Risk factors for infection with influenza A(H3N2) virus on a US university campus, October-November 2021.

BACKGROUND: Knowledge of the specific dynamics of influenza introduction and spread in university settings is limited. METHODS: Persons with acute respiratory illness symptoms received influenza testing by molecular assay during October 6-November 23, 2022. Viral sequencing and phylogenetic analysis were conducted on nasal swab samples from case-patients. Case-control analysis of a voluntary survey of persons tested was used to identify factors associated with influenza; logistic regression was conducted to calculate odds ratios and 95% CIs. A subset of case-patients tested during the first month of the outbreak was interviewed to identify sources of introduction and early spread. RESULTS: Among 3268 persons tested, 788 (24.1%) tested positive for influenza; 744 (22.8%) were included in the survey analysis. All 380 sequenced specimens were influenza A (H3N2) virus clade 3C.2a1b.2a.2, suggesting rapid transmission. Influenza (OR [95% CI]) was associated with indoor congregate dining (1.43 [1.002-2.03]), attending large gatherings indoors (1.83 [1.26-2.66]) or outdoors (2.33 [1.64-3.31]), and varied by residence type (apartment with ≥1 roommate: 2.93 [1.21-7.11], residence hall room alone: 4.18 [1.31-13.31], or with roommate: 6.09 [2.46-15.06], or fraternity/sorority house: 15.13 [4.30-53.21], all compared with single-dwelling apartment). Odds of influenza were lower among persons who left campus for ≥1 day during the week before their influenza test (0.49 [0.32-0.75]). Almost all early cases reported attending large events. CONCLUSIONS: Congregate living and activity settings on university campuses can lead to rapid spread of influenza following introduction. Isolating following a positive influenza test or administering antiviral medications to exposed persons may help mitigate outbreaks.

Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells.

Many viruses require proteolytic activation of their envelope proteins for infectivity, and relevant host proteases provide promising drug targets. The transmembrane serine protease 2 (TMPRSS2) has been identified as a major activating protease of influenza A virus (IAV) and various coronaviruses (CoV). Increased TMPRSS2 expression has been associated with a higher risk of severe influenza infection and enhanced susceptibility to SARS-CoV-2. Here, we found that Legionella pneumophila stimulates the increased expression of TMPRSS2-mRNA in Calu-3 human airway cells. We identified flagellin as the dominant structural component inducing TMPRSS2 expression. The flagellin-induced increase was not observed at this magnitude for other virus-activating host proteases. TMPRSS2-mRNA expression was also significantly increased by LPS, Pam3Cys, and Streptococcus pneumoniae, although less pronounced. Multicycle replication of H1N1pdm and H3N2 IAV but not SARS-CoV-2 and SARS-CoV was enhanced by flagellin treatment. Our data suggest that bacteria, particularly flagellated bacteria, up-regulate the expression of TMPRSS2 in human airway cells and, thereby, may support enhanced activation and replication of IAV upon co-infections. In addition, our data indicate a physiological role of TMPRSS2 in antimicrobial host response.

Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine.

Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.

Household Transmission of Influenza A Viruses in 2021-2022.

Importance: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. Objective: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. Design, Setting, and Participants: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. Exposures: Household contacts living with a primary case. Main Outcomes and Measures: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. Results: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. Conclusions and Relevance: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.

The epidemiological pattern of seasonal influenza in four sentinel sites in Iraq.

Introduction: Influenza is an acute viral infection with significant morbidity and mortality. It occurs annually each winter, which is called seasonal influenza, and is preventable through safe vaccine. Aim: The aim of this work is to know the epidemiological pattern of patients with seasonal influenza in Iraqi sentinel sites. Methods: A cross-sectional study was carried out on records of patients who attended four sentinel sites and registered to have influenza-like illness (ILI) or severe acute respiratory infection (SARI), and laboratory investigated. Results: The total number of cases was 1124; 36.2% of them aged 19-39 years; 53.9% were female; 74.9% lived in urban areas; 64.3% diagnosed as ILI; and 35.7% as SARI; 15.9% had diabetes, 12.7% had heart disease, 4.8% had asthma, 3% had a chronic lung disease, and 2% had hematological disease; 94.6% did not get influenza vaccine. About COVID-19 vaccine, 69.4% were not vaccinated, 3.5% got only one dose, and 27.1% completed two doses. Only the SARI cases needed admission; among them, 95.7% were cured. 6.5% were diagnosed with influenza-A virus, 26.1% had COVID-19, and 67.5% were negative. Among those with influenza, 97.3% had H3N2 subtype and 2.7% had H1N1 pdm09. Conclusions: The percentage of influenza virus in Iraq is relatively small. The age, classification of case (ILI or SARI), having diabetes, heart disease, or immunological disease, and taking COVID-19 vaccine have a significant association with influenza. Recommendations: It is needed for similar sentinel sites in other health directorates and for rising health education about seasonal influenza and its vaccine.

The epidemiological features of respiratory tract infection using the multiplex panels detection during COVID-19 pandemic in Shandong province, China.

Respiratory tract infection is one of the most common reasons for both morbidity and mortality worldwide. High attention has been paid to the etiological tracing of respiratory tract infection since the advent of COVID-19. In this study, we aimed to evaluate the epidemiological features of pathogens in respiratory tract infection, especially during COVID-19 pandemic. A total of 7668 patients with respiratory tract infection who admitted to Qilu Hospital of Shandong University from March 2019 to Dec 2021 were retrospectively included. The respiratory tract specimens were detected using a commercial multiplex PCR-based panel assay for common respiratory pathogens including influenza A virus (Flu-A), influenza A virus H1N1 (H1N1), influenza A virus H3N2 (H3N2), influenza B virus (Flu-B), parainfluenza virus (PIV), respiratory syncytial virus (RSV), adenovirus (ADV), Boca virus (Boca), human Rhinovirus (HRV), Metapneumovirus (MPV), Coronavirus (COV), Mycoplasma pneumoniae (MP), and Chlamydia (Ch). The positive rates were compared using a chi-square test. Compared with 2019, the positive rate of pathogen detection during from January 2020 to December 2021 was significantly lower, especially the detection of Flu-A. The positive rate of respiratory pathogen strains was 40.18% during COVID-19 pandemic, and a total of 297 cases (4.69%) of mixed infection with two or more pathogens were detected. There was no statistical difference in the positive rate between male and female patients. However, the positive rates of infection were different among different age groups, with higher incidence of RSV in infancy and toddler group, and MP infection in children and teenager group. While, HRV was the most common pathogen in the adult patients. Moreover, Flu-A and Flu-B were higher in winter, and MP and RSV were higher in spring, autumn and winter. The pathogens such as ADV, BOCA, PIV, and COV were detected without significant seasonal distribution. In conclusion, respiratory pathogen infection rates may vary by age and season, regardless of gender. During the COVID-19 epidemic, blocking transmission routes could help reduce the incidence of respiratory tract infection. The current prevalence of respiratory tract infection pathogens is of great significance for clinical prevention, diagnosis and treatment.

Influenza Vaccine Effectiveness Against Influenza A(H3N2)-Related Illness in the United States During the 2021-2022 Influenza Season.

BACKGROUND: In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. METHODS: Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status. RESULTS: Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2-positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%-49%) overall. CONCLUSIONS: Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.

A Bayesian approach to incorporate structural data into the mapping of genotype to antigenic phenotype of influenza A(H3N2) viruses.

Surface antigens of pathogens are commonly targeted by vaccine-elicited antibodies but antigenic variability, notably in RNA viruses such as influenza, HIV and SARS-CoV-2, pose challenges for control by vaccination. For example, influenza A(H3N2) entered the human population in 1968 causing a pandemic and has since been monitored, along with other seasonal influenza viruses, for the emergence of antigenic drift variants through intensive global surveillance and laboratory characterisation. Statistical models of the relationship between genetic differences among viruses and their antigenic similarity provide useful information to inform vaccine development, though accurate identification of causative mutations is complicated by highly correlated genetic signals that arise due to the evolutionary process. Here, using a sparse hierarchical Bayesian analogue of an experimentally validated model for integrating genetic and antigenic data, we identify the genetic changes in influenza A(H3N2) virus that underpin antigenic drift. We show that incorporating protein structural data into variable selection helps resolve ambiguities arising due to correlated signals, with the proportion of variables representing haemagglutinin positions decisively included, or excluded, increased from 59.8% to 72.4%. The accuracy of variable selection judged by proximity to experimentally determined antigenic sites was improved simultaneously. Structure-guided variable selection thus improves confidence in the identification of genetic explanations of antigenic variation and we also show that prioritising the identification of causative mutations is not detrimental to the predictive capability of the analysis. Indeed, incorporating structural information into variable selection resulted in a model that could more accurately predict antigenic assay titres for phenotypically-uncharacterised virus from genetic sequence. Combined, these analyses have the potential to inform choices of reference viruses, the targeting of laboratory assays, and predictions of the evolutionary success of different genotypes, and can therefore be used to inform vaccine selection processes.

Low prevalence of influenza viruses and predominance of A(H3N2) virus with respect to SARS-CoV-2 during the 2021-2022 season in Bulgaria.

Social distancing, mask-wearing, and travel restrictions during the COVID-19 pandemic have significantly impacted the spread of influenza viruses. The objectives of this study were to analyze the pattern of influenza virus circulation with respect to that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Bulgaria during the 2021-2022 season and to perform a phylogenetic/molecular analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of representative influenza strains. Influenza infection was confirmed using real-time reverse transcription polymerase chain reaction in 93 (4.2%) of the 2193 patients with acute respiratory illness tested wherein all detected viruses were subtyped as A(H3N2). SARS-CoV-2 was identified in 377 (24.3%) of the 1552 patients tested. Significant differences in the incidence of influenza viruses and SARS-CoV-2 were found between individual age groups, outpatients/inpatients, and in the seasonal distribution of cases. Two cases of coinfections were identified. In hospitalized patients, the Ct values of influenza viruses at admission were lower in adults aged ≥65 years (indicating higher viral load) than in children aged 0-14 years (p < 0.05). In SARS-CoV-2-positive inpatients, this association was not statistically significant. HA genes of all A(H3N2) viruses analyzed belonged to subclade 3C.2a1b.2a. The sequenced viruses carried 11 substitutions in HA and 5 in NA, in comparison to the vaccine virus A/Cambodia/e0826360/2020, including several substitutions in the HA antigenic sites B and C. This study revealed extensive changes in the typical epidemiology of influenza infection, including a dramatic reduction in the number of cases, diminished genetic diversity of circulating viruses, changes in age, and seasonal distribution of cases.

Influenza prevalence and vaccine efficacy among diabetic patients in Qatar.

Seasonal influenza viruses may lead to severe illness and mortality in patients with comorbidities, including Diabetes Mellitus (DM). Vaccination against influenza in DM patients may reduce influenza incidence and severity. Before the emergence of the COVID-19 pandemic, influenza infections were the most prevalent respiratory infections in Qatar. Still, reports about influenza prevalence and vaccine efficacy in DM patients have not been reported. This study aimed to analyze influenza prevalence among other respiratory infections and assess influenza vaccine efficacy in DM patients in Qatar. Statistical analysis was performed on data obtained from Hamad Medical Corporation (HMC) database for patients that visited the emergency department (ED) with respiratory-like illnesses. The analysis was done for the period between January 2016 to December 2018. Among 17,525 patients who visited HMC-ED with clinical symptoms of respiratory infections, 2611(14.9%) were reported to have DM. Among DM patients, influenza was the most prevalent respiratory pathogen at 48.9%. Influenza virus A (IVA) was the most circulating type, contributing to 38.4%, followed by IVB contributing to 10.4% of total respiratory infections. Among the typed IVA-positive cases, 33.4% were H1N1, and 7.7% were H3N2. A significant decrease in influenza infections was reported in vaccinated DM patients (14.5%) when compared to non-vaccinated patients (18.9%) (p-value = 0.006). However, there was no significant relaxation in the clinical symptoms among vaccinated DM patients compared to their non-vaccinated counterparts. In conclusion, influenza was the most common etiology for respiratory viral infection among diabetic patients at the leading healthcare provider in Qatar. Although vaccination reduced the incidence rate among DM patients, it was less effective in preventing symptoms. Further studies on a larger cohort and for a more extended period are required to investigate influenza prevalence and vaccine efficacy among DM patients.

A comprehensive analysis of gene expression profiling data in COVID-19 patients for discovery of specific and differential blood biomarker signatures.

COVID-19 is a newly recognized illness with a predominantly respiratory presentation. Although initial analyses have identified groups of candidate gene biomarkers for the diagnosis of COVID-19, they have yet to identify clinically applicable biomarkers, so we need disease-specific diagnostic biomarkers in biofluid and differential diagnosis in comparison with other infectious diseases. This can further increase knowledge of pathogenesis and help guide treatment. Eight transcriptomic profiles of COVID-19 infected versus control samples from peripheral blood (PB), lung tissue, nasopharyngeal swab and bronchoalveolar lavage fluid (BALF) were considered. In order to find COVID-19 potential Specific Blood Differentially expressed genes (SpeBDs), we implemented a strategy based on finding shared pathways of peripheral blood and the most involved tissues in COVID-19 patients. This step was performed to filter blood DEGs with a role in the shared pathways. Furthermore, nine datasets of the three types of Influenza (H1N1, H3N2, and B) were used for the second step. Potential Differential Blood DEGs of COVID-19 versus Influenza (DifBDs) were found by extracting DEGs involved in only enriched pathways by SpeBDs and not by Influenza DEGs. Then in the third step, a machine learning method (a wrapper feature selection approach supervised by four classifiers of k-NN, Random Forest, SVM, Naïve Bayes) was utilized to narrow down the number of SpeBDs and DifBDs and find the most predictive combination of them to select COVID-19 potential Specific Blood Biomarker Signatures (SpeBBSs) and COVID-19 versus influenza Differential Blood Biomarker Signatures (DifBBSs), respectively. After that, models based on SpeBBSs and DifBBSs and the corresponding algorithms were built to assess their performance on an external dataset. Among all the extracted DEGs from the PB dataset (from common PB pathways with BALF, Lung and Swab), 108 unique SpeBD were obtained. Feature selection using Random Forest outperformed its counterparts and selected IGKC, IGLV3-16 and SRP9 among SpeBDs as SpeBBSs. Validation of the constructed model based on these genes and Random Forest on an external dataset resulted in 93.09% Accuracy. Eighty-three pathways enriched by SpeBDs and not by any of the influenza strains were identified, including 87 DifBDs. Using feature selection by Naive Bayes classifier on DifBDs, FMNL2, IGHV3-23, IGLV2-11 and RPL31 were selected as the most predictable DifBBSs. The constructed model based on these genes and Naive Bayes on an external dataset was validated with 87.2% accuracy. Our study identified several candidate blood biomarkers for a potential specific and differential diagnosis of COVID-19. The proposed biomarkers could be valuable targets for practical investigations to validate their potential.

Label-free detection and discrimination of respiratory pathogens based on electrochemical synthesis of biomaterials-mediated plasmonic composites and machine learning analysis.

Seasonal outbreaks of respiratory viral infections remain a global concern, with increasing morbidity and mortality rates recorded annually. Timely and false responses contribute to the widespread of respiratory pathogenic diseases owing to similar symptoms at an early stage and subclinical infection. The prevention of emerging novel viruses and variants is also a big challenge. Reliable point-of-care diagnostic assays for early infection diagnosis play a critical role in the response to threats of epidemics or pandemics. We developed a facile method for specifically identifying different viruses based on surface-enhanced Raman spectroscopy (SERS) with pathogen-mediated composite materials on Au nanodimple electrodes and machine learning (ML) analyses. Virus particles were trapped in three-dimensional plasmonic concave spaces of the electrode via electrokinetic preconcentration, and Au films were simultaneously electrodeposited, leading to the acquisition of intense and in-situ SERS signals from the Au-virus composites for ultrasensitive SERS detection. The method was useful for rapid detection analysis (<15 min), and the ML analysis for specific identification of eight virus species, including human influenza A viruses (i.e., H1N1 and H3N2 strains), human rhinovirus, and human coronavirus, was conducted. The highly accurate classification was achieved using the principal component analysis-support vector machine (98.9%) and convolutional neural network (93.5%) models. This ML-associated SERS technique demonstrated high feasibility for direct multiplex detection of different virus species for on-site applications.

Effectiveness of influenza vaccination in preventing influenza in primary care, Navarre, Spain, 2021/22.

Compared with individuals unvaccinated in the current and three previous influenza seasons, in 2021/22, influenza vaccine effectiveness at primary care level was 37% (95% CI: 16 to 52) for current season vaccination, regardless of previous doses, and 35% (95% CI: -3 to 45) for only previous seasons vaccination. Against influenza A(H3N2), estimates were 39% (95% CI: 16 to 55) and 24% (95% CI: -8 to 47) suggesting moderate effectiveness of current season vaccination and possible remaining effect of prior vaccinations.

Emerging triple-reassortant influenza C virus with household-associated infection during an influenza A(H3N2) outbreak, China, 2022.

Recent research have shown that influenza C virus (ICV) has a possible higher clinical impact than previously thought. But knowledge about ICV is limited compared with influenza A and B viruses, due to poor systematic surveillance and inability to propagate. Herein, a case infected with triple reassortant ICV was identified during an influenza A(H3N2) outbreak, which was the first report of ICV infection in mainland China. Phylogenetic analysis showed that this ICV was triple reassortant. Serological evidence revealed that the index case might be related to family-clustering infection. Therefore, it is essential to heighten surveillance for the prevalence and variation of ICV in China, during the COVID-19 pandemic.

Reduced immunogenicity of BNT162b2 booster vaccination in combination with a tetravalent influenza vaccination: results of a prospective cohort study in 838 health workers.

OBJECTIVE: To investigate the immunogenicity and safety of BNT162b2 booster vaccination with and without a tetravalent influenza vaccine. METHODS: A prospective, open-label cohort study on immunogenicity and safety of COVID-19 booster vaccination with or without a tetravalent influenza vaccine was performed. Eight hundred thirty-eight health care workers were included in the following study arms: BNT162b2 booster-only, influenza-vaccine-only or combination of both. Levels of antibodies against SARS-CoV-2 spike receptor binding domain, and haemagglutinin inhibition tested for four different influenza strains (A(H1N1)pdm09, A(H3N2), B/Victoria, B/Yamagata) were measured at the time of vaccination and 4 weeks later. RESULTS: After 4 weeks, median (interquartile range) levels of antibodies against the receptor binding domain of the viral spike (S) protein and relative change from baseline were high in individuals who received BNTb162b2 booster vaccination only (absolute: 16 600 [10 980-24 360] vs. 12 630 [8198-18 750] BAU/mL [p < 0.0001]; relative increase: 49% [23.6-95.3] vs. 40% [21.9-80.6] [p 0.048]; booster-only n = 521 vs. combination-arm n = 229 respectively). Results were confirmed after matching for sex, age, body mass index, baseline antibody levels and vaccine compound received for primary immunization (absolute: 13 930 [10 610-22 760] vs. 12 520 [8710-17 940]; [p 0.031]; relative increase: 55.7% [27.8-98.5] vs. 42.2% [22.9-74.5]; p 0.045). Adverse events were almost identical in the booster-only and the combination-arm, but numerically low in the influenza arm (525/536 [97.9%] vs. 235/240 [97.9%] vs. 26/33 [78.8 %]). DISCUSSION: Although no safety concerns occurred, our study provides evidence on reduced immunogenicity of a BNT162b2 booster vaccination in combination with a tetravalent influenza vaccine. Further studies investigating new influenza variants as well as potential differences vaccine effectiveness are needed.

High Clinical Burden of Influenza Disease in Adults Aged ≥ 65 Years: Can We Do Better? A Systematic Literature Review.

INTRODUCTION: Influenza is a respiratory infection associated with a significant clinical burden globally. Adults aged ≥ 65 years are at increased risk of severe influenza-related symptoms and complications due to chronic comorbidity and immunosenescence. Annual influenza vaccination is recommended; however, current influenza vaccines confer suboptimal protection, in part due to antigen mismatch and poor durability. This systematic literature review characterizes the global clinical burden of seasonal influenza among adults aged ≥ 65 years. METHODS: An electronic database search was conducted and supplemented with a conference abstract search. Included studies described clinical outcomes in the ≥ 65 years population across several global regions and were published in English between January 1, 2012 and February 9, 2022. RESULTS: Ninety-nine publications were included (accounting for > 156,198,287 total participants globally). Clinical burden was evident across regions, with most studies conducted in the USA and Europe. Risk of influenza-associated hospitalization increased with age, particularly in those aged ≥ 65 years living in long-term care facilities, with underlying comorbidities, and infected with A(H3N2) strains. Seasons dominated by circulating A(H3N2) strains saw increased risk of influenza-associated hospitalization, intensive care unit admission, and mortality within the ≥ 65 years population. Seasonal differences in clinical burden were linked to differences in circulating strains. CONCLUSIONS: Influenza exerts a considerable burden on adults aged ≥ 65 years and healthcare systems, with high incidence of hospitalization and mortality. Substantial influenza-associated clinical burden persists despite increasing vaccination coverage among adults aged ≥ 65 years across regions included in this review, which suggests limited effectiveness of currently available seasonal influenza vaccines. To reduce influenza-associated clinical burden, influenza vaccine effectiveness must be improved. Next generation vaccine production using mRNA technology has demonstrated high effectiveness against another respiratory virus-SARS-CoV-2-and may overcome the practical limitations associated with traditional influenza vaccine production.

Whole-Genome Analysis of Influenza A(H3N2) and B/Victoria Viruses Detected in Myanmar during the COVID-19 Pandemic in 2021.

An influenza circulation was observed in Myanmar between October and November in 2021. Patients with symptoms of influenza-like illness were screened using rapid diagnostic test (RDT) kits, and 147/414 (35.5%) upper respiratory tract specimens presented positive results. All RDT-positive samples were screened by a commercial multiplex real-time polymerase chain reaction (RT-PCR) assay, and 30 samples positive for influenza A(H3N2) or B underwent further typing/subtyping for cycle threshold (Ct) value determination based on cycling probe RT-PCR. The majority of subtyped samples (n = 13) were influenza A(H3N2), while only three were B/Victoria. Clinical samples with low Ct values obtained by RT-PCR were used for whole-genome sequencing via next-generation sequencing technology. All collected viruses were distinct from the Southern Hemisphere vaccine strains of the corresponding season but matched with vaccines of the following season. Influenza A(H3N2) strains from Myanmar belonged to clade 2a.3 and shared the highest genetic proximity with Bahraini strains. B/Victoria viruses belonged to clade V1A.3a.2 and were genetically similar to Bangladeshi strains. This study highlights the importance of performing influenza virus surveillance with genetic characterization of the influenza virus in Myanmar, to contribute to global influenza surveillance during the COVID-19 pandemic.

Outcomes of vaccinations against respiratory diseases in patients with end-stage renal disease undergoing hemodialysis: A systematic review and meta-analysis.

Due to the nature of the disease, end-stage renal disease (ESRD) patients suffer from dysfunction of the adaptive immune system, which leads to a poorer response to vaccination. Accordingly, it is crucial to evaluate the efficacy and safety of management strategies, including vaccinations, which could potentially reduce the risk of respiratory diseases, such as pneumonia, influenza, or COVID-19, and its associated outcomes. We searched PubMed, CENTRAL, ScienceDirect, Scopus, ProQuest, and Google Scholar databases using designated MeSH keywords. The risk of bias was assessed using ROBINS-I. The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Relative risk (RR) and 95% confidence interval (CI) were calculated. Heterogeneity was investigated using forest plots and I2 statistics. This systematic review included a total of 48 studies, with 13 studies of influenza (H1N1 and H3N2) vaccination and 35 studies of COVID-19 vaccination. H1N1 vaccination in ESRD patients undergoing hemodialysis induced lower seroconversion rates (RR 0.62, 95% CI: 0.56-0.68, p <0.00001) and lower seroprotection rates (RR 0.76, 95% CI: 0.70-0.83, p <0.00001) compared to controls. H3N2 vaccination in ESRD patients undergoing hemodialysis yielded lower seroconversion rates (RR 0.76, 95% CI: 0.68-0.85, p <0.00001) and lower seroprotection rates (RR 0.84, 95% CI: 0.77-0.90, p <0.00001) compared to controls. Twenty-nine studies demonstrate significantly lower antibody levels in ESRD patients undergoing hemodialysis compared to the controls following COVID-19 vaccination. This review presents evidence of lower seroconversion and seroprotection rates after vaccination against viral respiratory diseases in patients with ESRD undergoing hemodialysis. Since hemodialysis patients are more susceptible to infection and severe disease progression, a weakened yet substantial serological response can be considered adequate to recommend vaccination against respiratory diseases in this population. Vaccination dose, schedule, or strategy adjustments should be considered in stable ESRD patients on maintenance hemodialysis. Trial registration: Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255983, identifier: CRD42021255983.

Synthesis and biological evaluation of new ß-D-N4-hydroxycytidine analogs against SARS-CoV-2, influenza viruses and DENV-2.

Drug repurposing approach was applied to find a potent antiviral agent against RNA viruses such as SARS-CoV-2, influenza viruses and dengue virus with a concise strategy of small change in parent molecular structure. For this purpose, ß-D-N4-hydroxycytidine (NHC, 1) with a broad spectrum of antiviral activity was chosen as the parent molecule. Among the prepared NHC analogs (8a-g, and 9) from uridine, ß-D-N4-O-isobutyrylcytidine (8a) showed potent activity against SARS-CoV-2 (EC50 3.50 µM), Flu A (H1N1) (EC50 5.80 µM), Flu A (H3N2) (EC50 7.30 µM), Flu B (EC50 3.40 µM) and DENV-2 (EC50 3.95 µM) in vitro. Furthermore, its potency against SARS-CoV-2 was >5-fold, 3.4-fold, and 3-fold compared to that of NHC (1), MK-4482 (2), and remdesivir (RDV) in vitro, respectively. Ultimately, compound 8a was expected to be a potent inhibitor toward RNA viruses as a viral mutagenic agent like MK-4482.