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Host immunity dictates influenza A(H1N1)pdm09 infection outcome in hematology–oncology patients

Bone Marrow Transplantation volume 51, pages 138–141 (2016)Cite this article

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Hematology–oncology patients can develop remarkably prolonged influenza virus excretion with an enigmatic wide clinical spectrum.1, 2, 3, 4, 5, 6 These patients often develop mild virus-associated symptoms and occasional bacterial or fungal pneumonic co-infections, but significant numbers of cases develop severe influenza virus-associated lower respiratory tract infection (LRTI) and acute respiratory distress syndrome (ARDS). Risk factors for influenza LRTI include profound lymphopenia, lack of early antiviral treatment and old age.5, 6 Pathogenesis of severe viral LRTI and ARDS is unclear and may include virus-induced pathology or excessive immunopathology.7 Impaired influenza-specific host immune responses are well-established in hematology–oncology patients but surprisingly little is known about the interactions with virus-associated clinical manifestations and outcomes. The recent introduction of influenza A (H1N1)pdm09 virus in the human population with limited preexistent immunity provided the opportunity to evaluate the role of innate and adaptive host immune findings in determining virus-specific symptoms and viral clearance among hematology–oncology patients with prolonged viral excretion.

In this observational study, adult hematology–oncology patients hospitalized with ⩾14 days prolonged A(H1N1)pdm09 virus excretion between November 2009 and April 2013 were eligible for inclusion. The institutional review board approved the pre-established study protocol and informed consent forms that were obtained from all subjects. Patients or legal representatives signed informed consent for voluntary study participation and confidentiality. Permission was granted for clinical data collection, blood draw of a research specimen and immunologic studies. Exclusion criteria were patients aged <18 years, patients deemed unfit by the treating physician (for example, owing to severe underlying bleeding disorders, religious background including Jehova’s witnesses, altered mental or emotional status) and patients or legal representatives not wishing to enter the study. Medical records were reviewed for relevant clinical findings, virus-associated symptoms and outcomes. Respiratory specimens were assessed for A(H1N1)pdm09, neuraminidase gene H275Y mutation encoding oseltamivir resistance and other respiratory viruses using real-time PCR and viral culture.8 Pulmonary imaging (chest radiography or computed tomography), bronchoalvolar lavage microbiology results and broad-spectrum antimicrobial treatment regimens were evaluated to confirm severe A(H1N1)pdm09-associated LRTI and ARDS requiring invasive mechanical ventilation and to exclude concomitant infections (viral, bacterial or fungal) and non-infectious cardiopulmonary causes (lung embolism, pneumothorax or congestive cardiac failure).

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Acknowledgements

We thank Eric Claas (Department of Medical Microbiology) and Geeske Brouwer-Mandema (Department of Hematology) for valuable assistance and advice. We are indebted to Martina Geelhoed-Mieras, Carel van Baalen and Tamara Roelofse (Department of Viroscience) for excellent technical support. None of these persons were financially compensated for providing assistance and technical support.

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Authors and Affiliations

  1. Departments of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands

    J Gooskens & A C M Kroes

  2. Departments of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    W A F Marijt

  3. Departments of Intensive Care, Leiden University Medical Center, Leiden, The Netherlands

    E H R van Essen

  4. Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands

    G F Rimmelzwaan

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  1. J Gooskens
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Corresponding author

Correspondence to J Gooskens.

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Competing interests

GFR reported his part-time employment as a consultant of Viroclinics Biosciences BV. The remaining authors declare no conflict of interest.

Additional information

International meeting at which all or part of the information has been presented: 17th International Symposium on Infections in the Immunocompromised Host, Genova, Italy, June 2012. 23rd European Congress of Clinical Microbiology and Infectious Diseases, Berlin, Germany, April 2013. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, USA, September 2015.

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Gooskens, J., Marijt, W., van Essen, E. et al. Host immunity dictates influenza A(H1N1)pdm09 infection outcome in hematology–oncology patients. Bone Marrow Transplant 51, 138–141 (2016). https://doi.org/10.1038/bmt.2015.214

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