Subtype H3N2 Influenza A Viruses: An Unmet Challenge in the Western Pacific

Subtype H3N2 influenza A viruses (A(H3N2)) have been the dominant strain in some countries in the Western Pacific region since the 2009 influenza A(H1N1) pandemic. Vaccination is the most effective way to prevent influenza; however, low vaccine effectiveness has been reported in some influenza seasons, especially for A(H3N2). Antigenic mismatch introduced by egg-adaptation during vaccine production between the vaccine and circulating viral stains is one of the reasons for low vaccine effectiveness. Here we review the extent of this phenomenon, the underlying molecular mechanisms and discuss recent strategies to ameliorate this, including new vaccine platforms that may provide better protection and should be considered to reduce the impact of A(H3N2) in the Western Pacific region.

Bioassay-Guided Fractionation of Siparuna glycycarpa n-Butanol Extract with Inhibitory Activity against Influenza A(H1N1)pdm09 Virus by Centrifugal Partition Chromatography (CPC)

Siparuna glycycarpa occurs in the Amazon region, and some species of this genus are used in Brazilian folk medicine. A recent study showed the inhibitory effect of this species against influenza A(H1N1)pdm09 virus, and in order to acquire active fractions, a polar solvent system n-butanol-methanol-water (9:1:10, v/v) was selected and used for bioassay-guided fractionation of n-butanol extract by centrifugal partition chromatography (CPC). The upper phase was used as stationary phase and the lower phase as mobile (descending mode). Among the collected fractions, the ones coded SGA, SGC, SGD, and SGO showed the highest antiviral inhibition levels (above 74%) at 100 µg·mL−1 after 24 h of infection. The bioactive fractions chemical profiles were investigated by LC-HRMS/MS data in positive and negative ionization modes exploring the Global Natural Products Social Molecular Networking (GNPS) platform to build a molecular network. Benzylisoquinoline alkaloids were annotated in the fractions coded SGA, SGC, and SGD collected during elution step. Aporphine alkaloids, O-glycosylated flavonoids, and dihydrochalcones in SGO were acquired with the change of mobile phase from lower aqueous to upper organic. Benzylisoquinolinic and aporphine alkaloids as well as glycosylated flavonoids were annotated in the most bioactive fractions suggesting this group of compounds as responsible for antiviral activity.

Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1)

Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan–Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).

Seroprevalence and Molecular Detection of Influenza A Virus (H1N1) in Sulaimani Governorate-Iraq

Influenza A (H1N1) virus is now rapidly scattering across the world. Early detection is one of the most effective measures to stop the further spread of the virus. The current study was aimed to detect influenza A (H1N1) serologically and by polymerase chain reaction (PCR) techniques. From September 2020 to June 2021, three hundred nasopharyngeal swabs and blood samples were collected from Hiwa and Shahid Tahir Hospitals in Sulaimani city. Obtained results revealed that 23.3% of the tested patients were seropositive anti-IgG for Influenza A, while 13.3% showed anti-IgM seropositive results although 10% of the tested cases were with both anti-IgG and anti-IgM seropositive results. Gender, residency, and flu symptoms showed no significant relations with seropositive results (p<0.05) whereas valuable relations were found between seropositive observations and smoking, the previous history of chronic diseases as well as employment status (p<0.05). It was concluded that hematologic investigations (CBC) were not dependable if H1N1 diagnosis and detection. Only 1% of the tested samples showed positive results for influenza A (H1N1) RNA using reverse transcription-PCR.

Influenza Vaccine Effectiveness Estimates among US Department of Defense Adult Beneficiaries over Four Consecutive Influenza Seasons: A Test-Negative Design Study with Different Control Groups

A test-negative design study with different control groups (influenza test-negative controls, non-influenza virus positive controls, and pan-negative controls) was conducted to assess inactivated influenza vaccine effectiveness (VE) in adults aged ≥18 years, 2016–2017 through 2019–2020 influenza seasons. A database was developed from the US Department of Defense Global Respiratory Pathogen Surveillance Program. VE was estimated using a generalized linear mixed model with logit link and binomial distribution, adjusted for confounding effects. A total of 7114 adults including 2543 medically attended, laboratory-confirmed influenza-positive cases were identified. Using influenza test-negative controls, the adjusted VE in adults was 40% [95% confidence interval (CI): 33–46%] overall, including 46% (95% CI: 36–55%) for influenza A(H1N1)pdm09, 32% (95% CI: 19–42%) for influenza A(H3N2), and 54% (95% CI: 44–62%) for influenza B. The age-stratified analysis showed that VE estimates against influenza A(H1N1)pdm09 (34%; 95% CI: −29–66%) and influenza A(H3N2) (6%; 95% CI: −60–45%) were low and non-significant for elderly adults ≥65 years of age. Overall VE estimates against any influenza or by influenza (sub)types in adults were consistent when using influenza test-negative controls, non-influenza virus positive controls, and pan-negative controls. Inactivated influenza vaccination provided moderate protection against influenza virus infection, based on the analysis from a large number of adults aged ≥18 years over multiple influenza seasons.

Influence of the ways of spreading influenza epidemics across the territory Russia on the peculiarities of the epidemic process in various Federal districts

Aims. Show the ways of spreading influenza epidemics across the territory of Russia over a long period (1968–2019) and their influence on the incidence of influenza and ARVI in total and separately influenza A (H1N1), A (H3N2) and B in the Federal Districts in the period from 2009 to 2019.Materials and methods. The analysis of influenza epidemics was carried out according to the computer database of the National center for influenza.Results. A retrospective analysis of influenza epidemics shows the absence of inter-epidemic seasons after 1986, the increase in epidemics of mixed etiology and different routes of entry and spread of influenza viruses in Russia. During the circulation of the influenza A (H1N1)pdm09 virus, influenza epidemics were mainly of mixed etiology. The main causative agents of epidemics entered the territory of Russia more often from the west and in both ways, and from the west and from the east. In the next season, the main pathogen changed, and the path of the virus circulating in the previous season also changed. Influenza viruses of different types A and B usually diverged in time. Influenza viruses of the same type A, but of different subtypes, usually spread in different directions, with one of them having a limited distribution in the districts. The tendency of greater intensity of the epidemic process in the districts involved in the epidemic first is shown.Conclusions. 2009 to 2019 the incidence was higher in the Northwestern and Ural districts of the European part of Russia. One of the reasons for the high morbidity in these districts is the predominance of the western route of influenza viruses entering the territory of Russia and the high intensity of the epidemic process in the districts that were the first to be involved in the epidemic.

Influenza A H1N1 mediated pre-existing immunity to SARS-CoV-2 predicts COVID-19 outbreak dynamics

Susceptibility to SARSCoV2 infections is highly variable, ranging from asymptomatic and mild infections in most, to deadly outcome in few. Here, we present evidence that antibodies induced by currently circulating influenza A H1N1 (flu) strains cross react with the most critical receptor binding motif of the SARSCoV2 spike protein that interacts with the ACE2 receptor. About 58 to 68% of blood donors in Stockholm had detectable antibodies to this cross-reactive peptide, NGVEGF, and seasonal flu vaccination trended to enhance binding of inhibitory antibodies to SARSCoV2. This peptide also activated CD8 T cells in 20% of healthy subjects. Eleven additional CD8 T cell peptides that cross react with flu and SARSCoV2 were identified that potentially protect against SARSCoV2 in 40 to 71% of individuals, depending on their HLA type.

Respiratory Viruses Among Ethnic Nicobarese During COVID-19 Pandemic

Background: Acute respiratory infections (ARIs) and severe acute respiratory illness (SARI) are public health burdens globally. The percentage of non-SARS CoV-2 respiratory viruses among patients having ARI and SARI who visit Car Nicobar's hospital settings is undocumented. Changes in the epidemiology of other respiratory viruses during COVID19 pandemic is being reported worldwide.Methods: Inpatient and outpatient settings at BJR hospital, Car Nicobar Island, India, were used to conduct prospective monitoring for ARI and SARI among Nicobarese tribal members. The patients with ARI and SARI were enlisted in BJR hospital from June 2019 to May 2021. At the ICMR-NIV in Pune, duplex qRTPCR assays were used to test the presence of respiratory viruses. The prevalence of non- SARS CoV-2 respiratory viruses was measured by comparing here between pandemic and pre-pandemic periods.Results: During the COVID19 pandemic, Influenza A (H3N2) (55.7%), and rhinovirus (12.5%) were predominantly reported non-SARS CoV-2 respiratory viruses while Human metapneumovirus (48.1%) and influenza A (H1N1)pdm09 (18.5%) were most commonly reported in the prepandemic period. This result indicates the altered circulation of non-SARS CoV-2 during pandemic.Conclusions: A considerable proportion of respiratory infection was correlated with respiratory viruses. Prevalence of non-SARS CoV-2 respiratory viruses was high at the time of infection when compared with pre-pandemic period, at Car Nicobar Island. This study enlightened the change in circulation of other respiratory viruses among the indigenous Nicobarese tribes. Clinicians and allied medical staff should be more prudent of these respiratory infections.

Can Major Public Health Emergencies Affect Changes in International Oil Prices?

In order to deepen the understanding of the impact of major public health emergencies on the oil market and to enhance the risk response capability, this study analyzed the logical relationship between major public health emergencies and international oil price changes, identified the change points, and calculated the probability of abrupt changes to international oil prices. Based on monthly data during six major public health emergencies from 2009 to 2020, this study built a product partition model. The results show that only the influenza A (H1N1) and COVID-19 pandemics were significant reasons for abrupt changes in international oil prices. Furthermore, the wild poliovirus epidemic, the Ebola epidemic, the Zika epidemic, and the Ebola epidemic in the Democratic Republic of the Congo had limited effects. Overall, the outbreak of a Public Health Emergency of International Concern (PHEIC) in major global economies has a more pronounced impact on international oil prices.

IMMUNOGRAPH-BASED ANALYSIS OF THE INFLUENZA A (H1N1)PDM09 VACCINE STRAIN IMMUNOGENICITY IN THE PANDEMIC AND POST-PANDEMIC PERIOD (2009-2014)

Currently, the assessment of the immunogenic properties of influenza viruses as a part of influenza vaccines, is carried out by using seroprotection, seroconversion as well as the rate of increases in post-vaccination antibodies. At the same time, significant differences in the immunogenicity of vaccines related to dynamic formation of high antibody titers responsible for long-term protection of the vaccinated, are neglected.Influenza viruses such as A (H1N1) pdm09 that caused 2009-2010 pandemic continue to circulate in the population, therefore, the assessment of the immunogenic activity of vaccine viruses prepared during the pandemic period is interesting in for the methodology to prepare pandemic vaccines to be used in various groups (adults, children, elderly people).Analyzing immunogenicity of influenza vaccines used during the 2009-10 swine influenza pandemic and the post-pandemic period up to the year 2014 was carried out by applying the graphical method for assessing immunogenicity (immunographs) measured as follows: for each group of vaccinated subjects (depending on the vaccine used), an increased rate in antibody level was calculated and the graphs of immunogenicity were plotted. An increased rate of serum antibodies magnitude from vaccinated subjects and the number of sera (in%) with a given fold increase rate in antibody level from 1 to the maximum magnitude were plotted on the x- and y-axis, respectively. The proposed method for assessing immunogenicity allows to plot immunogenicity graphs regardless of the serum antibodies level found in volunteers. The assessment described above revealed a several features for developing immune response to the pandemic virus A (H1N1)pdm09 such as the lack of immune response in a substantial number of adult volunteers (25-27%%) and young children (60-70%%) after monovaccine administration. The reason for such immune response can be both an insufficient dose of vaccine-containing viral antigen and suppressed immune response caused by the influenza A(H1N1)pdm09.A study on the immunogenic properties for seasonal influenza vaccines containing the influenza A (H1N1) pdm09 virus antigen in the years 2010 - 2014 revealed a variety in emerging humoral immunity ranging from a short-term, low-frequency increase in antibodies from vaccinated children to the formation of high antibody titers in elderly.Practically, immunographic analysis of influenza vaccines particularly those derived from the influenza A (H1N1)pdm09 virus, may result in proposing recommendations to increase an antigenic load at the beginning of a pandemic cycle and/or block the suppressive properties of vaccine-contained viruses in pediatric vaccines, because escalating virus dose in the vaccine may not always be achievable in this case.