and cavitation formation in both lungs. Next-generation sequencing (NGS) and bronchoalveolar lavage fluid (BALF) culture supported the co-infection of influenza B and MRSA. We also found T lymphocyte and NK lymphocyte functions were extremely suppressed during illness exacerbation. The patient was treated with antivirals and antibiotics including vancomycin. Subsequent bronchoscopy and CT scans revealed significant improvement of the airway and pulmonary lesions, and the lymphocyte functions were restored. Finally, this patient was discharged successfully., Conclusion: Necrotizing tracheobronchitis should be suspected in patients with rapid deterioration after influenza B infection. The timely diagnosis of co-infection and accurate antibiotics are important to effective treatment., (© 2024. The Author(s).)

Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individual following seasonal vaccination. Competition-binding experiments suggested the antibodies recognized two major antigenic sites. One group, which included mAb FluB-393, broadly inhibited IBV NA sialidase activity, protected prophylactically in vivo, and bound to the lateral corner of NA. The second group contained an active site mAb, FluB-400, that broadly inhibited IBV NA sialidase activity and virus replication in vitro in primary human respiratory epithelial cell cultures and protected against IBV in vivo when administered systemically or intranasally. Overall, the findings described here shape our mechanistic understanding of the human immune response to the IBV NA glycoprotein through the demonstration of two mAb delivery routes for protection against IBV and the identification of potential IBV therapeutic candidates., Competing Interests: Declaration of interests L.E.W. serves as a consultant for BigHat Biosciences. The content of this article is solely the responsibility of the authors and does not represent the official views of BigHat Biosciences. C.B.C. serves as a consultant to GlaxoSmithKline, Sanofi, TDCowen Investments, Guidepoint Global, Debiopharm, and CommenseBio and receives royalties from UpToDate. The laboratory of C.B.C. receives funding for unrelated work from Moderna. J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, GlaxoSmithKline, and BTG International Inc; is a member of the Scientific Advisory Board of Meissa Vaccines; a former member of the Scientific Advisory Board of Gigagen (Grifols); and is founder of IDBiologics. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda, and IDBiologics during the conduct of the study. The opinions, interpretations, conclusions, and recommendations contained herein are those of the authors and are not necessarily endorsed by the US Department of Defense. E.D., T.E.E., and B.J.D. are employees of Integral Molecular, B.J.D. is a shareholder of Integral Molecular. Vanderbilt University has applied for a patent pertinent to some of the materials in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Influenza affects individuals of all ages and poses a significant threat during pandemics, epidemics, and sporadic outbreaks. Neuraminidase inhibitors (NAIs) are currently the first choice in the treatment and prevention of influenza, but their use can be hindered by viral resistance., Areas Covered: This review summarizes current NAIs pharmacological profiles, their current place in therapy, and the mechanisms of viral resistance and outlines possible new indications, ways of administration, and novel candidate NAIs compounds., Expert Opinion: NAIs represent a versatile group of compounds with diverse administration methods and pharmacokinetics. While the prevalence of influenza virus resistance to NAIs remains low, there is heightened vigilance due to the pandemic potential of influenza. Several novel NAIs and derivatives are currently under assessment at various stages of development for the treatment and prevention of influenza.

Benign childhood myositis is a self-limiting inflammatory condition that primarily affects schoolaged boys during the winter months. It is associated with respiratory viral infections, such as influenza A and B viruses, respiratory syncytial virus (RSV), and Mycoplasma pneumoniae, among others. In September 2022, an epidemiological alert was raised due to a high number of reported cases in the metropolitan area of Buenos Aires. We present two cases of female adolescents, aged 10 and 14 years, who developed this condition in association with influenza B virus infection. Their treatment and follow-up differed based on their clinical presentation and laboratory findings. This entity should be considered in the differential diagnosis of lower limb myalgia, difficulty walking, and functional impotence. It is necessary to establish management guidelines according to the clinic and laboratory. The search for respiratory viruses, mainly influenza, should be done taking into account the local epidemiology.

The sentinel hospital-based influenza-like illness (ILI) surveillance network was established in China since the 2009 H1N1 pandemic. This network plays important roles in monitoring influenza virus variation and identifying novel respiratory pathogens. In this study, we characterized the pathogen spectrum pattern (PSP) of ILI based on three sentinel hospitals and analyzed the significant change of PSP during the COVID-19 epidemic. The notable change of influenza virus spectrum was observed since the beginning of COVID-19 outbreak, and we found persistent domination of Victoria lineage of influenza B virus and "extinction" of A/H1N1, A/H3N2, and B/Yamagata during the dynamic Zero-COVID-19 pandemic in Nanchang, China. However, these strains intermittently co-circulated before the COVID-19., Competing Interests: None., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Data on the disease burden and circulation patterns of influenza B virus lineages for Iran are limited., Objective: This review aims to describe the pattern of influenza B occurrence in Iran, comparing it with the proposed vaccine strains and determining the match and mismatch with the prescribed vaccine annually., Methods: Various sources were used to retrieve information of the data; such as information from an online search of databases such as FluNet, GISAID, and NCBI. After extracting protein sequence records in GISAID, sequence alignment with vaccine strain and construction of a phylogenetic tree were performed. Subsequently, categories of the registered circulating strains were evaluated for matching with the vaccine strains., Results: Of the total registered influenza-positive samples, 20.21% were related to influenza B virus. The phylogenic tree was designed based on 43 samples registered in the GISAID database; 76.74 and 23.25% sequences were of Yamagata and Victoria lineages, respectively. The most prevalent influenza B virus strains circulating during the study years belonged to the Yamagata lineage. In general, the match of the influenza B virus predominant circulating strains with administrated vaccines was observed in Iran. However, a high level of mismatch between the vaccine strain and Iranian isolates was identified in 2016‒2017., Conclusion: The review of match and mismatch in influenza vaccine in order to improve the composition of the prescribed vaccine in each region is very important because the vaccine efficacy decreased when the strain included in vaccine did not match the circulating epidemic strain.

Background: The emergence of COVID-19 and the implementation of preventive measures and behavioral changes have led to a significant decrease in the prevalence of other respiratory viruses. However, the manner in which seasonal viruses will reemerge in the absence of COVID-19-related restrictions remains unknown., Methods: Patients presenting with influenza-like illness in two hospitals in Beijing were subjected to testing for COVID-19, influenza A, and influenza B to determine the causative agent for viral infections. The prevalence of influenza B across China was confirmed using data from the Centers for Disease Control, China (China CDC). Clinical characteristics, laboratory findings, imaging results, and mortality data were collected for a cohort of 70 hospitalized patients with confirmed influenza B from 9 hospitals across China., Results: Starting from October 2021, a substantial increase in the number of patients visiting the designated fever clinics in Beijing was observed, with this trend continuing until January 2022. COVID-19 tests conducted on these patients yielded negative results, while the positivity rate for influenza rose from approximately 8% in October 2021 to over 40% by late January 2022. The cases started to decline after this peak. Data from China CDC confirmed that influenza B is a major pathogen during the season. Sequencing of the viral strain revealed the presence of the Victoria-like lineage of the influenza B strain, with minor variations from the Florida/39/2018 strain. Analysis of the hospitalized patients' characteristics indicated that severe cases were relatively more prevalent among younger individuals, with an average age of 40.9 ± 24.1 years. Among the seven patients who succumbed to influenza, the average age was 30 ± 30.1 years. These patients exhibited secondary infections involving either bacterial or fungal pathogens and displayed elevated levels of cell death markers (such as LDH) and coagulation pathway markers (D-dimer)., Conclusion: Influenza B represents a significant infection threat and can lead to substantial morbidity and mortality, particularly among young patients. To mitigate morbidity and mortality rates, it is imperative to implement appropriate vaccination and other preventive strategies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: The effectiveness of oseltamivir versus peramivir in children infected with influenza remains unclear. This study aimed to evaluate their effectiveness in young children (aged 0-5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV)., Methods: We analyzed a cohort of 1662 young children with either IAV (N = 1095) or IBV (N = 567) who received oseltamivir or peramivir treatment from January 1, 2018 to March 31, 2022. Propensity score matching methods were applied to match children who were oseltamivir-treated versus peramivir-treated., Results: Children who were IAV-infected and IBV-infected shared similar features, such as influenza-associated symptoms and comorbidities at baseline. Among children infected with IAV with bacterial coinfection, the recovery rate was significantly greater in children treated with oseltamivir than in children treated with peramivir (15.6% vs 4.4%, P = 0.01). The median duration of hospitalization was also shorter in children treated with oseltamivir. Among children infected with IAV without bacterial coinfection, the recovery rate was greater in children treated with oseltamivir than in children treated with peramivir (21.1% vs 3.7%, P = 0.002). However, oseltamivir and peramivir offered similar recovery rates and duration of hospitalization (P >0.05 for both) among children infected with IBV., Conclusion: Oseltamivir and peramivir exhibit similar effectiveness in young children with severe influenza B, whereas oseltamivir demonstrated improved recovery and shorter hospitalization in the treatment of severe influenza A in hospitalized children., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Influenza causes a significant disease burden as an acute respiratory infection. Evidence suggests that meteorological factors can influence the spread of influenza; however, the association between these factors and influenza activity remains controversial. In this study, we investigated the impact of temperature on influenza across different regions of China based on the meteorological data and influenza data from 554 sentinel hospitals in 30 provinces and municipalities in China from 2010 to 2017. A distributed lag nonlinear model (DLNM) was used to analyze the exposure lag response of daily mean temperatures to the risk of influenza-like illness (ILI), influenza A (Flu A), and influenza B (Flu B). We found that in northern China, low temperatures increased the risk of ILI, Flu A, and Flu B, while in central and southern China, both low and high temperatures increased the risk of ILI and Flu A, and only low temperatures increased the risk of Flu B. This study suggests that temperature is closely associated with the influenza activity in China. Temperature should be integrated into the current public health surveillance system for highly accurate influenza warnings and the timely implementation of disease prevention and control measures., Competing Interests: The authors declare no conflict of interest.

The objective of the study was to identify potential inhibitors of Influenza surface Hemagglutinin (HA), which plays key role in the entry and replication of Influenza virus into the host cell. As ligands, seven vitamins and their derivatives were selected after initial screening based on their metabolizable capacity with no reported side effects, for in silico studies. Docking, and Post docking analysis (X Score and Ligplot+) were performed against nine Influenza HA targets for the vitamins and its derivatives. 'Vitamin Derivatives' with top docking score were further analysed by MD Simulations and free energy was calculated using MMGBSA module. FMNNa and FMNCa displayed high binding free energy with Influenza HA, thereby exhibiting potential as HA inhibitors.Communicated by Ramaswamy H. Sarma.

Background: Apart from age and underlying disease, predictors of adverse outcome in children hospitalized with influenza are poorly understood., Objectives: Our goal is to determine clinical and laboratory predictors that help identify children at increased risk for an unfavorable course and identify differences in clinical presentation between serotypes., Study Design: A retrospective, observational cohort study conducted at the Rambam Healthcare Campus in Haifa. We analyzed data from electronic records of children < 18 years with influenza A or B infection hospitalized between 2009 and 2020. Multivariate regression analyses were used to identify predictors of unfavorable outcome, defined as mortality, ICU admission, intubation, prolonged length of stay, or bacterial coinfection., Results: A total of 1077 children were included, of whom 54% were male. The median age was 2.5 years. Influenza A was detected in 797 (74%) and influenza B in 286 (26%) of the cases. Children with influenza A were younger (OR 2.51, 95%CI 1.90-3.33), more likely to have oxygen desaturation <90% (OR 2.44, 95%CI 1.23-4.83) and an elevated CRP>5 mg/dL on admission (OR 2.67, 95% CI 1.63-4.37). In multivariate analyses, oxygen desaturation <90% and CRP > 5 mg/dL at admission had an 11.1 and 4-fold increased risk of unfavorable outcome, respectively, in addition to a 3.1 and 1.6-fold increased risk in the presence of underlying condition or influenza A serotype infection, respectively., Conclusions: Data available on admission can help identify children hospitalized with influenza who are at increased risk for complications and unfavorable outcome, encouraging aggressive treatment and care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

With the COVID-19 pandemic still ongoing, the annual season of influenza and other respiratory virus epidemics has arrived. Specimens from patients suspected of respiratory viruses infection were collected. Viral detection was performed following RNA extraction and real-time RT-PCR. During the study period, we received and tested a total of 606 specimens. Rhinovirus virus was the viral type most prevalent, detected in 186 (45.47%) specimens. The age range of patients positive for influenza A, influenza A (H1N1), and influenza B was 18 days to 13 years. With female prevalence for this viral type, cough and asthma were the main clinical manifestations presented by this viral type. Our results indicate that rhinoviruses, adenoviruses, metapneumoviruses, and influenza are among the most important agents of ARI in pediatrics. The epidemic period of respiratory infections observed in Goiânia can be useful for planning and implementing some prevention strategies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Influenza virus can cause serious respiratory illness sometimes resulting in epidemics and pandemics associated with significant morbidity and mortality across the globe. Hence, continuous surveillance of the activity of the influenza virus and its subtypes is necessary to help the policy makers to take effective and appropriate decisions regarding its control. The study aimed to determine distribution of influenza viruses in Assam of north-east India having subtropical climate that may lead to viral subtype divergence., Methods: Clinically suspected ninety cases with Influenza like illness (ILI) were included, irrespective of age and sex during the period 1st July 2018 to 30th June 2019. Aseptically collected Nasopharyngeal swabs in viral transport media (VTM) were tested by conventional Reverse Transcriptase Polymerase Chain Reaction (RT PCR) for detection of Influenza A and Influenza B viruses which were further processed for detection of subtypes such as H1N1 pdm09, H3N2 and Influenza B (Yamagata and Victoria lineage). Normally distributed continuous variables were summarised by mean and standard deviation. All categorical variables were summarised as percentages., Results: Influenza activity was seen in 42.2% of ILI cases with male predominance (57.9%). Influenza A was the predominant type (84.2%). Among the subtypes, A(H1N1) pdm09 was predominant (76.3%) followed by Influenza B (Victoria lineages) (15.8%) and AH3N2 (7.9%). Significant difference was observed between different subtypes with regard to age distribution only. Influenza activity in Assam showed two seasonal peaks; the primary one from May to July and the secondary from November to February., Conclusion: The study described the distribution of different Influenza viruses and its subtypes in Assam along with their seasonal activities. These findings will help to formulate the policy for its prevention and control in Assam as well as to monitor the efficacy of the current influenza vaccine., Competing Interests: Conflict of interest None., (Copyright © 2022 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

As new vaccine technologies and platforms, such as nanoparticles and novel adjuvants, are developed to aid in the establishment of a universal influenza vaccine, studying traditional influenza split/subunit vaccines should not be overlooked. Commercially available vaccines are typically studied in terms of influenza A H1 and H3 viruses but influenza B viruses need to be examined as well. Thus, there is a need to both understand the limitations of split/subunit vaccines and develop strategies to overcome those limitations, particularly their ability to elicit cross-reactive antibodies to the co-circulating Victoria (B-V) and Yamagata (B-Y) lineages of human influenza B viruses. In this study, we compared three commercial influenza hemagglutinin (HA) split/subunit vaccines, one quadrivalent (H1, H3, B-V, B-Y HAs) and two trivalent (H1, H3, B-V HAs), to characterize potential differences in their antibody responses and protection against a B-Y challenge. We found that the trivalent adjuvanted vaccine Fluad, formulated without B-Y HA, was able to produce antibodies to B-Y (cross-lineage) on a similar level to those elicited from a quadrivalent vaccine (Flucelvax) containing both B-V and B-Y HAs. Interestingly, Fluad protected mice from a lethal cross-lineage B-Y viral challenge, while another trivalent vaccine, Fluzone HD, failed to elicit antibodies or full protection following challenge. Fluad immunization also diminished viral burden in the lungs compared to Fluzone and saline groups. The success of a trivalent vaccine to provide protection from a cross-lineage influenza B challenge, similar to a quadrivalent vaccine, suggests that further analysis of different split/subunit vaccine formulations could identify mechanisms for vaccines to target antigenically different viruses. Understanding how to increase the breadth of the immune response following immunization will be needed for universal influenza vaccine development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Myers, Gallagher, Woolfork, Stradtmann-Carvalho, Maldonado-Puga, Bock, Boyoglu-Barnum, Syeda, Creanga, Alves, Kanekiyo and Harris.)

Background: Coinfections with respiratory viruses among SARS CoV-2 patients have been reported by several studies during the current COVID-19 pandemic. Most of these studies designated these coinfections as being hospital-acquired infections; however, there is inadequate knowledge about community-acquired respiratory coinfections among SARS CoV-2 patients., Methods: In this retrospective cohort study, we investigated the seroprevalence of influenza A, influenza B, and parainfluenza-2 among newly hospitalized patients with confirmed COVID-19 infections (n = 163). The study was conducted during the early phase of the COVID-19 pandemic in Saudi Arabia (from April to October 2020). The patients' serum samples were subjected to commercial immunoglobulin M (IgM) antibody tests against the three aforementioned viruses., Results: Seropositivity for influenza A and B and parainfluenza-2 occurred only in 4.2% (7/163) of COVID-19 patients, indicating simultaneous acute infections of these three viruses with SARS CoV-2 infection. All coinfection cases were mild and misdiagnosed during the care period in the hospital., Conclusion: This study highlights the low prevalence of community-acquired respiratory infections among COVID-19 patients in the current pandemic and we discussed the possible factors for this finding. During newly emerging epidemics or pandemics, considering other respiratory viruses circulating in the community is essential to avoid their misdiagnosis and account for their possible negative effects on pandemic disease management and prognosis., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests that could have influenced the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this review, we analyze the epidemiological and ecological features of influenza B, one of the most common and severe respiratory infections. The review presents various strategies for cross-protective influenza B vaccine development, including recombinant viruses, virus-like particles, and recombinant proteins. We provide an overview of viral proteins as cross-protective vaccine targets, along with other updated broadly protective vaccine strategies. The importance of developing such vaccines lies not only in influenza B prevention, but also in the very attractive prospect of eradicating the influenza B virus in the human population.

The influenza virus B belongs to the family Orthomyxoviriridae and to the genus Influenzavirus B. It has a negative RNA-type genome made up of about 14,648 nucleotides divided into eight different segments that encode about 11 proteins. Before 1980 all influenza B viruses belonged to a single genetic lineage; but in this year two antigenically and genetically distinct lineages emerged which were named B/Victoria/2/1987 and B/Yamagata/16/1988. Intralineage and interlineage genetic exchange processes have been demonstrated; The most frequent of them are those in which the Victoria lineage acquires genes from the Yamagata lineage. It has been proposed that the differences in the evolutionary dynamics of the two lineages are due to the different binding preferences of influenza hemagglutinin to the cellular receptor. The Victoria lineage has shown the ability to bind to cell receptors with sialic acid residues at the α-2,3 and α-2,6 positions; whereas the Yamagata lineage does so exclusively in the human α-2,6 positions of the respiratory tract. Low circulation in recent months may have contributed to the temporary elimination ("extinction") of the Yamagata lineage. Since 2017, almost all of the strains of this lineage belong to clade 3A, when previously multiple circulating clades were detected. Although this clade 3A is diverse at the genetic level and has acquired surrogate mutations in the hemagglutinin gene, these have not determined significant antigenic changes that have made it necessary to replace its antigenic component (B/Pukhet/3073/2013) in the influenza vaccine since 2015., (©The Author 2022. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Influenza virus types A and B are responsible for acute viral infections that affect annually 1 billion people, with 290,000 to 650,000 deaths worldwide. In this study, we investigated the circulation of influenza B viruses over a 10-year period (2010-2019). Specimens from patients suspected of influenza infection were collected. Influenza detection was performed following RNA extraction and real-time RT-PCR. Genes coding for hemagglutinin (HA) and neuraminidase (NA) of influenza B viruses were partially sequenced, and phylogenetic analyses were carried out subsequently. During the study period, we received and tested a total of 15,156 specimens. Influenza B virus was detected in 1322 (8.7%) specimens. The mean age of influenza B positive patients was 10.9 years. When compared to reference viruses, HA genes from Senegalese circulating viruses showed deletions in the HA1 region. Phylogenetic analysis highlighted the co-circulation of B/Victoria and B/Yamagata lineage viruses with reassortant viruses. We also noted a clear seasonal pattern of circulation of influenza B viruses in Senegal.

A total of 3425 influenza B viruses collected from the Asia-Pacific region were tested against the four registered neuraminidase inhibitors (NAIs) (oseltamivir carboxylate, zanamivir, peramivir and laninamivir) as part of the routine surveillance work at the WHO Collaborating Centre for Research and Reference on Influenza, Melbourne between 2016 and 2020. Forty-five influenza B viruses with reduced susceptibility to one or more NAIs were identified. While the majority of these had neuraminidase (NA) mutations that were known to confer NAIs resistance, fifteen had NA mutations that had not been confirmed as being responsible for reduced NAIs susceptibility. Eleven of these NA mutations of concern were investigated using reverse genetics (RG) techniques to verify that these mutations were the cause of the reduced NAI susceptibility. All mutations were introduced separately into the NA of B/Brisbane/27/2016 (a B Victoria-lineage virus) or B/Yamanashi/166/98 (a B Yamagata-lineage virus) and the effects of these were analysed by an in vitro NAI assay. The T146K substitution in the NA of B Victoria and Yamagata-lineages resulted in a large increase in the IC 50 for peramivir (>1000-fold increase in the mean IC 50 of sensitive viruses with T146) with smaller increases for zanamivir and oseltamivir. A proline substitution (T146P) had a slightly lower (>700-fold) effect on the peramivir IC 50 and also on the other NAIs. The presence of a second NA mutation at N169S combined with the T146P further increased the IC 50 of peramivir (>7000-fold) and the other NAIs. A synergistic effect was also confirmed for dual NA mutations with G247D + I361V which showed a modest increase in the IC 50 for oseltamivir (6-fold). Only one of two RG-viruses with the mutation G108E could be rescued and it had a high IC 50 against zanamivir (>4000-fold) and laninamivir (>7000-fold), but a lower IC 50 against oseltamivir (>200-fold). NA mutations H101L, A200T, D432G, H439P and H439R were also confirmed to somewhat reduce the in vitro susceptibility of influenza B viruses to the NAIs. Overall, this study identifies the potential impact of selected mutations on the clinical performance of NAIs when used to treat influenza B infection in humans., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Background: Influenza B accounts for approximately one fourth of the seasonal influenza burden. However, research on the importance of influenza B has received less attention compared to influenza A. We sought to describe the association of both coinfections and comorbidities with disease severity among adults presenting to emergency departments (ED) with influenza B., Methods: Nasopharyngeal samples from patients found to be influenza B positive in four US and three Taiwanese ED over four consecutive influenza seasons (2014-2018) were tested for coinfections with the ePlex RP RUO panel. Multivariable logistic regressions were fitted to model adjusted odds ratios (aOR) for two severity outcomes separately: hospitalization and pneumonia diagnosis. Adjusting for demographic factors, underlying health conditions, and the National Early Warning Score (NEWS), we estimated the association of upper respiratory coinfections and comorbidity with disease severity (including hospitalization or pneumonia)., Results: Amongst all influenza B positive individuals (n = 446), presence of another upper respiratory pathogen was associated with an increased likelihood of hospitalization (aOR = 2.99 [95% confidence interval (95% CI): 1.14-7.85, p = 0.026]) and pneumonia (aOR = 2.27 [95% CI: 1.25-4.09, p = 0.007]). Chronic lung diseases (CLD) were the strongest predictor for hospitalization (aOR = 3.43 [95% CI: 2.98-3.95, p < 0.001]), but not for pneumonia (aOR = 1.73 [95% CI: 0.80-3.78, p = 0.166])., Conclusion: Amongst ED patients infected with influenza B, the presence of other upper respiratory pathogens was independently associated with both hospitalization and pneumonia; presence of CLD was also associated with hospitalization. These findings may be informative for ED clinician's in managing patients infected with influenza B., (© 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Influenza-like illness (ILI) is one of the most important public health problems globally, causing an enormous disease burden. Influenza infections are the most common cause of ILI. Bacterial and virus co-infection is common yet the data of co-infection with influenza A and B viruses are scarce. To identify the epidemiological patterns of and co-infection of influenza A and B in Anhui province, China, we analyzed the surveillance data of 5 years from 2009 to 2014 collected by the Chinese National influenzas network. The results showed that the weekly ratio of ILI was 3.96 ± 1.9% (95% CI 3.73-4.2%) in outpatients and the highest affected population was children under 5 years old. The epidemic of influenza viruses was highest during 2009-2010. For the other 4 surveillance years, school-aged people (5-14 years) were the most highly affected population. Influenza B and H3N2 viruses were more prevalent than H1N1pdm09 virus after 2010. In addition, a significant co-circulation of influenza A (H1N1pdm09 and H3N2) and influenza B virus was detected with 0.057% PCR positive rate during 2009-2014 in Eastern China, yet isolated only in pediatric patients. Our data reveals school-aged population would be the main vulnerable population and a distinct seasonality for influenza. In addition, the co-infection of influenza A and B were found in Anhui Province, China. Ongoing surveillance is critical to understand the seasonality variation and make evidence-based vaccination recommendations. Information on the epidemiological patterns and co-infections of influenza A and B can help us to implement different strategies for selecting vaccine formulations and monitoring new emerging influenza strains. In addition, the identification of the susceptible population can help us to develop more precise protection measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Hou, Chen, Yu, Chen, He, Liu, Gong, Huang, Wu, Pan and Gao.)

Background: Benign acute childhood myositis (BACM) is associated with several viral infections. The aim of this study was to evaluate the progression of myositis symptoms, laboratory findings and oseltamivir treatment in children with influenza- and non-influenza-associated BACM., Methods: Patients aged 0-18 years old, admitted to the pediatric emergency department in the seasonal influenza period between 2018 and 2020 were retrospectively analyzed. Patients with acute onset calf tenderness, pain, difficulty in walking and elevated serum creatine phosphokinase were included and were grouped according to influenza rapid test kit results as influenza (A and B) positive, and influenza negative. The time to symptom resolution, laboratory data and the oseltamivir treatment were compared between the groups., Results: There were 94 patients (67 male, 27 female) with a mean age of 77 ± 22 months. Influenza A was detected in 21, influenza B in 27, and neither were detected in 46 patients. Time to symptom resolution of BACM was shorter in the influenza-positive patients than in influenza-negative patients (2.9 ± 1.4 days and 3.5 ± 1.5 days, respectively, P = 0.027). Oseltamivir did not reduce the symptom resolution time in influenza patients. All children had normal hemoglobin and platelet counts, elevated creatine phosphokinase and 76% of them had leukopenia. Neither clinical recurrence nor metabolic disease were reported., Conclusion: Symptoms of BACM tended to resolve slightly earlier in influenza-positive patients and the duration of symptoms was not affected by oseltamivir treatment., (© 2022 Japan Pediatric Society.)

Background: Through the comparison of the demographic, epidemiological, and clinical characteristics of hospital human influenza (influenza A (H1N1) pdm09, H3N2, and B)-related and hospitalized avian-origin influenza A (H7N9)-related viral pneumonia patients, find the different between them., Methods: A retrospective study was conducted in hospitalized influenza-related viral pneumonia patients., Results: Human influenza A-related patients in the 35-49-year-old group were more than those with B pneumonia patients (p = 0.027), and relatively less in the ≥ 65-year-old group than B pneumonia patients (p = 0.079). The proportion of comorbid condition to human influenza A pneumonia was 58%, lower than B pneumonia and H7N9 pneumonia patients (78% vs. 77.8%; p = 0.013). The proportion of invasive mechanical ventilation (IMV), lymphocytopenia, elevated lactate dehydrogenase to hospitalized human influenza A-related viral pneumonia patients was higher than B pneumonia patients (p < 0.05), but lower than H7N9 pneumonia patients (p < 0.05). In the multivariate analysis, pulmonary consolidation (odds ratio (OR): 13.67; 95% confidence interval (CI) 1.54-121.12; p = 0.019) and positive bacterial culture (sputum) (OR: 7.71; 95% CI 2.48-24.03; p < 0.001) were independently associated with IMV, while shock (OR: 13.16; 95% CI 2.06-84.07; p = 0.006), white blood cell count > 10,000/mm 3 (OR: 7.22; 95% CI 1.47-35.58; p = 0.015) and positive bacterial culture(blood or sputum) (OR: 6.27; 95% CI 1.36-28.85; p = 0.018) were independently associated with death in the three types hospitalized influenza-related viral pneumonia patients., Conclusions: Hospital influenza B-related viral pneumonia mainly affects the elderly and people with underlying diseases, while human influenza A pneumonia mainly affects the young adults; however, the mortality was similar. The hospitalized human influenza A-related viral pneumonia patients was severer than B pneumonia patients, but milder than H7N9 pneumonia patients. Pulmonary consolidation and positive bacterial culture (sputum) were independently associated with IMV, while shock, white blood cell count > 10,000/mm 3 , and positive bacterial culture (blood or sputum) were independently associated with death to three types hospitalized influenza-related viral pneumonia patients., (© 2021. The Author(s).)

Background: Oseltamivir treatment is currently the only way of managing influenza in young infants for whom influenza vaccines are not licensed, but little data exist on the effectiveness of the treatment in this age group., Methods: In a prospective study, we enrolled 431 newborn infants and followed them up for 10 months during their first respiratory season (September 2017-June 2018). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for determination of the viral etiology. Infants with influenza were re-examined at short intervals, and additional nasopharyngeal specimens were obtained at each visit for measuring the viral load. All infants with symptoms <48 hours received oseltamivir treatment. The parents filled out daily symptom diaries., Results: Among 23 infants with influenza A, the mean total duration of illness in oseltamivir recipients was 82.1 hours, compared with 253.5 hours in infants without treatment (P = .0003). For infants with influenza B, the corresponding durations were 110.0 and 173.9 hours, respectively (P = .03). In infants with influenza A, total symptom scores were significantly lower in oseltamivir-treated infants at all time points between days 3 and 11 after the onset of therapy. In most children with either influenza A or B, viral antigen concentrations declined rapidly within 1-2 days after the initiation of oseltamivir treatment., Conclusions: Oseltamivir treatment of infants with influenza rapidly decreased the viral load in nasopharyngeal secretions and shortened the duration and severity of symptoms. The clinical effectiveness of oseltamivir appeared to be greater against influenza A than against influenza B infections., (© 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Objective: The study aimed to compare the efficacy of antiviral drug alone and antiviral-antibiotic combination therapy in prevention of complications associated with influenza B hospitalized patients., Method: Laboratory confirmed influenza B hospitalized patients presented in emergency room after 48 hours of symptoms onset were identified and divided into two groups; Group-1 patients were initiated on Antiviral drug (oseltamivir) alone while Group-2 patients were initiated on Antiviral drug (oseltamivir) in combination with Antibiotic for at least 3 days. Patients were evaluated for different clinical outcomes among both treatment group., Results: A total of 153 and 131 patients were identified for Group-1 and Group-2, respectively. Clinical outcomes such as secondary bacterial infections (20.9%-vs-9.1%; P = 0.031), need of respiratory support (28.7%-vs-12.9%; P = 0.002), length of hospitalization stay (6.57-vs-4.95 days; P = <0.001), incidences of ICU admission (15.7%-vs-7.6%; P = 0.036), early clinical failure (32.6%-vs-16.1%; P = 0.01), and time to clinical stability (4.83-vs-4.1 days; P = 0.001) were found to be statistically less significant (P-value <0.05) for Group-2 patients., Conclusion: Early initiation of antibiotic therapy in combination with oseltamivir was found to be more efficacious than oseltamivir alone in prevention of influenza B-associated complications especially in high-risk influenza patients.

We performed a neuraminidase sequence analysis of thirty-two pediatric patients with influenza B who visited Teikyo University Hospital from January 2016 to March 2017, and found oseltamivir-resistant samples belonging to the Yamagata and Victoria lineages. Comparison with the neuraminidase sequence of oseltamivir-susceptible B/Brisbane/60/2008 revealed 5 common amino acid substitutions in many of these samples. According to the binding free energy calculation, the N340D and E358K substitutions reduced the affinity of oseltamivir to neuraminidase. Unexpectedly, these substitutions were located distant from the oseltamivir-binding site in neuraminidase. According to the molecular dynamics simulations, the N340D substitution rearranged complicated hydrogen bond networks in an extensive surface region of neuraminidase. The E358K substitution extensively altered the electrostatic potential map of the overall neuraminidase structure. Through these novel mechanisms, the N340D and E358K substitutions indirectly influenced the affinity reduction. These results may be useful for designing drugs for the treatment of oseltamivir-resistant virus infections.Communicated by Ramaswamy H. Sarma.

Neuraminidase inhibitors (NAIs), that currently include oseltamivir (Tamiflu ® ), zanamivir (Relenza ® ), peramivir (Rapivab ® ) and laninamivir (Inavir ® ), constitute an important class of antivirals recommended against seasonal influenza A and B infections. NAIs target the surface NA protein whose sialidase activity is responsible for virion release from infected cells. Because of their pivotal role in the transcription/translation process, the polymerase acidic (PA) and polymerase basic 1 and 2 (PB1 and PB2, respectively) internal proteins also constitute targets of interest for the development of additional anti-influenza agents. Baloxavir marboxil (BXM), an inhibitor of the cap-dependent endonuclease activity of the influenza PA protein, was approved in the United States and Japan in 2018. Baloxavir acid (BXA), the active compound of BXM, demonstrated a potent in vitro activity against different types/subtypes of influenza viruses including seasonal influenza A/B strains as well as avian influenza A viruses with a pandemic potential. A single oral dose of BXM provided virological and clinical benefits that were respectively superior or equal to those displayed by the standard (5 days, twice daily) oseltamivir regimen. Nevertheless, BXM-resistant variants have emerged at relatively high rates in BXM-treated children and adults. Consequently, there is a need to study the fitness (virulence and transmissibility) characteristics of mutants with a high potential to emerge as such variants can compromise the clinical usefulness of BXM. The purpose of this manuscript is to review the fitness properties of influenza A and B isolates harbouring mutations of reduced susceptibility to BXA., (© 2020 John Wiley & Sons Ltd.)

Seasonal Influenza is an acute respiratory illness caused by Influenza A or B viruses. Its presentation is commonly with signs and symptoms of upper respiratory tract involvement such as cough, sore throat and runny nose, associated with generalized systemic symptoms such as fever, headaches, myalgia, and weakness. The severity of symptoms is very variable, ranging from mild self-limiting infection to severe acute respiratory illness requiring intensive interventions. It usually occurs during the winter season and can lead to outbreaks and epidemics worldwide. Influenza is associated with increased morbidity and mortality in high-risk populations including pregnant women and up to two weeks postpartum. Rapid and accurate diagnosis of Influenza is necessary for prompt treatment to reduce morbidity. General public health measures and vaccination are recommended to reduce morbidity and control the spread of the disease. There are many published articles on the several Influenza epidemics that have occurred in this century. In this article, we aim to review the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of seasonal Influenza during pregnancy. We performed an electronic search on PubMed, Cochrane database, National guidelines clearing house and Google Scholar databases., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Influenza is one of the most important viral diseases with high mortality and morbidity that can have a great impact on public health and economy., Objective: To investigate the clinical and epidemiological features of influenza virus A/H1N1, A/H3N2, and B infection in Fars province, southern Iran, in 2015-2019., Methods: In this retrospective cross-sectional study, we assessed the archived data of Syndromic Surveillance System of Iran's Health Ministry, allowed access by Communicable Diseases' Unit of Health chancellor of Shiraz University of Medical Sciences, from December 22, 2015 to September 22, 2019. The participants included all patients whose data were recorded as influenza-like illness (ILI) and severe acute respiratory infections/illness (SARI). Influenza viral infection was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR)., Results: Totally, 1269 patients suspected of influenza were sampled. The mean ± SD of age was 29.40 ± 26.91 years. Fever was the most common symptom (68.6%). The highest incidence was in winter (55.9%). Of 928/1269 laboratory's results which were recorded in the registry, 204 (16.08%) samples were positive and 724 (57.05%) were negative. Among 204 positive results, 191 (15.05%) were influenza type A, and 8 (0.63%) influenza type B. Among patients with definite influenza type A, 34 (2.68%) had H1N1/p subtype, 58 (4.57%) H3N2, and one (0.08%) had other subtypes; however, subtypes were not identified in 7.72% of patients. Six (3.0%) patients with confirmed influenza expired., Conclusion: The incidence of influenza, especially type A, in Fars province, southern Iran is considerable and requires more attention for prevention in health policy programs., (© 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Due to the common symptoms of COVID-19, patients are similar to influenza-like illness. Therefore, the detection method would be crucial to discriminate between SARS-CoV-2 and influenza virus-infected patients. In this study, CRISPR-Cas12a-based detection was applied for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus which would be a practical and attractive application for screening of patients with COVID-19 and influenza in areas with limited resources. The limit of detection for SARS-CoV-2, influenza A, and influenza B detection was 10, 10 3 , and 10 3 copies/reaction, respectively. Moreover, the assays yielded no cross-reactivity against other respiratory viruses. The results revealed that the detection of influenza virus and SARS-CoV-2 by using RT-RPA and CRISPR-Cas12a technology reaches 96.23% sensitivity and 100% specificity for SARS-CoV-2 detection. The sensitivity for influenza virus A and B detections was 85.07% and 94.87%, respectively. In addition, the specificity for influenza virus A and B detections was approximately 96%. In conclusion, the RT-RPA with CRISPR-Cas12a assay was an effective method for the screening of influenza viruses and SARS-CoV-2 which could be applied to detect other infectious diseases in the future.

Baloxavir marboxil (BXM) is an FDA-approved antiviral prodrug for the treatment of influenza A and B infection and postexposure prophylaxis. The active form, baloxavir acid (BXA), targets the cap-snatching endonuclease (PA) of the influenza virus polymerase complex. The nuclease activity delivers the primer for transcription, and previous reports have shown that BXA blocks the nuclease activity with high potency. However, biochemical studies on the mechanism of action are lacking. Structural data have shown that BXA chelates the two divalent metal ions at the active site, like inhibitors of the human immunodeficiency virus type 1 (HIV-1) integrase or ribonuclease (RNase) H. Here we studied the mechanisms underlying the high potency of BXA and how the I38T mutation confers resistance to the drug. Enzyme kinetics with the recombinant heterotrimeric enzyme (FluB-ht) revealed characteristics of a tight binding inhibitor. The apparent inhibitor constant (K i app ) is 12 nM, while the I38T mutation increased K i app by ∼18-fold. Order-of-addition experiments show that a preformed complex of FluB-ht, Mg 2+ ions and BXA is required to observe inhibition, which is consistent with active site binding. Conversely, a preformed complex of FluB-ht and RNA substrate prevents BXA from accessing the active site. Unlike integrase inhibitors that interact with the DNA substrate, BXA behaves like RNase H inhibitors that compete with the nucleic acid at the active site. The collective data support the conclusion that BXA is a tight binding inhibitor and the I38T mutation diminishes these properties., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Influenza B viruses cause significant morbidity and mortality, particularly in children, but the awareness of their impact is often less than influenza A viruses partly due to their lack of pandemic potential. Here, we summarise the biology, epidemiology and disease burden of influenza B, and review existing data on available antivirals for its management. There has long been uncertainty surrounding the clinical efficacy of neuraminidase inhibitors (NAIs) for influenza B treatment. In this article, we bring together the existing data on NAIs and discuss these alongside recent large randomised controlled trial data for the new polymerase inhibitor baloxavir in high-risk influenza B patients. Finally, we offer considerations for the clinical management of influenza B, with a focus on children and high-risk patients where disease burden is highest., (Copyright © 2020. Published by Elsevier B.V.)

Every year, millions of people worldwide are infected with influenza, causing enormous health and economic problems. The most common type of influenza is influenza A. It is known that Natural Killer (NK) cells play an important role in controlling influenza A infection, mostly through the recognition of the viral protein hemagglutinin (HA) by the activating receptor, NKp46. In contrast, little is known regarding NK cell recognition of influenza B viruses, even though they are responsible for a third of all pediatric influenza deaths and are therefore included in the seasonal vaccine each year. Here we show that NKp46 also recognizes influenza B viruses. We show that NKp46 binds the HA protein of influenza B in a sialic acid-dependent manner, and identified the glycosylated residue in NKp46, which is critical for this interaction. We discovered that this interaction has a binding affinity approximately seven times lower than NKp46 binding of influenza A's HA. Finally, we demonstrated, using mice deficient for the mouse orthologue of NKp46, named NCR1, that NKp46 is not important for influenza B elimination. These findings enable us to better understand the interactions between the different influenza viruses and NK cells that are known to be crucial for viral elimination.

Why we only infrequently detect or report two or more respiratory viruses co-infecting an adult host is poorly understood. We report a rare case where influenza B and SARS-CoV-2 caused viral pneumonia in a 74-year-old man diagnosed during the UK winter epidemic/pandemic for these organisms and discuss concepts of co-infection., (© Royal College of Physicians 2020. All rights reserved.)

Despite annual vaccination, influenza B viruses (IBV) cause significant disease with substantial health and socio-economic impacts. Novel vaccination strategies inducing broadly protective and long-lasting immunity across IBV lineages are needed. However, as immune responses toward IBV are largely understudied, host-virus interactions and protective immune mechanisms need to be defined to rationally design such vaccines. Here, we summarize recent advances in our understanding of immunological mechanisms underpinning protection from IBV. We discuss how innate antiviral host factors inhibit IBV replication and the ways by which IBV escapes such restriction. We review the specificity of broadly cross-reactive antibodies and universal T cells, and the mechanisms by which they mediate protection. We highlight important knowledge gaps needing to be addressed to design improved IBV vaccines.

The aim of this study is to evaluate the impact of early (within 2 days after disease onset) neuraminidase inhibitor (NAI) administration on clinical outcomes in patients with laboratory-confirmed influenza B-related pneumonia (FluB-p). This was a multicenter study conducted from 1 January 2013 to 1 May 2019. Data of immunocompetent adult and adolescent FluB-p patients hospitalized at five different teaching hospitals in China were retrospectively collected, including demographic and clinical features as well as clinical and treatment outcomes. Univariate and multivariate logistic regression analyses were performed to assess the effects of early NAI administration on clinical outcomes in FluB-p patients. In total, 386 hospitalized patients with community-onset FluB-p were included in this study, of whom 39.6% (153/386) were treated with NAI early. After adjusting for the weighted propensity scores of treatment, systemic corticosteroid, and antibiotic uses, the results of multivariate logistic regression model indicated that early NAI treatment was associated with the decreased risks of invasive ventilation [odd ratio (OR) 0.325, 95% confidence interval (CI) 0.123-0.858; p = 0.023), admittance to intensive care unit (OR 0.425, 95% CI 0.204-0.882; p = 0.022), and 30-day mortality (OR 0.416, 95% CI 0.184-0.944, p = 0.036)] in FluB-p patients. In addition, the multivariate logistic regression analysis revealed that early NAI treatment (OR 0.306, 95% CI 0.063-0.618; p = 0.010) was an independent predictor for 30-day mortality in patients with FluB-p. Early NAI treatment was associated with better clinical outcomes in FluB-p patients, which supports the recommendations of its use in severe influenza illness.

Objectives: Influenza remains a crucial transmissible disease from community. We aim to identify risk factors associated with mortality among hospitalized patients with severe influenza., Methods: We retrospectively reviewed medical records of adult patients with laboratory-confirmed severe influenza at a medical center between January 2016 and December 2018. The primary outcome was 30-day all-cause mortality., Results: Totally 96 patients were enrolled, with 73 patients in the influenza A group and 23 in the influenza B group. Eighteen (18.8%) deaths occurred within 30 days of hospitalization, including 8 (11%) and 10 (43.5%) of each group. In multivariable Cox regression analysis, factors associated with mortality were underlying diseases of liver cirrhosis (adjusted hazard ratio [AHR], 3.94; 95% CI, 1.07-14.45) and rheumatologic diseases (AHR, 7.45; 95% CI, 2.34-23.69) and the diagnosis of influenza B (AHR, 4.33; 95% CI, 1.68-11.13)., Conclusions: Clinician should early identify high-risk population and warning signs of severe influenza. Our results support the policy of quadrivalent influenza vaccination because influenza B could be associated with high mortality., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Influenza B virus has two distinct lineages (Victoria and Yamagata) and are associated with seasonal influenza epidemics that cause respiratory illness. Influenza B hemagglutinin (HA) is a major surface glycoprotein with the receptor-binding site (RBS) primarily involved in viral pathogenesis. Generally, influenza B exclusively infects the human population which would insinuate that the structural variability of the influenza B HA RBS rarely changes. However, to our knowledge, the potential impact of variations in the influenza B HA RBS structural variability was not fully elucidated. Throughout this study, we generated models from the transitioning (evolving viral lineage) 1998-2018 influenza B/Yamagata HA, verified the quality of each HA model, performed HA RBS structural variability measurements, superimposed varying HA models for comparison, and designed a phylogenetic tree network for further analyses. We found that measurements of the transitioning HA RBS structural variability were generally maintained and, similarly, measurements of the altered (years that differed from the evolving viral lineage, specifically 2003, 2007, 2017) HA RBS structural variability differed from the transitioning HA RBS. Moreover, we observed that the altered HA RBS structural variability favored the formation of a putative Y202-H191 hydrogen bond which we postulate may increase structural stability, thereby, allowing for a winter infection of the virus. Furthermore, we established that changes in HA RBS structural variability does not influence viral evolution, but putatively seasonal infection., Competing Interests: Declaration of competing interest Authors declare no conflict of interest in publishing the proposed manuscript. In particular, authors have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Neurological complications associated with influenza (NCI) are rare events in adults with seasonal influenza. Information about the characteristics of neurological complications and the burden of disease has been limited to case reports, mainly during the pandemic 2009. Influenza-associated encephalopathy/encephalitis (IAE) is one of the most severe and frequently reported NCI, mostly caused by influenza A. Isolated case reports exist about NCI caused by influenza B., Objectives: The aim of this single center retrospective study is the better understanding of the frequency and the characteristics of NCI in adults in season 2017-2018, depending on the influenza subtype A or B., Study Design: We reviewed 874 adult patients with laboratory confirmed influenza admitted to the Christian Doppler University Hospital Salzburg, Austria from December 2017 until March 2018 looking for NCI., Results: 37 (4 %) of the 874 patients with confirmed influenza had NCI. 4 (11 %) had influenza A and 33 (89 %) had influenza B. IAE was the most frequent complication diagnosed in 24 (65 %) patients, of whom all but one had influenza B and 3 (13 %) had neurological residuals. Moreover 6 (16 %) had isolated epileptic seizures, 2 (5 %) had acute inflammatory demyelinating polyneuropathy (AIDP), and 5 (14 %) were classified as having infection-associated stroke., Conclusions: We report an incidence of 4 % for NCI and a high frequency of IAE caused by subtype B. Therefore, we recommend considering both influenza A and B as an etiologic factor of encephalopathy and other neurological disease in adults., Competing Interests: Declaration of Competing Interest Andrea Harrer, Georg Pilz and Patrick Stalzer authors declare that there is no conflict of interest. Eirini Mylonaki received funding for travel expenses and admission fees from Novartis. Ferdinand Otto received travel support from Novartis, Biogen, Merck Serono, Bayer, Teva, and Genzyme. Eugen Trinka reports personal fees from Eisai, personal fees from Everpharma, grants and personal fees from Biogen Idec, personal fees from Medtronics, personal fees from Bial, personal fees from Newbridge, grants and personal fees from UCB Pharma and Eisai, personal fees from GL Pharma, personal fees from GlaxoSmithKline, personal fees from Boehringer, personal fees from Viropharma, from Actavis, grants from Red Bull, grants from Merck, grants from European Union, grants from FWF Österreichischer Fond zur Wissenschaftsförderung, grants from Bundesministerium für Wissenschaft und Forschung, and grants from the Jubiläumsfond der Österreichischen Nationalbank, outside the submitted work. Peter Wipfler received a speaker’s honoraria/research funding/travel support from Novartis, Biogen, Merck Serono, Bayer, Teva, and Genzyme., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Recent influenza B/Victoria lineage viruses contain amino acid deletions at positions 162 to 164 of the haemagglutinin (HA) protein. These amino acid deletions have affected the detection of B/Victoria lineage viruses by the lineage-specific conventional reverse-transcription polymerase chain reaction (RT-PCR) that was recommended by World Health Organization (WHO)., Objectives: We aimed to develop and evaluate a novel lineage-specific RT-PCR for rapid differentiation of the contemporary B/Victoria lineage from B/Yamagata lineage viruses., Study Design: Primers of our in-house RT-PCR were designed to avoid amino acid positions 162 to 164 and to target conserved regions of the HA gene that are specific for B/Victoria and B/Yamagata lineage viruses. Our in-house RT-PCR and WHO RT-PCR were evaluated using influenza B positive clinical specimens or virus culture isolates. Influenza B virus lineage was confirmed by Sanger sequencing., Results: A total of 105 clinical specimens or virus culture isolates were retrieved, including 83 with B/Victoria lineage and 22 with B/Yamagata lineage viruses. Our in-house RT-PCR correctly identified B/Victoria lineage viruses in all 83 samples, including 82 samples with double or triple amino acid deletion in the HA protein. Conversely, the WHO lineage-specific conventional RT-PCR failed to detect any of the 82 samples with HA amino acid deletions. For the 22 samples with B/Yamagata lineage viruses, both RT-PCR assays have correctly identified B/Yamagata lineage in all samples., Conclusions: Our novel lineage-specific RT-PCR has successfully detected all contemporary B/Victoria lineage viruses with amino acid deletions in HA. This protocol is especially useful for laboratories without the equipment for real-time PCR., (© 2019 Wiley Periodicals, Inc.)

Background: There is limited knowledge regarding the risk factors for influenza B virus-associated pneumonia in adults. This study aimed to determine the risk factors for influenza B virus-associated pneumonia in adults., Methods: We used viral surveillance data during the pandemic season between November 2017 and April 2018 from the University of Hong Kong-Shenzhen Hospital medical record database. The files of patients ages 18 years or older were reviewed for demographics, clinical characteristics, laboratory findings, and outcome. Multivariate logistic regression analysis was performed to identify risk factors associated with influenza B virus-associated pneumonia., Results: A total of 78 patients with influenza B, ages 20 to 87 years, were identified. Comparing cases with pneumonia vs cases without pneumonia, there were significant differences in the following: age in years (67.41 ± 16.63 vs 58.16 ± 17.65; P = .028), age group (74.1% vs 51.0%; P = .049), chronic respiratory diseases (70.4% vs 21.6%; P = .000), shortness of breath (40.7% vs13.7%; P = .007), abnormal breath sounds on auscultation (51.9% vs 21.6%; P = .006), and serum alanine transaminase level (30.07 ± 10.73 vs 38.64 ± 21.68; P = .022). Logistic regression models indicated that chronic respiratory diseases (odds ratio, 8.452; 95% confidence interval, 2.768-25.808; P = .000) and shortness of breath (odds ratio, 1.261; 95% confidence interval, 1.015-1.566; P = .036) were independent risk factors., Conclusions: This study suggests that chronic respiratory diseases and shortness of breath are independent risk factors for influenza B virus-associated pneumonia in adult patients., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

We conducted a retrospective cohort study to assess the effect of influenza virus type and subtype on disease severity among hospitalized influenza patients in Spain. We analyzed the cases of 8,985 laboratory-confirmed case-patients hospitalized for severe influenza by using data from a national surveillance system for the period 2010-2017. Hospitalized patients with influenza A(H1N1)pdm09 virus were significantly younger, more frequently had class III obesity, and had a higher risk for pneumonia or acute respiratory distress syndrome than patients infected with influenza A(H3N2) or B (p<0.05). Hospitalized patients with influenza A(H1N1)pdm09 also had a higher risk for intensive care unit admission, death, or both than patients with influenza A(H3N2) or B, independent of other factors. Determining the patterns of influenza-associated severity and how they might differ by virus type and subtype can help guide planning and implementation of adequate control and preventive measures during influenza epidemics.

Background: Understanding the global spatiotemporal pattern of seasonal influenza is essential for influenza control and prevention. Available data on the updated global spatiotemporal pattern of seasonal influenza are scarce. This study aimed to assess the spatiotemporal pattern of seasonal influenza after the 2009 influenza pandemic., Methods: Weekly influenza surveillance data in 86 countries from 2010 to 2017 were obtained from FluNet. First, the proportion of influenza A in total influenza viruses (P A ) was calculated. Second, weekly numbers of influenza positive virus (A and B) were divided by the total number of samples processed to get weekly positive rates of influenza A (RW A ) and influenza B (RW B ). Third, the average positive rates of influenza A (R A ) and influenza B (R B ) for each country were calculated by averaging RW A , and RW B of 52 weeks. A Kruskal-Wallis test was conducted to examine if the year-to-year change in P A in all countries were significant, and a universal kriging method with linear semivariogram model was used to extrapolate R A and R B in all countries., Results: P A ranged from 0.43 in Zambia to 0.98 in Belarus, and P A in countries with higher income was greater than those countries with lower income. The spatial patterns of high R B were the highest in sub-Saharan Africa, Asia-Pacific region and South America. RW A peaked in early weeks in temperate countries, and the peak of RW B occurred a bit later. There were some temperate countries with non-distinct influenza seasonality (e.g., Mauritius and Maldives) and some tropical/subtropical countries with distinct influenza seasonality (e.g., Chile and South Africa)., Conclusions: Influenza seasonality is not predictable in some temperate countries, and it is distinct in Chile, Argentina and South Africa, implying that the optimal timing for influenza vaccination needs to be chosen with caution in these unpredictable countries.

Objectives: The quadrivalent influenza vaccine (QIV) contains two influenza B antigens (one of each B lineage), while the trivalent vaccine (TIV) contains solely one. As a result, a mismatch between the circulating B lineage and the lineage in the TIV occurs frequently. We aimed to compare the frequency of clinically significant outcomes in a large cohort of vaccinees receiving either TIV or QIV., Methods: Historical cohort study of all inactivated influenza vaccinees (aged 3 years and older) in a Health Maintenance Organization insuring 1.2 million individuals, over two influenza seasons in which both vaccines were provided non-selectively. Primary outcome was hospital admissions during the influenza season. Multivariate analysis was performed using logistic regression to adjust for relevant covariates., Results: Our cohort included 150 518 and 168 296 vaccinees in the first (S1) and second season (S2), respectively. The two influenza seasons were characterized by high Influenza B activity. Of those vaccinated with QIV, 2074 of 49 726 (4.2%) and 6563 of 121 741 (5.4%) were hospitalized compared with 7378 of 100 792 (7.3%) and 3372 of 46 555 (7.2%) of those vaccinated with TIV (S1 and S2, respectively). After multivariate analysis adjusting for several covariates (gender, age, socioeconomic status, chronic morbidity, timing of vaccination), compared with TIV recipients, QIV vaccinees had lower odds for hospitalization (OR = 0.92, 95% CI 0.87-0.98 and OR = 0.89, 95% CI 0.85-0.93) or emergency department visit (OR = 0.91, 95% CI 0.87-0.95 and OR = 0.84, 95% CI 0.81-0.87) in S1 and S2, respectively (p < 0.001). Lower odds of mortality and influenza-like illness were also observed in S2 (OR = 0.61, 95% CI 0.50-0.75 and OR = 0.92, 95% CI 0.90-0.95, respectively)., Conclusions: In seasons with relatively high influenza B activity, QIV appeared more protective than TIV in Israel., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)