Influenza virus inhibits respiratory syncytial virus (RSV) infection via a two-wave expression of interferon-induced protein with tetratricopeptide (IFIT) proteins

AbstractInfluenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance shows that RSV infection generally precedes influenza. However, in the last four winter seasons (2016-2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza virus inhibits RSV we performed coinfection of Human cervical carcinoma (HEp2) cells or mice with influenza and RSV and we observed that the influenza inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with tetratricopeptide (IFITs) family. Interestingly, in the second peak of upregulation, influenza viruses were no longer detectable in mouse lungs. We also observed that knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding of the interaction between influenza and RSV viruses and immune system involvement will contribute to the development and optimization of future treatment strategies against these viruses.Author SummaryRespiratory syncytial virus (RSV) and influenza viruses are both respiratory viruses associated with morbidity and mortality worldwide. RSV is usually detected in October, with a clear peak in December, whereas influenza virus arrives in November and peaks in January. In the last four seasons, influenza infection overlapped with that of RSV in Israel, which resulted in decreased morbidity of RSV suggesting that influenza virus inhibits RSV infection. To identify the mechanism responsible for the influenza inhibition of RSV we performed experiments in culture and in mice. We observed that influenza infection results in two wave modality of inhibition of RSV infection. Using mass spectrometry perfornmed on lungs from infected mice we show that influenza infection induces the expression of (IFIT) family of proteins which also showed a two-wave modality. Using knockdown and overexpression experiments we showed that indeed the IFTIs inhibits RSV infection. Our study provides new insights on the interaction between influenza and RSV viruses and immune system involvement and contribute to the development of future treatment strategies against these viruses.

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Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽

10.3390/v13020234 ◽

2021 ◽

Vol 13 (2) ◽

pp. 234

Author(s):

Sarah Al-Beltagi ◽

Cristian Alexandru Preda ◽

Leah V. Goulding ◽

Joe James ◽

Juan Pu ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Broad Spectrum ◽

Influenza A ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Virus Challenge ◽

2009 H1n1 ◽

Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

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Respiratory syncytial virus (RSV) in pediatric influenza-like illness (ILI) cases in Lombardy, Northern Italy, during seven consecutive winter seasons (from 2014-2015 to 2020-2021)

10.22541/au.163508928.85347830/v1 ◽

2021 ◽

Author(s):

Laura Pellegrinelli ◽

Cristina Galli ◽

Laura Bubba ◽

Arlinda Seiti ◽

Giovanni Anselmi ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Influenza Infection ◽

Northern Italy ◽

Influenza Viruses ◽

Influenza Surveillance ◽

Reference Laboratory ◽

Risk Of Infection ◽

Influenza Like Illness ◽

Rsv Infection ◽

Syncytial Virus

INTRODUCTION. Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract illness in young children and can also cause influenza-like illness (ILI). Here we investigated the epidemiological features of RSV infection in pediatric ILI cases in Lombardy (a region in Northern Italy accounting nearly 10-million inhabitants) from 2014-2015 to 2020-2021 winter seasons. MATERIAL AND METHODS. Data for this study were retrieved and statistically analyzed from the database of virological influenza surveillance of the regional reference laboratory for Lombardy within the Italian influenza surveillance network (InfluNet). RESULTS. RSV accounting for nearly 19% of pediatric ILI with a risk of infection nearly 2-fold greater than that of individuals ≥15 years. The RSV positivity rate increased to 28% considering 0-5 years old children. Although in children ≤5 years the risk of infection from influenza viruses resulted nearly 2-fold higher than the risk of RSV infection, the age group 4-6 months and 7-12 months showed 5-fold greater risk of infection from RSV than from influenza. Children ≤5 years of age with presence of one or more comorbidities had a nearly 5-fold greater risk of getting RSV infection than otherwise healthy 0-5 years old children. DISCUSSION. The use of the ILI sentinel surveillance allowed us to identify groups at higher risk of RSV and influenza infection and to define the start, duration, timing and intensity of the RSV and influenza community circulation, determining thresholds based on historical data. This surveillance approach can be implemented to assess the nearly real-time RSV circulation and impact.

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Circulation of Respiratory Viruses in Hospitalized Adults before and during the COVID-19 Pandemic in Brescia, Italy: A Retrospective Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18189525 ◽

2021 ◽

Vol 18 (18) ◽

pp. 9525

Author(s):

Maria Antonia De Francesco ◽

Caterina Pollara ◽

Franco Gargiulo ◽

Mauro Giacomelli ◽

Arnaldo Caruso

Keyword(s):

Respiratory Syncytial Virus ◽

Influenza A ◽

Statistical Significance ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Contact Tracing ◽

Nucleic Acid Detection ◽

Respiratory Pathogens ◽

Syncytial Virus ◽

Human Coronaviruses

Different preventive public health measures were adopted globally to limit the spread of SARS-CoV-2, such as hand hygiene and the use of masks, travel restrictions, social distance actions such as the closure of schools and workplaces, case and contact tracing, quarantine and lockdown. These measures, in particular physical distancing and the use of masks, might have contributed to containing the spread of other respiratory viruses that occurs principally by contact and droplet routes. The aim of this study was to evaluate the prevalence of different respiratory viruses (influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, 3 and 4, rhinovirus, adenovirus, metapneumovirus and human coronaviruses) after one year of the pandemic. Furthermore, another aim was to evaluate the possible impact of these non-pharmaceutical measures on the circulation of seasonal respiratory viruses. This single center study was conducted between January 2017–February 2020 (pre-pandemic period) and March 2020–May 2021 (pandemic period). All adults >18 years with respiratory symptoms and tested for respiratory pathogens were included in the study. Nucleic acid detection of all respiratory viruses was performed by multiplex real time PCR. Our results show that the test positivity for influenza A and B, metapneumovirus, parainfluenza virus, respiratory syncytial virus and human coronaviruses decreased with statistical significance during the pandemic. Contrary to this, for adenovirus the decrease was not statistically significant. Conversely, a statistically significant increase was detected for rhinovirus. Coinfections between different respiratory viruses were observed during the pre-pandemic period, while the only coinfection detected during pandemic was between SARS-CoV-2 and rhinovirus. To understand how the preventive strategies against SARS-CoV-2 might alter the transmission dynamics and epidemic patterns of respiratory viruses is fundamental to guide future preventive recommendations.

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Influenza A Virus Inhibits RSV Infection via a Two-Wave Expression of IFIT Proteins

Viruses ◽

10.3390/v12101171 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1171

Author(s):

Yaron Drori ◽

Jasmine Jacob-Hirsch ◽

Rakefet Pando ◽

Aharona Glatman-Freedman ◽

Nehemya Friedman ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Influenza Viruses ◽

Mass Spectrometry Analysis ◽

Influenza A Viruses ◽

Rsv Infection ◽

Syncytial Virus ◽

Mouse Lungs

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance has shown that RSV infection generally precedes influenza. However, in the last four winter seasons (2016–2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza A virus inhibits RSV, human cervical carcinoma (HEp2) cells or mice were co-infected with influenza A and RSV. Influenza A inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza A identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with the tetratricopeptide (IFITs) family. Interestingly, in the second wave, influenza A viruses were no longer detectable in mouse lungs. In addition, knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza A infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding the immune system involvement in the interaction between influenza A and RSV viruses will contribute to the development of future treatment strategies against these viruses.

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The burden of influenza and other respiratory viruses in hospitalized infants and children in a university hospital, Jordan

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2021.763 ◽

2021 ◽

Vol 16 ◽

Author(s):

Enas Al-Zayadneh ◽

Dina Mohammad Abu Assab ◽

Esraa Adeeb Arabiat ◽

Montaha Al-Iede ◽

Hanin Ahmad Kayed ◽

...

Keyword(s):

Influenza Virus ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Respiratory Viruses ◽

University Hospital ◽

Acute Lower Respiratory Infection ◽

Respiratory Pathogens ◽

Syncytial Virus ◽

Viral Surveillance ◽

Viral Respiratory

Background: Acute lower respiratory infection (ALRI) is a major cause of morbidity and mortality worldwide in young children and is predominately caused by viral respiratory pathogens. This study aims to identify the viral etiologies of acute ALRI in hospitalized children in Jordan University Hospital and compare the clinical characteristics of influenza virus infection with other respiratory viruses. Methods: a retrospective viral surveillance study that included 152 children below 15 years of age admitted with ALRI from December 2018 through April 2019. We recorded results of real-time reverse transcriptase-polymerase chain reaction (RT- PCR ) for common respiratory viruses. Clinical and demographic information of the study population was collected from patients’ electronic medical records. Results: 152 were identified with a median age of 1 year (mean was 2.1 years). Ninety-five patients (62.5%) were males. One or more viral respiratory pathogens were detected in 145 (95.3%) children. Respiratory syncytial virus was the most commonly detected virus in 68 patients (44.8%). Influenza virus was detected in 25 (16.4%). Children with influenza infection had more fever and less leukocyte count compared to children infected with other viruses. The severity of the ALRI correlated significantly with several factors, including age less than 6 months and the presence of neuromuscular disease (p<0.05). Conclusion: Viral detection was common among children admitted with viral ALRI. Viruses, including influenza, are recognized as major contributors to the morbidity associated with ALRI. More attention is needed on strategies for the prevention and detection of viral ALRI in developing countries.

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ACUTE CHEST SYNDROME with RESPIRATORY Syncytial VIRUS and SEASONAL INFLUENZA In CHILDREN with SICKLE CELL DISEASE

Blood ◽

10.1182/blood.v118.21.4845.4845 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4845-4845

Author(s):

John J. Strouse ◽

Sara C Sadreameli ◽

James F. Casella

Keyword(s):

Logistic Regression ◽

Risk Factor ◽

Respiratory Syncytial Virus ◽

Seasonal Influenza ◽

Influenza Infection ◽

Johns Hopkins Hospital ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Rsv Infection ◽

Syncytial Virus

Abstract Abstract 4845 Background: Respiratory syncytial virus (RSV) has been recognized as a cause of acute chest syndrome (ACS) in children with sickle cell disease (SCD). However, the proportion of children with RSV and SCD that are admitted to hospital or develop ACS is unknown. In studies of young children without SCD, RSV has traditionally been associated with more hospitalizations in the first three years of life then influenza has. To compare the relative severity of RSV vs. seasonal influenza in children with SCD, we compared the clinical characteristics and complications associated with these infections at a single tertiary care hospital. Methods: We defined a case as laboratory-confirmed RSV infection in a patient <18 years with SCD who was evaluated at Johns Hopkins Hospital from 1 September 1993 to June 30 2008. Through July 2006, we searched the discharge and billing databases for Johns Hopkins Hospital to identify those with SCD and laboratory testing for respiratory infections. Thereafter, we prospectively identified cases through divisional records. We confirmed the diagnosis of RSV by review of microbiology results in each patient's paper and/or electronic medical record. We used Fisher's exact test to compare proportions, Student's t-test or Wilcoxon rank-sum test to compare continuous variables, and logistic regression to evaluate associations. Results: We identified 47 patients with SCD and RSV and 76 with influenza during the study period. Clinical symptoms, such as reported fever (83% vs. 89%), cough (98% vs. 93%), and rhinorrhea (90% vs. 80%), were similar for RSV and influenza as were complications, including acute chest syndrome (Table). Treatments given for RSV and influenza including antibacterials (100% vs. 97%), transfusions (7% vs. 11%), and invasive ventilation (4% vs. 0%, p=0.15),with possibly more bronchodilator use for RSV (50% vs. 33%, p=0.055). In a multivariable logistic regression model, older age (OR 1.3 per year, 95% CI 1.04 –1.5, P=.02) and increased white blood cell count (WBC) at presentation (OR 1.2 per 1000/ul increase, 95% CI 1.03 – 1.4, P=0.02) were independently associated with increased risk of ACS in children with RSV. Discussion: Laboratory confirmed RSV infection was predominantly identified in infants and toddlers, while influenza infection was identified in children of all ages. This parallels RSV hospitalizations in the general population, where children are most likely to be hospitalized in the first few years of life. Both older age and high WBC at presentation may be a risk factor for more severe disease. This is unlikely to reflect referral bias (with only the sickest older children being referred for tertiary pediatric care) as a similar pattern was not seen for influenza infection. We conclude that RSV infection is often associated with ACS and similar in severity to influenza infection in children with SCD. An episode of ACS in the first three years of life was associated with more frequent ACS episodes later in childhood in the Dallas Newborn cohort. Since a significant proportion of patients with RSV develop ACS at a young age, RSV infection may represent a modifiable risk factor for recurrent ACS. An area for further study would be the efficacy or cost effectiveness of prevention of RSV-related hospitalizations. Palivizumab, a monoclonal antibody to RSV, has been shown to prevent complications related to RSV in other high risk groups and could be considered as an intervention in SCD that may decrease morbidity. Disclosures: No relevant conflicts of interest to declare.

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Differences in respiratory syncytial virus and influenza infection in a house-dust-mite-induced asthma mouse model: consequences for steroid sensitivity

Clinical Science ◽

10.1042/cs20130098 ◽

2013 ◽

Vol 125 (12) ◽

pp. 565-574 ◽

Cited By ~ 10

Author(s):

Hiroki Mori ◽

Nicole S. Parker ◽

Deborah Rodrigues ◽

Kathryn Hulland ◽

Deborah Chappell ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Virus Infection ◽

Mouse Model ◽

Influenza Infection ◽

Prednisolone Treatment ◽

Dust Mite ◽

Rsv Infection ◽

Ifn Γ ◽

Syncytial Virus ◽

Clinical Asthma

A significant number of clinical asthma exacerbations are triggered by viral infection. We aimed to characterize the effect of virus infection in an HDM (house dust mite) mouse model of asthma and assess the effect of oral corticosteroids. HDM alone significantly increased eosinophils, lymphocytes, neutrophils, macrophages and a number of cytokines in BAL (bronchoalveolar lavage), all of which were sensitive to treatment with prednisolone (with the exception of neutrophils). Virus infection also induced cell infiltration and cytokines. RSV (respiratory syncytial virus) infection in HDM-treated animals further increased all cell types in BAL (except eosinophils, which declined), but induced no further increase in HDM-elicited cytokines. However, while HDM-elicited TNF-α (tumour necrosis factor-α), IFN-γ (interferon-γ), IL (interleukin)-2, IL-5 and IL-10 were sensitive to prednisolone treatment, concomitant infection with RSV blocked the sensitivity towards steroid. In contrast, influenza infection in HDM- challenged animals resulted in increased BAL lymphocytes, neutrophils, IFN-γ, IL-1β, IL-4, IL-5, IL-10 and IL-12, but all were attenuated by prednisolone treatment. HDM also increased eNO (exhaled NO), which was further increased by concomitant virus infection. This increase was only partially attenuated by prednisolone. RSV infection alone increased BAL mucin. However, BAL mucin was increased in HDM animals with virus infection. Chronic HDM challenge in mice elicits a broad inflammatory response that shares many characteristics with clinical asthma. Concomitant influenza or RSV infection elicits differing inflammatory profiles that differ in their sensitivity towards steroids. This model may be suitable for the assessment of novel pharmacological interventions for asthmatic exacerbation.

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Seasonal Variations in Clostridium difficile Infections Are Associated with Influenza and Respiratory Syncytial Virus Activity Independently of Antibiotic Prescriptions: a Time Series Analysis in Québec, Canada

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05411-11 ◽

2011 ◽

Vol 56 (2) ◽

pp. 639-646 ◽

Cited By ~ 38

Author(s):

Rodica Gilca ◽

Élise Fortin ◽

Charles Frenette ◽

Yves Longtin ◽

Marie Gourdeau

Keyword(s):

Time Series ◽

Influenza Virus ◽

Respiratory Syncytial Virus ◽

Clostridium Difficile ◽

Seasonal Variations ◽

Respiratory Infections ◽

Respiratory Viruses ◽

Temporal Variations ◽

Average Delay ◽

Syncytial Virus

ABSTRACTSeasonal variations inClostridium difficile-associated diarrhea (CDAD), with a higher incidence occurring during winter months, have been reported. Although winter epidemics of respiratory viruses may be temporally associated with an increase in CDAD morbidity, we hypothesized that this association is mainly due to increased antibiotic use for respiratory infections. The objective of this study was to evaluate the effect of the two most frequent respiratory viruses (influenza virus and respiratory syncytial virus [RSV]) and antibiotics prescribed for respiratory infections (fluoroquinolones and macrolides) on the CDAD incidence in hospitals in the province of Québec, Canada. A multivariable Box-Jenkins transfer function model was built to relate monthly CDAD incidence to the monthly percentage of positive tests for influenza virus and RSV and monthly fluoroquinolone and macrolide prescriptions over a 4-year period (January 2005 to December 2008). Analysis showed that temporal variations in CDAD incidence followed temporal variations for influenza virus (P= 0.043), RSV (P= 0.004), and macrolide prescription (P= 0.05) time series with an average delay of 1 month and fluoroquinolone prescription time series with an average delay of 2 months (P= 0.01). We conclude that influenza virus and RSV circulation is independently associated with CDAD incidence after controlling for fluoroquinolone and macrolide use. This association was observed at an aggregated level and may be indicative of other phenomena occurring during wintertime.

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Rapid Molecular Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review of Diagnostic Accuracy and Clinical Impact Studies

Clinical Infectious Diseases ◽

10.1093/cid/ciz056 ◽

2019 ◽

Vol 69 (7) ◽

pp. 1243-1253 ◽

Cited By ~ 35

Author(s):

Laura M Vos ◽

Andrea H L Bruning ◽

Johannes B Reitsma ◽

Rob Schuurman ◽

Annelies Riezebos-Brilman ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Syncytial Virus ◽

Diagnostic Accuracy ◽

Respiratory Viruses ◽

Clinical Impact ◽

Risk Of Bias ◽

Cochrane Library ◽

Impact Studies ◽

Molecular Tests ◽

Syncytial Virus

Abstract We systematically reviewed available evidence from Embase, Medline, and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and Risk of Bias in Nonrandomized Studies of Interventions criteria for randomized and observational impact studies, respectively. Sixty-three DTA reports (56 studies) were meta-analyzed with a pooled sensitivity of 90.9% (95% confidence interval [CI], 88.7%–93.1%) and specificity of 96.1% (95% CI, 94.2%–97.9%) for the detection of either influenza virus (n = 29), respiratory syncytial virus (RSV) (n = 1), influenza virus and RSV (n = 19), or a viral panel including influenza virus and RSV (n = 14). The 15 included impact studies (5 randomized) were very heterogeneous and results were therefore inconclusive. However, we suggest that implementation of rapid diagnostics in hospital care settings should be considered.

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DETECTION OF INFLUENZA VIRUS AND PATHOGENS OF ACUTE RESPIRATORY VIRAL INFECTIONS IN POPULATION OF KAZAKHSTAN DURING 2018-2019 EPIDEMIC SEASON

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-doi-1348 ◽

2019 ◽

Author(s):

N. G. Klivleyeva ◽

N. S. Ongarbayeva ◽

A. M. Baimukhametova ◽

N. T. Saktaganov ◽

G. V. Lukmanova ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Syncytial Virus ◽

Influenza A ◽

Viral Infections ◽

Influenza Viruses ◽

Clinical Samples ◽

Type B ◽

Epidemic Season ◽

Parainfluenza Viruses ◽

Syncytial Virus

Influenza and other acute respiratory viral infections are the most common contemporary infectious diseases resulting in prominent harm to human health and great economic damage. At least five groups of viruses including more than 300 subtypes are currently referred to ARVI pathogens. Such infectious agents are characterized by variability resulting in their altered antigenic characteristics, increased contagiousness, "evasion from immune response and resistance to antivirals. Relevance of influenza and other ARVIs is also accounted for by rapid development of bacteria-associated respiratory diseases. Continuous variability of influenza viruses and emergence of new ARVI pathogens pose a serious threat. In recent years, a simultaneous circulation of subtype A (H1N1) and A (H3N2) influenza viruses with a predominance of a pandemic strain as well as type B viruses have been observed. Among the causative agents of non-influenza ARVIs, respiratory syncytial virus, rhino- and adenoviruses, and I/III parainfluenza viruses are recorded most often. Here we present the data of virology and serological examination of clinical samples collected during the 2018 – 2019 epidemic season in the Republic of Kazakhstan. For this, 2794 clinical samples (2530 nasopharyngeal swabs and 264 blood serums) were collected from patients diagnosed with ARVI, ARI, bronchitis, and pneumonia. Analysis of nasopharyngeal swabs for detection of influenza by RT-PCR demonstrated that mixed etiology influenza viruses with predominance of A/H1N1pdm virus circulated in Kazakhstan. The genetic fingerprints of influenza virus were found in 511 swabs (20.20% of total examined samples). Influenza A virus RNA was detected in 508 biological samples: A/H1N1 – in 289, A/H3N2 – in 209, and unidentified virus subtype in 10 samples. Type B influenza virus was detected in 3 samples. Study of 264 serum samples by HAI assay and ELISA showed emergence of antibodies against influenza A/H1N1, A/H3N2, and B viruses in residents from various regions of Kazakhstan that indirectly confirmed co-circulation of these viruses. 42 influenza virus strains were isolated in chicken embryos, from which 28 were assigned to A/H1N1pdm virus, 13 to A/H3N2 virus, and one isolate was identified as influenza B virus. Laboratory diagnostics of clinical samples for ARVIs established that among identified non-influenza agents respiratory syncytial virus dominated, while rhinoviruses and adenoviruses were less common. Metapneumoviruses, bocaviruses, coronaviruses, and type I parainfluenza viruses were detected in few cases. Comparison of study data with those obtained after examining circulation of influenza viruses during the 2017 – 2018 epidemic season showed that in 2018 – 2019 in Kazakhstan similar to the previous epidemic season, influenza A and B viruses continued to circulate, with prevalence of A/H1N1pdm virus. Identification of non-influenza viruses causing respiratory infections in 2018 – 2019 showed predominance of respiratory syncytial virus, which correlated with data on the 2017 – 2018 epidemic season.

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