Clinical management and viral genomic diversity analysis of a child's influenza A(H1N1)pdm09 infection in the context of a severe combined immunodeficiency

Antiviral Res. 2018 Dec;160:1-9. doi: 10.1016/j.antiviral.2018.10.009. Epub 2018 Oct 11.

Abstract

Introduction: A child with severe combined immunodeficiency (SCID) had an influenza A(H1N1)pdm09 infection with viral excretion longer than 6 months, during 2013-2014 influenza season, despite cord blood transplantation and antiviral treatments.

Methods: Conventional real-time RT-PCR methods were used to estimate viral load and to detect the presence of the common N1 neuraminidase (NA) H275Y substitution responsible for oseltamivir resistance. Next-generation sequencing (NGS) of influenza viruses was performed retrospectively to characterize viral quasispecies in specimens.

Results: The patient was first treated with oral oseltamivir, leading to detection of low-levels of NA-H275Y substitution. Concomitant cord blood cell transplantation, intravenous administration of zanamivir and immunoglobulins led to an increase in white blood cells and influenza viral load decrease. A viral rebound occurred as soon as the antiviral treatment was discontinued. Eventually, influenza viral load was negated with immune reconstitution. NGS found influenza quasispecies harboring NA-E119A substitution (10.3%). Moreover, NGS showed that viral genomic diversity evolved under antiviral treatment and immune status.

Conclusions: Conventional virological techniques were sufficient for influenza infection follow-up but NGS performances allowed characterization of viral variants evolution in this specific case of prolonged influenza virus infection. New and efficient treatments against influenza in immunocompromised patients are needed.

Keywords: Influenza A(H1N1)pdm09 virus; Intravenous zanamivir; NA-E119A substitution; NA-H275Y substitution; Next-generation sequencing; Oseltamivir resistance.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology
  • Child
  • Cord Blood Stem Cell Transplantation
  • Drug Resistance, Viral
  • Genetic Variation*
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Influenza A Virus, H1N1 Subtype / classification
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / isolation & purification*
  • Influenza, Human / drug therapy
  • Influenza, Human / pathology*
  • Influenza, Human / virology*
  • Mutation, Missense
  • Neuraminidase / genetics
  • Oseltamivir / administration & dosage
  • Oseltamivir / pharmacology
  • Real-Time Polymerase Chain Reaction
  • Severe Combined Immunodeficiency / complications*
  • Viral Load
  • Viral Proteins / genetics
  • Zanamivir / administration & dosage

Substances

  • Antiviral Agents
  • Immunoglobulins, Intravenous
  • Viral Proteins
  • Oseltamivir
  • NA protein, influenza A virus
  • Neuraminidase
  • Zanamivir