title: Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia.
abstract: BACKGROUND
  Little is known about the virological and inflammatory responses of severe pandemic 2009 influenza A(H1N1) virus pneumonia during antiviral treatment.
  
  
  METHODS
  In a prospective observational study, we recruited consecutive adults hospitalized with confirmed pandemic 2009 H1N1 infection during a 16-week period. Nasopharyngeal aspirate and non-respiratory samples (blood, stool and urine) were collected at presentation, and serial nasopharyngeal flocked swabs (NPFS) and tracheal aspirates (TA) were collected after initiating oseltamivir treatment for quantitative viral RNA assay, using real-time reverse transcriptase-PCR. Serial plasma samples were collected for cytokine/chemokine assay using cytometric bead array. Patients with severe pneumonia (lung infiltrates and hypoxaemia) were compared to those with milder illnesses.
  
  
  RESULTS
  A total of 66 patients were studied (mean age 43 ±20 years); 28 (42%) developed severe pneumonia, of whom 10 (15%) required intubation. Severe pneumonia was associated with older age, dyspnoea, delayed presentation >2 days from onset, extrapulmonary virus detection (13-28%) and higher viral concentration despite late-presentation (multiple linear regression, β=0.94, 95% confidence interval 0.15-1.74; P=0.02). Patients with severe pneumonia exhibited slow viral clearance with oseltamivir treatment, particularly in the lower respiratory tract (median [interquartile range] durations of RNA positivity after antiviral initiation were NPFS 6.0 days [3.0-8.0], TA 11.0 days [7.8-14.3] versus milder illness group NPFS of 2.0 days [1.0-3.0] days; P<0.01). High viral load in lower respiratory tract despite upper-tract RNA negativity and viral rebound after stopping treatment were noted in some patients. H275Y mutation was absent. High plasma levels of interleukin (IL)-6, CXCL-8 (IL-8), CCL2 (monocyte chemoattractant protein-1) and soluble tumour necrosis factor receptor-1 were observed, which correlated with the extent and progression of pneumonia in hospital.
  
  
  CONCLUSIONS
  In severe 2009 H1N1 pneumonia, viral clearance is slow with treatment, particularly in the lower respiratory tract. A more sustained antiviral regime appears warranted.
authors: Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China.
authors: Nelson
authors: N
authors: Lee
authors: Paul K S
authors: PK
authors: Chan
authors: Chun Kwok
authors: CK
authors: Wong
authors: Ka-Tak
authors: KT
authors: Wong
authors: Kin-Wing
authors: KW
authors: Choi
authors: Gavin M
authors: GM
authors: Joynt
authors: Philip
authors: P
authors: Lam
authors: Martin C W
authors: MC
authors: Chan
authors: Bonnie C K
authors: BC
authors: Wong
authors: Grace C Y
authors: GC
authors: Lui
authors: Winnie W Y
authors: WW
authors: Sin
authors: Rity Y K
authors: RY
authors: Wong
authors: Wai-Yip
authors: WY
authors: Lam
authors: Apple C M
authors: AC
authors: Yeung
authors: Ting-Fan
authors: TF
authors: Leung
authors: Hing-Yu
authors: HY
authors: So
authors: Alex W Y
authors: AW
authors: Yu
authors: Joseph J Y
authors: JJ
authors: Sung
authors: David S C
authors: DS
authors: Hui
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000821:virology; D058873:Pandemics; D011024:Pneumonia, Viral / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D012720:Severity of Illness Index; D014132:Trachea / Q000821:virology; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D012367:RNA, Viral