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Preparing for the Next Influenza Season: Monitoring the Emergence and Spread of Antiviral Resistance.

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Title: Preparing for the Next Influenza Season: Monitoring the Emergence and Spread of Antiviral Resistance.
Authors: Oh, Djin-Ye, Milde, Jeanette, Ham, Youngsun, Calderón, Julia Patricia Ramos, Wedde, Marianne, Dürrwald, Ralf, Duwe, Susanne C
Source: Infection & Drug Resistance; Feb2023, Vol. 16, p949-959, 11p
Subject Terms: INFLUENZA viruses, COVID-19 pandemic, NUCLEOTIDE sequencing, ION channels, NEURAMINIDASE
Abstract: Purpose: The relaxation of pandemic restrictions in 2022 has led to a reemergence of respiratory virus circulation worldwide and anticipation of substantial influenza waves for the 2022/2023 Northern Hemisphere winter. Therefore, the antiviral susceptibility profiles of human influenza viruses circulating in Germany were characterized. Methods: Between October 2019 (week 40/2019) and March 2022 (week 12/2022), nasal swabs from untreated patients with acute respiratory symptoms were collected in the national German influenza surveillance system. A total of 598 influenza viruses were isolated and analyzed for susceptibility to oseltamivir, zanamivir and peramivir, using a neuraminidase (NA) inhibition assay. In addition, next-generation sequencing was applied to assess molecular markers of resistance to NA, cap-dependent endonuclease (PA) and M2 ion channel inhibitors (NAI, PAI, M2I) in 367 primary clinical samples. Furthermore, a genotyping assay based on RT-PCR and pyrosequencing to rapidly assess the molecular resistance marker PA-I38X in PA genes was designed and established. Results: While NAI resistance in the strict sense, defined by a ≥ 10-fold (influenza A) or ≥ 5-fold (influenza B) increase of NAI IC50, was not detected, a subtype A(H1N1)pdm09 isolate displayed 2.3- to 7.5-fold IC50 increase for all three NAI. This isolate carried the NA-S247N substitution, which is known to enhance NAI resistance induced by NA-H275Y. All sequenced influenza A viruses carried the M2-S31N substitution, which confers resistance to M2I. Of note, one A(H3N2) virus displayed the PA-I38M substitution, which is associated with reduced susceptibility to the PAI baloxavir marboxil. Pyrosequencing analysis confirmed these findings in the original clinical specimen and in cultured virus isolate, suggesting sufficient replicative fitness of this virus mutant. Conclusion: Over the last three influenza seasons, the vast majority of influenza viruses in this national-level sentinel were susceptible to NAIs and PAIs. These findings support the use of antivirals in the upcoming influenza season. [ABSTRACT FROM AUTHOR]
Copyright of Infection & Drug Resistance is the property of Dove Medical Press Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Preparing for the Next Influenza Season: Monitoring the Emergence and Spread of Antiviral Resistance.
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  Data: <searchLink fieldCode="AR" term="%22Oh%2C+Djin-Ye%22">Oh, Djin-Ye</searchLink><br /><searchLink fieldCode="AR" term="%22Milde%2C+Jeanette%22">Milde, Jeanette</searchLink><br /><searchLink fieldCode="AR" term="%22Ham%2C+Youngsun%22">Ham, Youngsun</searchLink><br /><searchLink fieldCode="AR" term="%22Calderón%2C+Julia+Patricia+Ramos%22">Calderón, Julia Patricia Ramos</searchLink><br /><searchLink fieldCode="AR" term="%22Wedde%2C+Marianne%22">Wedde, Marianne</searchLink><br /><searchLink fieldCode="AR" term="%22Dürrwald%2C+Ralf%22">Dürrwald, Ralf</searchLink><br /><searchLink fieldCode="AR" term="%22Duwe%2C+Susanne+C%22">Duwe, Susanne C</searchLink>
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  Data: Infection & Drug Resistance; Feb2023, Vol. 16, p949-959, 11p
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  Data: <searchLink fieldCode="DE" term="%22INFLUENZA+viruses%22">INFLUENZA viruses</searchLink><br /><searchLink fieldCode="DE" term="%22COVID-19+pandemic%22">COVID-19 pandemic</searchLink><br /><searchLink fieldCode="DE" term="%22NUCLEOTIDE+sequencing%22">NUCLEOTIDE sequencing</searchLink><br /><searchLink fieldCode="DE" term="%22ION+channels%22">ION channels</searchLink><br /><searchLink fieldCode="DE" term="%22NEURAMINIDASE%22">NEURAMINIDASE</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Purpose: The relaxation of pandemic restrictions in 2022 has led to a reemergence of respiratory virus circulation worldwide and anticipation of substantial influenza waves for the 2022/2023 Northern Hemisphere winter. Therefore, the antiviral susceptibility profiles of human influenza viruses circulating in Germany were characterized. Methods: Between October 2019 (week 40/2019) and March 2022 (week 12/2022), nasal swabs from untreated patients with acute respiratory symptoms were collected in the national German influenza surveillance system. A total of 598 influenza viruses were isolated and analyzed for susceptibility to oseltamivir, zanamivir and peramivir, using a neuraminidase (NA) inhibition assay. In addition, next-generation sequencing was applied to assess molecular markers of resistance to NA, cap-dependent endonuclease (PA) and M2 ion channel inhibitors (NAI, PAI, M2I) in 367 primary clinical samples. Furthermore, a genotyping assay based on RT-PCR and pyrosequencing to rapidly assess the molecular resistance marker PA-I38X in PA genes was designed and established. Results: While NAI resistance in the strict sense, defined by a ≥ 10-fold (influenza A) or ≥ 5-fold (influenza B) increase of NAI IC<subscript>50</subscript>, was not detected, a subtype A(H1N1)pdm09 isolate displayed 2.3- to 7.5-fold IC<subscript>50</subscript> increase for all three NAI. This isolate carried the NA-S247N substitution, which is known to enhance NAI resistance induced by NA-H275Y. All sequenced influenza A viruses carried the M2-S31N substitution, which confers resistance to M2I. Of note, one A(H3N2) virus displayed the PA-I38M substitution, which is associated with reduced susceptibility to the PAI baloxavir marboxil. Pyrosequencing analysis confirmed these findings in the original clinical specimen and in cultured virus isolate, suggesting sufficient replicative fitness of this virus mutant. Conclusion: Over the last three influenza seasons, the vast majority of influenza viruses in this national-level sentinel were susceptible to NAIs and PAIs. These findings support the use of antivirals in the upcoming influenza season. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Infection & Drug Resistance is the property of Dove Medical Press Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.2147/IDR.S389263
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        Text: English
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      – SubjectFull: INFLUENZA viruses
        Type: general
      – SubjectFull: COVID-19 pandemic
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      – SubjectFull: NUCLEOTIDE sequencing
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      – SubjectFull: ION channels
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      – SubjectFull: NEURAMINIDASE
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              Text: Feb2023
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              Y: 2023
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