Circulating Influenza Viruses Research Articles

Comparative Analysis of Clinical and Epidemiological Characteristics in Patients with SARI Confirmed as Influenza or COVID-19 Admitted in a Tertiary Care Hospital in Bucharest, Romania

The COVID-19 pandemic has influenced the epidemiology of other respiratory pathogens, and this was most evident in the 2020–2021 season, which was characterized by a low circulation of influenza viruses. We aim to present a comparative analysis of clinical and epidemiological characteristics of 2018–2019 influenza cases and 2020–2021 COVID-19 cases, hospitalized at a tertiary infectious diseases hospital in Bucharest. We used data collected from patients admitted for severe acute respiratory infection (SARI) and subsequently confirmed with either influenza or COVID-19. During the 2018–2019 season, 208 patients over 18 years of age were confirmed with influenza (median age = 53 years, 59.6% were female) and 6.7% had been vaccinated against influenza. The most frequent symptoms were fever (97.1%) and cough (94.7%), and 77.4% had at least one chronic condition. 90.4% received influenza antiviral therapy. During the 2020–2021 season, 191 patients were confirmed with COVID-19 (median age = 56 years, 67% were male). The most frequent symptoms were cough (85.9%) and fever (80.6%), and 75.9% had at least one chronic condition. This analysis highlights the main similarities and differences between influenza and COVID-19 and could help to optimize the management of cases.

Circulation of influenza A viruses among patients hospitalized for severe acute respiratory infection in a tertiary care hospital in Romania in the 2018/19 season: Results from an observational descriptive epidemiological study.

The seasonal circulation of influenza viruses and the impact that this infection has on the population varies from year to year. We have prospectively captured hospital-based surveillance data describing the circulation of influenza viruses and characterizing patients with influenza admitted to a tertiary hospital in Bucharest, Romania in the 2018/19 season.We have conducted an observational descriptive epidemiological study analyzing all consecutive patients hospitalized for influenza like illness or severe acute respiratory infection at the National Institute for Infectious Diseases “Prof. Dr. Matei Balş”, Bucharest, Romania, from November 2018 to April 2019. For all patients we actively collected standardized clinical information and performed real-time reverse transcription polymerase chain reaction testing of respiratory samples to identify the presence of influenza viruses and to determine the subtype/lineage.A total of 1128 hospitalized patients were tested in this study, with an influenza positivity rate of 41.2% (n = 465). We identified an exclusive circulation of influenza A viruses (A/H1 – 57.2%, A/H3 – 29.3%, A not subtyped – 13.3%), with only 1 case of influenza B detected at the end of the season (week 18/2019). Children under 5 years of age accounted for the majority of cases (40%, n = 186), and all cases had a favorable evolution. Females were more likely to test positive for influenza (53.3%) compared to males (46.7%), P = .048, and presence of asthma or chronic obstructive pulmonary disease increased the risk of influenza 4.4-fold and 2-fold, respectively (P < .001 and P = .034). Thirteen influenza patients required hospitalization in intensive care and 5 deaths were recorded (1.1%). The vaccination rate for all patients included in the study was low (4.6%). The existence of chronic conditions or age over 65 years prolonged the hospitalization period with 2 days (P < .001 each).In the 2018/19 season, we identified an important circulation of influenza A viruses among patients hospitalized for influenza like illness/severe acute respiratory infection in a tertiary care hospital in Romania, with a higher likelihood of affecting females and patients with pre-existing lung conditions. Monitoring of the clinical and epidemiological characteristics of influenza virus infection is of great interest and should be done carefully each season to better inform on the necessary measures to limit the impact that this infection may have on risk groups.

154. Circulation of Rhinovirus/Enterovirus Respiratory Infections in Children During 2020-21 in the United States

BackgroundSharp declines in influenza and respiratory syncytial virus (RSV) circulation across the U.S. have been described during the pandemic in temporal association with community mitigation for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine relative frequencies of rhinovirus/enterovirus (RV/EV) and other respiratory viruses in children presenting to emergency departments or hospitalized with acute respiratory illness (ARI) prior to and during the COVID-19 pandemic. MethodsWe conducted a multi-center active prospective ARI surveillance study in children as part of the New Vaccine Surveillance Network (NVSN) from December 2016 through January 2021. Molecular testing for RV/EV, RSV, influenza, and other respiratory viruses [i.e., human metapneumovirus, parainfluenza virus (Types 1-4), and adenovirus] were performed on specimens collected from children enrolled children. Cumulative percent positivity of each virus type during March 2020–January 2021 was compared from March-January in the prior seasons (2017-2018, 2018-2019, 2019-2020) using Pearson’s chi-squared. Data are provisional.ResultsAmong 69,403 eligible children, 37,676 (54%) were enrolled and tested for respiratory viruses. The number of both eligible and enrolled children declined in early 2020 (Figure 1), but 4,691 children (52% of eligible) were enrolled and tested during March 2020-January 2021. From March 2020-January 2021, the overall percentage of enrolled children with respiratory testing who had detectable RV/EV was similar compared to the same time period in 2017-2018 and 2019-2020 (Figure 1, Table 1). In contrast, the percent positivity of RSV, influenza, and other respiratory viruses combined declined compared to prior years, (p< 0.001, Figure 1, Table 1). Figure 1. Percentage of Viral Detection Among Enrolled Children Who Received Respiratory Testing, New Vaccine Surveillance Network (NVSN), United States, December 2016 – January 2021 Table 1. Percent of Respiratory Viruses Circulating in March 2020– January 2021, compared to March-January in Prior Years, New Vaccine Surveillance Network (NVSN), United States, March 2017 – January 2021ConclusionDuring 2020, RV/EV continued to circulate among children receiving care for ARI despite abrupt declines in other respiratory viruses within this population. These findings warrant further studies to understand virologic, behavioral, biological, and/or environmental factors associated with this continued RV/EV circulation.Disclosures Jennifer E. Schuster, MD, Merck, Sharpe, and Dohme (Individual(s) Involved: Self): Grant/Research Support Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Claire Midgley, PhD, Nothing to disclose Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support

Epidemiological monitoring of avian influenza in the Republic of Crimea in 2019–2020

The paper presents results of avian influenza epidemiological monitoring in the Republic of Crimea in 2019–2020. The attention was focused on the study of water basins of the Azov and Black Seas, the Sivash Lagoon and freshwater lakes in the Feodosia Urban Okrug, Leninsky, Sovetsky, Nizhnegorsky, Chernomorsky and Saksky Raions to detect the avian influenza virus circulation. Examination of the above mentioned areas showed that some freshwater reservoirs became shallow and dry, and aquatic vegetation degraded. The natural biotope analysis conducted in 2019 and 2020 showed a decreased number of semiaquatic wild birds. The pathological material was sampled from semiaquatic and migratory wild birds, as well as from poultry kept in poultry farms and backyards. The collected samples were tested using real-time RT-PCR. In 2019, the AIV type A (H9) genome was detected in one fecal sample taken from wild birds near Kuchuk-Adzhigol Lake in Feodosia Urban Okrug. The AIV type A (H5) genome was detected in 2020 during laboratory testing of pathological material taken from the remains of a mute swan within the shoreline of a freshwater lake near the Ermakovo settlement of the Dzhankoysky Raion. The genetic analysis was performed in the FGBI “ARRIAH” (Vladimir), and the N8 subtype neuraminidase of the influenza virus isolate was determined. The comparative genetic analysis of 258 bp nucleic acid sequences of the AIV H gene fragment showed that the identified isolate belongs to the Asian genetic lineage of highly pathogenic AIV subtype H5 (clade 2.3.4.4) associated with the epidemic spread in Asia, Europe, the Middle East and Africa in 2016–2020.

A systematic approach to illuminate a new hot spot of avian influenza virus circulation in South Vietnam, 2016-2017.

In South Vietnam, live bird markets (LBMs) are key in the value chain of poultry products and spread of avian influenza virus (AIV) although they may not be the sole determinant of AIV prevalence. For this reason, a risk analysis of AIV prevalence was conducted accounting for all value chain factors. A cross-sectional study of poultry flock managers and poultry on backyard farms, commercial (high biosecurity) farms, LBMs and poultry delivery stations (PDSs) in four districts of Vinh Long province was conducted between December 2016 and August 2017. A total of 3597 swab samples were collected from birds from 101 backyard farms, 50 commercial farms, 58 sellers in LBMs and 19 traders in PDSs. Swab samples were submitted for AIV isolation. At the same time a questionnaire was administered to flock managers asking them to provide details of their knowledge, attitude and practices related to avian influenza. Multiple correspondence analysis and a mixed-effects multivariable logistic regression model were developed to identify enterprise and flock manager characteristics that increased the risk of AIV positivity. A total of 274 birds were positive for AIV isolation, returning an estimated true prevalence of 7.6% [95% confidence interval (CI): 6.8%-8.5%]. The odds of a bird being AIV positive if it was from an LBM or PDS were 45 (95% CI: 3.4-590) and 25 (95% CI: 1.4-460), respectively, times higher to the odds of a bird from a commercial poultry farm being AIV positive. The odds of birds being AIV positive for respondents with a mixed (uncertain or inconsistent) level and a low level of knowledge about AI were 5.0 (95% CI: 0.20-130) and 3.5 (95% CI: 0.2-62), respectively, times higher to the odd of birds being positive for respondents with a good knowledge of AI. LBMs and PDSs should receive specific emphasis in AI control programs in Vietnam. Our findings provide evidence to support the hypothesis that incomplete respondent knowledge of AI and AIV spread mechanism were associated with an increased risk of AIV positivity. Delivery of education programs specifically designed for those in each enterprise will assist in this regard. The timing and frequency of delivery of education programs are likely to be important if the turnover of those working in LBMs and PDSs is high.

SARS-CoV-2 and influenza virus coinfection among patients with severe acute respiratory infection during the first wave of COVID-19 pandemic in Bangladesh: a hospital-based descriptive study

ObjectiveTo estimate the proportion of SARS-CoV-2 and influenza virus coinfection among severe acute respiratory infection (SARI) cases-patients during the first wave of COVID-19 pandemic in Bangladesh.DesignDescriptive study.SettingNine tertiary level hospitals...

Genetic Characterization and Pathogenesis of Three Novel Reassortant H5N2 Viruses in South Korea, 2018.

The outbreaks of H5N2 avian influenza viruses have occasionally caused the death of thousands of birds in poultry farms. Surveillance during the 2018 winter season in South Korea revealed three H5N2 isolates in feces samples collected from wild birds (KNU18-28: A/Wild duck/South Korea/KNU18-28/2018, KNU18-86: A/Bean Goose/South Korea/KNU18-86/2018, and KNU18-93: A/Wild duck/South Korea/KNU18-93/2018). Phylogenetic tree analysis revealed that these viruses arose from reassortment events among various virus subtypes circulating in South Korea and other countries in the East Asia–Australasian Flyway. The NS gene of the KNU18-28 and KNU18-86 isolates was closely related to that of China’s H10N3 strain, whereas the KNU18-93 strain originated from the H12N2 strain in Japan, showing two different reassortment events and different from a low pathogenic H5N3 (KNU18-91) virus which was isolated at the same day and same place with KNU18-86 and KNU18-93. These H5N2 isolates were characterized as low pathogenic avian influenza viruses. However, many amino acid changes in eight gene segments were identified to enhance polymerase activity and increase adaptation and virulence in mice and mammals. Experiments reveal that viral replication in MDCK cells was quite high after 12 hpi, showing the ability to replicate in mouse lungs. The hematoxylin and eosin-stained (H&E) lung sections indicated different degrees of pathogenicity of the three H5N2 isolates in mice compared with that of the control H1N1 strain. The continuing circulation of these H5N2 viruses may represent a potential threat to mammals and humans. Our findings highlight the need for intensive surveillance of avian influenza virus circulation in South Korea to prevent the risks posed by these reassortment viruses to animal and public health.

Active Surveillance for Highly Pathogenic Avian Influenza Viruses in Wintering Waterbirds in Northeast Italy, 2020-2021.

The increasing involvement of wild waterfowl in H5 Highly Pathogenic Avian Influenza Virus (HPAIV) circulation continues to pose a threat to animal and public health worldwide. In winter 2020–2021, two field surveillance activities were carried out on a weekly basis, through virological and serological analyses, in 823 hunted and 521 trapped migratory aquatic birds in northeast Italy. Sixty Eurasian teals were recaptured several times, which allowed us to follow the progression of the HPAI H5 infection in naturally infected wild waterfowl. Oropharyngeal, cloacal, and feather swabs (OS, CS and FS) were collected from each duck and tested by real time rRT-PCR Type A influenza. The identified viruses were characterized and pathotyped by sequencing. Several viruses belonging to three different HPAI H5 subtypes were detected: H5N8, H5N5, and H5N1. High prevalence of infection with HPAI H5 clade 2.3.4.4b during November–December 2020 (up to 27.1%) was observed in captured Eurasian teals, while infection rates in hunted dabbling ducks, mainly Eurasian wigeons, showed the highest prevalence of infection in November 2020 (8.9%) and January 2021 (10.2%). All HPAI positive birds were also clinically healthy when recaptured weeks apart. The OS and FS showed the highest detection efficiency of HPAIV. Our results highlight that HPAI passive surveillance should be complemented by a targeted active surveillance to more efficiently detect novel HPAI viruses.

Effect of inactivated influenza vaccination on human coronavirus infection: Secondary analysis of a randomized trial in Hutterite colonies

BackgroundAlthough influenza vaccines provide protection against influenza viruses, concern has been raised that they may increase susceptibility to non-influenza respiratory viruses. As pandemic lockdowns end, temporal overlap of circulation of seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expected. Understanding the impact of influenza vaccination on risk of coronavirus infection is therefore of considerable public health importance. MethodsWe performed a secondary analysis of a randomized trial where children and adolescents in Canadian Hutterite colonies were randomly assigned by colony to receive the 2008–2009 seasonal inactivated trivalent influenza vaccine (TIV) or a control hepatitis A (HepA) vaccine. All 3273 colony members (vaccinated children and nonvaccine recipients) were followed for the primary outcome of RT-PCR confirmed seasonal coronavirus infection. Serum collected pre- and post-vaccination was analyzed for titers of IgG antibodies towards human coronaviruses (HCoV). ResultsThe incidence of coronavirus infection was 0·18/1000 person-days in the colonies that received TIV vs 0.36/1000 person-days in the control group, hazard ratio (HR) 0.49 [0.21–1.17]. The risk reduction among non-vaccine recipients in the TIV group compared to the control group was HR 0.55 [0.24–1.23]. There was an increase in the geometric mean fold change of HCoV-OC43 antibody titers following TIV compared to HepA vaccine (mean difference 1.2 [0.38–2.06], p = 0.007), and an increase in geometric mean HCoV-NL63 antibody titers post-TIV (262.9 vs 342.9, p = 0.03). ConclusionThe influenza vaccine does not increase the risk of a coronavirus infection. Instead, the influenza vaccine may reduce the rate of coronavirus infections by inducing cross-reactive anti-coronavirus IgG antibodies.

Longitudinal Analysis of Influenza A(H5) Sero-Surveillance in Myanmar Ducks, 2006-2019.

Between 2006 and 2019, serological surveys in unvaccinated domestic ducks reared outdoors in Myanmar were performed, using a haemagglutination inhibition (HI) test, to confirm H5 avian influenza virus circulation and assess temporal and spatial distribution. Positive test results occurred every year that samples were collected. The annual proportion of positive farms ranged from 7.1% to 77.2%. The results revealed silent/sub-clinical influenza A (H5) virus circulation, even in years and States/Regions with no highly pathogenic avian influenza (HPAI) outbreaks reported. Further analysis of the 2018/19 results revealed considerable differences in seroconversion rates between four targeted States/Regions and between years, and showed seroconversion before and during the sampling period. By the end of the trial, a high proportion of farms were seronegative, leaving birds vulnerable to infection when sold. Positive results likely indicate infection with Gs/GD/96-lineage H5Nx HPAI viruses rather than other H5 subtype low-pathogenicity avian influenza viruses. The findings suggested persistent, but intermittent, circulation of Gs/GD/96-lineage H5Nx HPAI viruses in domestic ducks, despite the veterinary services’ outbreak detection and control efforts. The role of wild birds in transmission remains unclear but there is potential for spill-over in both directions. The findings of this study assist the national authorities in the design of appropriate, holistic avian influenza control programs.

Spotlight influenza: The 2019/20 influenza season and the impact of COVID-19 on influenza surveillance in the WHO European Region.

BackgroundAnnual seasonal influenza activity in the northern hemisphere causes a high burden of disease during the winter months, peaking in the first weeks of the year.AimWe describe the 2019/20 influenza season and the impact of the COVID-19 pandemic on sentinel surveillance in the World Health Organization (WHO) European Region.MethodsWe analysed weekly epidemiological and virological influenza data from sentinel primary care and hospital sources reported by countries, territories and areas (hereafter countries) in the European Region.ResultsWe observed co-circulation of influenza B/Victoria-lineage, A(H1)pdm09 and A(H3) viruses during the 2019/20 season, with different dominance patterns observed across the Region. A higher proportion of patients with influenza A virus infection than type B were observed. The influenza activity started in week 47/2019, and influenza positivity rate was ≥ 50% for 2 weeks (05–06/2020) rather than 5–8 weeks in the previous five seasons. In many countries a rapid reduction in sentinel reports and the highest influenza activity was observed in weeks 09–13/2020. Reporting was reduced from week 14/2020 across the Region coincident with the onset of widespread circulation of SARS-CoV-2.ConclusionsOverall, influenza type A viruses dominated; however, there were varying patterns across the Region, with dominance of B/Victoria-lineage viruses in a few countries. The COVID-19 pandemic contributed to an earlier end of the influenza season and reduced influenza virus circulation probably owing to restricted healthcare access and public health measures.

DYNAMICS OF CHILDHOOD RESPIRATORY INFECTIONS DURING THE COVID-19 PANDEMIC: THE EFFECT OF QUARANTINE АND BEYOND

Monitoring epidemic processes and the dynamics of the spread of infectious diseases is essential for predicting their distribution and effective planning in healthcare. The importance of studying seasonal trends in the spread of respiratory viral infections and the specific effects of non-pharmaceutical interventions in nationwide scales and the use of available vaccines stand out even more in the context of the coronavirus disease-19 (COVID-19) pandemic. Even if the dynamics of pediatric respiratory viral infections show some variation at the national and local levels, depending on health regulation, respiratory viral pathogens follow a typical pattern of incidence. Therefore, we hypothesize that anticipated reduction of the incidence of common respiratory viral infections would undoubtedly exert positive effects, such as ease of burdening healthcare that combates the COVID-19 pandemic. However, we suspect a shift in familiar seasonal characteristics of common respiratory viral infections. We also speculate that strict long-term limitations of the natural spread of respiratory viral infections can lead to the development of hard-to-predict epidemiological outliers. Additionally, the tricky balance between humanity’s natural impulse to return to normalcy and control the new and still dynamically evolving infection could lead to new threats from old and well-known pathogens. Finally, we hypothesize that the absence of regular influenza virus circulation may lead to a high mismatch rate and a significant reduction in flu vaccine efficacy.

Testing for genetic mutation of seasonal influenza virus

Influenza virus strains undergo genetic mutations every year and these changes in genetic makeup pose difficulties for effective vaccine selection. To better understand the problem it is important to statistically quantify the amount of genetic change between circulating strains from different years. In this paper, we propose the nonparametric crossmatch test applied to phylogenetic trees to assess the level of discrepancy between circulating flu virus strains between two years; the viruses being represented by a phylogenetic tree. The crossmatch test has advantages compared to parametric tests in that it preserves more information in the data. The outcome of the test would indicate whether the circulating influenza virus has mutated sufficiently in the past year to be considered as a new population of virus, suggesting the need to consider a new vaccine. We validate the test on simulated phylogenetic tree samples with varying branch lengths, as well as with publicly available virus sequence data from the ‘Global Initiative on Sharing All Influenza Data’ (GISAID: https://www.gisaid.org/)

Epidemiological and virological surveillance of Severe Acute Respiratory Infections in the 2019/2020 season in Siena, Tuscany, Italy.

SummaryBackgroundInfluenza is a major public health issue. Indeed, in Italy there were 7.6 million symptomatic cases of influenza in the 2019/2020 influenza season (from October 2019 to April 2020). The aim of this study is to analyse the circulation of influenza A and B viruses in hospitalized adult and elderly patients with Severe Acute Respiratory Infections (SARI) at Le Scotte University Hospital in Siena.MethodsOropharyngeal swabs were taken from SARI patients, who also completed a questionnaire recording their underlying diseases and vaccination status. Total RNA was extracted from each respiratory swab by means of the QIAamp Viral RNA Mini kit, and RT-PCR was carried out. All statistical analyses were performed by means of GraphPad Prism 6 software and STATA.ResultsIn this study we collected 68 swabs. The average age of subjects was 79.4 years (C.I.: 76.6-82.3) and 52.9% were female. The subjects had fever (89.7%), fatigue (77%), headache (47%), cough (75%), sore throat (70.5%), and breathlessness (63.2%). We found that 20% of the 68 subjects were positive (13% for A H3N2 and 7% for A H1N1). Of the 68 subjects, 25% had received a seasonal influenza vaccine (91.6% trivalent and 8.4% quadrivalent).ConclusionsOur study is important in order to determine the timing and spread of influenza viruses and track changes in circulating influenza viruses, so as to inform seasonal influenza vaccine composition. Seasonal vaccination is considered the most effective way to prevent influenza and its complications.

Likelihood of prior exposure to circulating influenza viruses resulting in cross-protection by CD8+ T cells against emergent H3N2v swine viruses infecting humans.

Outbreaks of influenza in swine can result in potential threats to human public health. A notable occurrence was the emergence of swine-origin H1N1 influenza viruses in 2009. Since then, there have been several documented outbreaks of swine-origin influenza infecting humans in several countries. Sustained events have occurred when H1N1v, H1N2v, and H3N2v swine-origin viruses have infected humans visiting agricultural shows in the US. The predominant H3N2v viruses gained the matrix protein from the A(H1N1)pdm09 viruses, with reported human-to-human transmission raising fears of another pandemic. Current vaccines do not induce secondary cell-mediated immune responses, which may provide cross-protection against novel influenza A subtypes, however, population susceptibility to infection with seasonal influenza is likely to be influenced by cross-reactive CD8+ T-cells directed towards immunogenic peptides derived from viral proteins. This study involved a retrospective review of historical influenza viruses circulating in human populations from 1918 to 2020 to identify evidence of prior circulation of H3N3v immunogenic CD8+ T-cells peptides found in the NP and M1 proteins. We found evidence of prior circulation of H3N2v NP and M1 immunogenic peptides in historical influenza viruses. This provides insight into the population context in which influenza viruses emerge and may help inform immunogenic peptide selection for cytotoxic T-cell lymphocytes (CTL)-inducing influenza vaccines. Next-generation vaccines capable of eliciting CD8+ T-cell-mediated cross-protective immunity may offer a long-term alternative strategy for influenza vaccines.

Interference of SARS-CoV-2 with other Respiratory Viral Infections agents during Pandemic

Background. Integrative epidemiological and etiological analysis of peculiarities of the development of the COVID-19 pandemic in different countries of the world is of significant scientific and practical interest in order to improve the preparedness of medical and social services during the upcoming pandemics. The purpose of the research. To determine the features of the epidemic process caused by a new coronavirus infection COVID-19, in all the diversity of its interaction with influenza viruses and other ARVI agents in the Russian Federation.Materials and methods. The studies were performed in the system of routine influenza surveillance by the Federal Center for Influenza and ARI at the Smorodintsev Research Institute of Influenza and the Center for Ecology and Epidemiology of Influenza at the National Center for Epidemiology and Microbiology named after N.F. Gamaleya, in cooperation with Regional Collaborating Base Laboratories in accordance with the Order of the Federal Service for Consumer Rights Protection Surveillance and Human Well-being No. 373 of March 31, 2005. Information on morbidity and hospitalization was provided by the erritorial Departments of Rospotrebnadzor. Information on the results of PCR detection of influenza and ARVI viruses, including SARS-CoV-2, was received from the «enters for Hygiene and Epidemiology" and was entered on-line into the electronic database of the Smorodintsev Research Institute of Influenza of the Ministry of Health of Russia. «AmpliSens reagent kits produced by the Central Research Institute of Epidemiology were used for PCR detection and subtyping of influenza A and B viruses, to identify ARVI agents, for PCR diagnosis of COVID-19 the kits certified in the Russian Federation of various producers were used.Results. It has been established that the annual epidemics of influenza, as well as the development of the second wave of the COVID- 19 pandemic in the season 2020–2021 was preceded pronounced increase of incidence rate (55.0 - 67.9 per 10,000), associated with rhinoviruses activity, starting from the week 38 to week 43. 2020, which reached on the peak 23–29.0% of patients examined. The increase of COVID-19 activity in the fall of 2020 began from week 41 with the peak (26.6–31.3%) of detection in the period from the week 47.2020 to week 4. 2021. The duration and severity of COVID-19 diseases, requiring hospitalization, distinguished the SARS-CoV-2 pandemic from influenza epidemics/pandemics. Significant changes in the nature of the epidemic process were found in the analysis of the age structure of morbidity and hospitalization – their distinct decrease in children's age groups against the background of pronounced growth among patients of the age group 15–64 yrs and, especially, in elderly people ≥ 65 yrs. The incidence growth curves coincided in time with an increase in SARS-CoV-2 activity against the background of a decrease in the detection frequency of other ARVI pathogens, including influenza and RSV viruses, as a result of pronounced interference between pathogens. Interestingly, as the frequency of SARS-CoV-2 detection decreased to 15–19%, the activity of rhinoviruses, seasonal coronaviruses and metapneumoviruses began to increase again from 0.7–3.0% to 5.6–6.6%, which indicated the existence of a quantitative relationship between the interference indicators of SARS-CoV-2 with other ARI agents. It was most clearly manifested in relation to influenza and RSV viruses, which detection in general for the season dropped to 0.04% and 0.3% respectively.Conclusions. The phenomenon of interference of SARS-CoV-2 with other viral respiratory agents was established, based on the facts of a sharp suppression of the circulation of influenza viruses, respiratory syncytial virus and other ARVI pathogens during the period of active spread of the pandemic coronavirus. A distinctive feature of the SARS-CoV-2 pandemic, in comparison with influenza epidemics, was its long duration and the severity of the diseases caused by that virus. During the period of the pandemic, a clear decrease in the incidence and hospitalization among children was revealed, with their pronounced growth in adults and, especially, in older people ≥ 65 years old.

Excess Invasive Meningococcal Disease Associated With Seasonal Influenza, South Africa, 2003-2018.

BackgroundInvasive meningococcal disease (IMD) is a devastating illness with high mortality rates. Like influenza, endemic IMD is seasonal, peaking in winter. Studies suggest that circulation of influenza virus may influence the timing and magnitude of IMD winter peaks.MethodsThis ecological study used weekly data from 2 nationwide surveillance programs: Viral Watch (proportion of outpatient influenza-positive cases from throat or nasal swab samples) and GERMS-SA (laboratory-confirmed cases of IMD), occurring across South Africa from 2003 through 2018 in all age bands. A bivariate time series analysis using wavelet transform was conducted to determine cocirculation of the diseases and the time lag between the peak seasons. We modeled excess meningococcal disease cases attributable to influenza cocirculation, using univariate regression spline models. Stata and R statistical software packages were used for the analysis.ResultsA total of 5256 laboratory-confirmed IMD cases were reported, with an average annual incidence of 0.23 episodes per 100 000 population and a mean seasonal peak during week 32 (±3 weeks). Forty-two percent of swab samples (10 421 of 24 741) were positive for influenza during the study period. The mean peak for all influenza occurred at week 26 (±4 weeks). There was an average lag time of 5 weeks between annual influenza and IMD seasons. Overall, 5% (1%–9%) of IMD cases can be attributable to influenza cocirculation, with, on average, 17 excess IMD cases per year attributable to influenza.ConclusionsA quantifiable proportion of IMD in South Africa is associated with influenza cocirculation; therefore, seasonal influenza vaccination may have an effect on preventing a small portion of IMD in addition to preventing influenza.

Surveillance on respiratory diseases reveals enzootic circulation of both H5 and H9 avian influenza viruses in small-scale commercial layer farms of Bangladesh.

Poultry production in Bangladesh has been experiencing H5N1 highly pathogenic avian influenza (HPAI) and H9N2 low pathogenic avian influenza (LPAI) for the last 14years. Vaccination of chickens against H5 HPAI is in practice since the end of 2012. Subsequently, the official reporting of HPAI outbreaks gradually decreased. However, the true extent of circulation of avian influenza virus (AIV) in commercial poultry production is not clear. To explore this, we conducted active surveillance in 422 small-scale commercial layer farms in 20 villages of Mymensingh and Tangail districts of Bangladesh during 2017 and 2018 for the presence of diseases with respiratory signs. A total of 88 farms with respiratory disease problems were identified and investigated during the surveillance. In addition, 22 small-scale commercial layer farms in the neighbouring areas with respiratory disease problem were also investigated on request from the farmers. Pooled samples of oropharyngeal swabs from live birds or respiratory tissues from dead birds of the farm suffering from respiratory disease problem were tested for molecular detection of avian influenza virus (AIV), Newcastle disease virus (NDV), infectious bronchitis virus (IBV), infectious laryngotracheitis virus (ILTV), Mycoplasma gallisepticum and Avibacterium paragallinarum. A total of 110 farms (88 in the surveillance site and 22 in the neighbouring region) were investigated, and one or more respiratory pathogens were detected from 89 farms. AIV was detected in 57 farms often concurrently with other pathogens. Among these 57 farms, H5, H9, both H5 and H9 or non-H5 and non-H9 AIV were detected in 28, 9, 13 or 7 farms, respectively. Birds of most of the H5 AIV-positive farms did not present typical clinical signs or high mortality. Twenty such farms were observed longitudinally, which had only 1.05%-5.50% mortality but a marked drop in egg production. This widespread circulation of H5 AIV along with H9 AIV and other pathogens in small-scale commercial layer farms, often with low mortality, reaffirms the enzootic circulation of AIV in Bangladesh, which may escape syndromic surveillance focused on unusual mortality only. To reduce public health risks, strengthening of the control programme with comprehensive vaccination, enhanced biosecurity, improved surveillance and outbreak response is suggested.

Genetic characterisation of the influenza viruses circulating in Bulgaria during the 2019\u20132020 winter season

Influenza viruses have a high potential for genetic changes. The objectives of this study were to analyse influenza virus circulation in Bulgaria during the 2019/2020 season, to perform a phylogenetic and molecular analyses of the haemagglutinin (HA) and neuraminidase (NA) sequences of representative influenza strains, and to identify amino acid substitutions compared to the current vaccine strains. Seasonal influenza viruses A(H3N2), A(H1N1)pdm09 and B/Victoria-lineage were detected using a real-time RT-PCR in 323 (23.3%), 149 (10.7%) and 138 (9.9%) out of 1387 patient samples studied, respectively. The HA genes of A(H3N2) viruses analysed belonged to clades 3C.3a (21 strains) and 3C.2a (5 strains): subclades 3C.2a1b + T131K, 3C.2a1b + T135K-B and 3C.2a1b + T135K-A. The clade 3C.3a and subclade 3C.2a1b viruses carried 5 and 14–17 substitutions in HA, as well as 3 and 9 substitutions in NA, respectively, in comparison with the A/Kansas/14/2017 vaccine virus, including some substitutions in the HA antigenic sites A, B, C and E. All 21 A(H1N1)pdm09 viruses sequenced fell into 6B.1A5A subclade. Amino acid sequence analysis revealed the presence of 7–11 substitutions in HA, compared to the A/Brisbane/02/2018 vaccine virus, three of which occurred in antigenic site Sb, along with 6–9 changes at positions in NA. All 10 B/Victoria-lineage viruses sequenced belonged to clade 1A with a triple deletion in HA1 (genetic group 1A(Δ3)B) and carried 7 and 3 substitutions in HA and NA, respectively, with respect to the B/Colorado/06/2017 vaccine virus. The results of this study confirm the rapid evolution of influenza viruses and the need for continuous antigenic and genetic surveillance.

Safety and immunogenicity of a quadrivalent inactivated subunit non-adjuvanted influenza vaccine: A randomized, double-blind, active-controlled phase 1 clinical trial

Quadrivalent influenza inactivated vaccine (IIV4) is more likely to provide wider protection against yearly circulating influenza viruses than trivalent inactivated influenza vaccine (IIV3). In this study, a total of 320 participants were allocated to four age cohorts (6–35 months, 3–8 years, 9–17 years, and ≥ 18 years; 80 participants/cohort) according to their actual date of birth. Participants in each cohort were randomly assigned to two groups to receive intramuscular injection of the trial vaccine or the comparative vaccine in a one-dose (3–8 years, 9–17 years,and ≥ 18 years) schedule on day 0 or two-dose (6–35 months cohort) schedule on day 0 and 28. The first objective is to evaluate the safety and immunogenicity of the full-dose subunit non-adjuvanted IIV4 (FD-subunit NAIIV4) we developed versus an active-control, China-licensed split-virion NAIIV4, in people ≥ 3 years. The second objective is to evaluate the safety and immunogenicity of FD-subunit NAIIV4 versus the half-dose (HD-subunit NAIIV4) in toddlers aged 6–35 months. Results showed that all adverse reactions noted were rare, mild, and self-limited. In ≥ 3 years cohorts, systemic adverse reactions in FD-subunit NAIIV4 groups were less than the active control split-virion NAIIV4 groups ([Systemic adverse reaction rates (95%CI)], 15.0 (8.6–21.4) versus 19.2(12.1–26.2), p = 0.391). The overall seroprotection efficacy after vaccination were comparable between FD-subunit NAIIV4 and the active control split-virion NAIIV4([Seroprotection rates (95%CI)], H1N1, 99.2(81.3–100.0) versus 94.9(90.9–98.9), p = 0.117; H3N2, 81.7(74.7–88.6) versus 82.1(75.1–89.0), p = 0.939; BV, 75.8(68.2–83.5) versus 74.4(66.4–82.3), p = 0.793; BY, 94.2(90.0–98.4) versus 92.3(87.5–97.1), p = 0.568). Additionally, FD-subunit NAIIV4 has comparable safety and better seroprotection versus that of the half-dose in 6–35 months toddlers groups ([Total adverse reaction rates (95%CI)], 37.5(18.5–56.5) versus 47.5(26.1–68.9), p = 0.366) ([Seroprotection rates (95%CI)], H1N1, 85(56.4–100.0) versus 75.7(47.6–100.0), p = 0.117; H3N2, 50(28.1–71.9) versus 29.7(12.2–47.3), p = 0.070; BV, 75(48.2–100.0) versus 29.7(12.2–47.3), p < 0.001; BY, 75(48.2–100.0) versus 56.8(32.5–81.0), p = 0.091). As a result, the FD-subunit NAIIV4 we developed is safe and effective to provide broader and adequate protection against the circulating influenza viruses during 2018–2019, which could be an essential component of the global preventive strategy for influenza pandemic.