Article: Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection

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TitleDelayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection
AuthorsTo, KKW
Hung, IFN
Li, IWS
Lee, KL
Koo, CK
Yan, WW
Liu, R
Ho, KY
Chu, KH
Watt, CL
Luk, WK
Lai, KY
Chow, FL
Mok, T
Buckley, T
Chan, JFW
Wong, SSY
Zheng, B
Chen, H
Lau, CCY
Tse, H
Cheng, VCC
Chan, KH
Yuen, KY
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://www.oxfordjournals.org/our_journals/cid/
CitationClinical Infectious Diseases, 2010, v. 50 n. 6, p. 850-859 [How to Cite?]
DOI: http://dx.doi.org/10.1086/650581
AbstractBackground: Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods: We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-withoutARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results: Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions: The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death. © 2010 by the Infectious Diseases Society of America. All rights reserved.
ISSN1058-4838
2011 Impact Factor: 9.154
2011 SCImago Journal Rankings: 0.821
DOIhttp://dx.doi.org/10.1086/650581
ISI Accession Number IDWOS:000274656000009
Funding AgencyGrant Number
Providence Foundation Limited
University Grant Council
Research Fund for the Control of Infectious Diseases (RFCID)
Food and Health Bureau of the Hong Kong SAR Government
Funding Information:

The Providence Foundation Limited in memory of the late Dr Lui Hac Minh, the University Grant Council, and the Research Fund for the Control of Infectious Diseases (RFCID) of the Food and Health Bureau of the Hong Kong SAR Government.

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorTo, KKW
dc.contributor.authorHung, IFN
dc.contributor.authorLi, IWS
dc.contributor.authorLee, KL
dc.contributor.authorKoo, CK
dc.contributor.authorYan, WW
dc.contributor.authorLiu, R
dc.contributor.authorHo, KY
dc.contributor.authorChu, KH
dc.contributor.authorWatt, CL
dc.contributor.authorLuk, WK
dc.contributor.authorLai, KY
dc.contributor.authorChow, FL
dc.contributor.authorMok, T
dc.contributor.authorBuckley, T
dc.contributor.authorChan, JFW
dc.contributor.authorWong, SSY
dc.contributor.authorZheng, B
dc.contributor.authorChen, H
dc.contributor.authorLau, CCY
dc.contributor.authorTse, H
dc.contributor.authorCheng, VCC
dc.contributor.authorChan, KH
dc.contributor.authorYuen, KY
dc.date.accessioned2010-10-31T11:09:59Z
dc.date.available2010-10-31T11:09:59Z
dc.date.issued2010
dc.description.abstractBackground: Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods: We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-withoutARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results: Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions: The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death. © 2010 by the Infectious Diseases Society of America. All rights reserved.
dc.description.naturepublished_or_final_version
dc.identifier.citationClinical Infectious Diseases, 2010, v. 50 n. 6, p. 850-859 [How to Cite?]
DOI: http://dx.doi.org/10.1086/650581
dc.identifier.citeulike6649981
dc.identifier.doihttp://dx.doi.org/10.1086/650581
dc.identifier.epage859
dc.identifier.hkuros173891
dc.identifier.isiWOS:000274656000009
Funding AgencyGrant Number
Providence Foundation Limited
University Grant Council
Research Fund for the Control of Infectious Diseases (RFCID)
Food and Health Bureau of the Hong Kong SAR Government
Funding Information:

The Providence Foundation Limited in memory of the late Dr Lui Hac Minh, the University Grant Council, and the Research Fund for the Control of Infectious Diseases (RFCID) of the Food and Health Bureau of the Hong Kong SAR Government.

dc.identifier.issn1058-4838
2011 Impact Factor: 9.154
2011 SCImago Journal Rankings: 0.821
dc.identifier.issue6
dc.identifier.openurl
dc.identifier.pmid20136415
dc.identifier.scopuseid_2-s2.0-77749282915
dc.identifier.spage850
dc.identifier.urihttp://hdl.handle.net/10722/125075
dc.identifier.volume50
dc.languageeng
dc.publisherOxford University Press. The Journal's web site is located at http://www.oxfordjournals.org/our_journals/cid/
dc.publisher.placeUnited States
dc.relation.ispartofClinical Infectious Diseases
dc.relation.referencesReferences in Scopus
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.subject.meshCohort Studies
dc.subject.meshCytokines - blood
dc.subject.meshInfluenza A Virus, H1N1 Subtype - isolation and purification
dc.subject.meshInfluenza, Human - immunology - pathology - virology
dc.subject.meshViral Load
dc.titleDelayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection
dc.typeArticle
Author Affiliations
  1. Kwong Wah Hospital
  2. Tseung Kwan O Hospital
  3. Yan Chai Hospital - Hong Kong
  4. Tuen Mun Hospital
  5. The University of Hong Kong
  6. Princess Margaret Hospital Hong Kong
  7. Queen Elizabeth Hospital Hong Kong
  8. Pamela Youde Nethersole Eastern Hospital
  9. United Christian Hospital Hong Kong
  10. Ruttonjee Hospital and Tang Shiu Kin Hospitals
  11. Kowloon Hospital
  12. Caritas Medical Centre Hong Kong