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Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations.

ABSTRACT: This study compares the frequency and severity of influenza A/H1N1pdm09 (A/H1), influenza A/H3N2 (A/H3) and other respiratory virus infections in hospitalised patients. Data from 17 332 adult hospitalised patients admitted to Sir Charles Gairdner Hospital, Perth, Western Australia, with a respiratory illness between 2012 and 2015 were linked with data containing reverse transcription polymerase chain reaction results for respiratory viruses including A/H1, A/H3, influenza B, human metapneumovirus, respiratory syncytial virus and parainfluenza. Of these, 1753 (10.1%) had test results. Multivariable regression analyses were conducted to compare the viruses for clinical outcomes including ICU admission, ventilation, pneumonia, length of stay and death. Patients with A/H1 were more likely to experience severe outcomes such as ICU admission (OR 2.5, 95% CI 1.2-5.5, P = 0.016), pneumonia (OR 3.0, 95% CI 1.6-5.7, P < 0.001) and lower risk of discharge from hospital (indicating longer lengths of hospitalisation; HR 0.64 95% CI 0.47-0.88, P = 0.005), than patients with A/H3. Patients with a non-influenza respiratory virus were less likely to experience severe clinical outcomes than patients with A/H1, however, had similar likelihood when compared to patients with A/H3. Patients hospitalised with A/H1 had higher odds of severe outcomes than patients with A/H3 or other respiratory viruses. Knowledge of circulating influenza strains is important for healthcare preparedness.

SUBMITTER: Minney-Smith CA

PROVIDER: S-EPMC7003621 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations.

Minney-Smith C A CA Selvey L A LA Levy A A Smith D W DW

Epidemiology and infection 20191128

This study compares the frequency and severity of influenza A/H1N1pdm09 (A/H1), influenza A/H3N2 (A/H3) and other respiratory virus infections in hospitalised patients. Data from 17 332 adult hospitalised patients admitted to Sir Charles Gairdner Hospital, Perth, Western Australia, with a respiratory illness between 2012 and 2015 were linked with data containing reverse transcription polymerase chain reaction results for respiratory viruses including A/H1, A/H3, influenza B, human metapneumoviru ...[more]

PMID: 31775940

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Project description:BackgroundHuman influenza viruses are known to bind to sialic acid linked alpha2-6 to galactose, but the binding specificity beyond that linkage has not been systematically examined. H3N2 human influenza isolates lost binding to chicken red cells in the 1990s but viruses isolated since 2003 have re-acquired the ability to agglutinate chicken erythrocytes. We have investigated specificity of binding, changes in hemagglutinin sequence of the recent viruses and the role of sialic acid in productive infection.ResultsViruses that agglutinate, or do not agglutinate, chicken red cells show identical binding to a Glycan Array of 264 oligosaccharides, binding exclusively to a subset of alpha2-6-sialylsaccharides. We identified an amino acid change in hemagglutinin that seemed to correlate with chicken red cell binding but when tested by mutagenesis there was no effect. Recombinant hemagglutinins expressed on Sf-9 cells bound chicken red cells but the released recombinant baculoviruses agglutinated only human red cells. Similarly, an isolate that does not agglutinate chicken red cells show hemadsorption of chicken red cells to infected MDCK cells. We suggest that binding of chicken red cells to cell surface hemagglutinin but not to virions is due to a more favorable hemagglutinin density on the cell surface. We investigated whether a virus specific for alpha2-6 sialyloligosaccharides shows differential entry into cells that have varying proportions of alpha2-6 and alpha2-3 sialic acids, including human A549 and HeLa cells with high levels of alpha2-6 sialic acid, and CHO cells that have only alpha2-3 sialic acid. We found that the virus enters all cell types tested and synthesizes viral nucleoprotein, localized in the nucleus, and hemagglutinin, transported to the cell surface, but infectious progeny viruses were released only from MDCK cells.ConclusionAgglutination of chicken red cells does not correlate with altered binding to any oligosaccharide on the Glycan Array, and may result from increased avidity due to density of hemagglutinin and not increased affinity. Absence of alpha2-6 sialic acid does not protect a cell from influenza infection and the presence of high levels of alpha2-6-sialic acids on a cell surface does not guarantee productive replication of a virus with alpha2-6 receptor specificity.

Dataset Information

Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations.

Publications

Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations.

Similar Datasets

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