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In Progress
Clinical

- Study Type: Natural Infection

- Legends:

- MV group needed invasive mechanical ventilation following admission

- NMV group was composed of those patients not needing mechanical ventilation at any moment during hospitalization

Purpose

Critical disease caused by the new 2009 pandemic influenza virus (nvH1N1) is a challenge for physicians and scientist. As evidenced in SARS and H5N1, the development of an effective immune response plays a key role to overcome viral diseases. We studied host`s gene expression signatures, cytokine and antibody responses along the first week of hospitalization in 19 critically ill patients with primary nvH1N1 pneumonia and two degrees of respiratory involvement. Presence of comorbidities and absence of immunosuppresory conditions were the common antecedents in both groups. The most severe patients (n=12) showed persistant respiratory viral secretion, increased levels of pro-inflammatory cytokines and chemokines in serum, and elevated systemic levels of two immunosuppresory cytokines (IL-10 and IL-1ra). Both groups were able to produce specific antibodies against the virus. The average day for antibody production was day 9 in the course of the disease, defining an early period of innate immunity and a late period of adaptive immunity. The most severe group evidenced a poor expression of a set of MHC class II and T cell receptor (TCR) related genes participating in antigen presentation and cell mediated immune responses in the late phase. 7 patients of this group finally died. This findings evidence that, as observed in sepsis, severe H1N1 disease course with immunoparalysis, which could explain the poor control of the virus along with the increased incidence of bacterial superinfection observed in these patients.

Hypothesis

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Experimental Design

19 patients attending to the participants ICUs with primary viral pneumonia during the acute phase of influenza virus illness with acute respiratory distress and unequivocal alveolar opacification involving two or more lobes with negative respiratory and blood bacterial cultures at admission were recruited from November the 1st to December the 31st 2009. Serial blood samples for plasma, serum and RNA were collected by using Serum, EDTA and PaxGene (BD®) venous blood vacuum collection following manufacturer instructions at day 1, 3/5 and 7 according to an unified protocol for all the participant ICUs. A pharyngeal sample was collected in paralel. RNA from blood was processed for gene expression analysis by using Sentrix Human-6 v2 Expression BeadChips (Illumina, San Diego, CA). RNA from blood obtained from 4 healthy controls was used for comparison purposes. Samples were distributed in four groups depending on whether or not the patients nedeed of mechanical ventilation, and on the early/late phase of the disease (before or after day 9 respectively).

Experimental Variables

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Controls

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Methods

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Additional Information

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Microarray
Illumina HumanWG-6 v2
40 Samples Loaded: 40
Human (Homo sapiens)
Whole Blood
H1N1
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title tissue group patient Disease phase
GSM542941 Healthy Control, biological rep1 Blood Control control control
GSM542942 Healthy Control, biological rep2 Blood Control control control
GSM542943 Healthy Control, biological rep3 Blood Control control control
GSM542944 Healthy Control, biological rep4 Blood Control control control
GSM542945 Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep1 Blood H1N1 NMV late period 1 late period
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Sample Set Spreadsheet
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Sample Set Spreadsheet
sampleset4000028_sampleannotations_Group.csv
Sample Set Spreadsheet
sampleset4000028_sampleannotations_Group.csv
Sample Set Spreadsheet
Raw Signal
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Sample ID !Sample Title Tissue Group Patient Disease phase Mechanical ventilation Virus strain
GSM542941
Healthy Control, biological rep1
Blood
Control
control
control
 
none
GSM542942
Healthy Control, biological rep2
Blood
Control
control
control
 
none
GSM542943
Healthy Control, biological rep3
Blood
Control
control
control
 
none
GSM542944
Healthy Control, biological rep4
Blood
Control
control
control
 
none
GSM542945
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep1
Blood
H1N1 NMV late period
1
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542946
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep2
Blood
H1N1 NMV late period
1
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542947
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep3
Blood
H1N1 NMV late period
1
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542948
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep1
Blood
H1N1 MV early period
2
early period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542949
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep2
Blood
H1N1 MV early period
2
early period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542950
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep1
Blood
H1N1 NMV early period
3
early period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542951
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep4
Blood
H1N1 NMV late period
4
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542952
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep3
Blood
H1N1 MV early period
5
early period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542953
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep1
Blood
H1N1 MV late period
5
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542954
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep5
Blood
H1N1 NMV late period
6
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542955
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep2
Blood
H1N1 MV late period
7
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542956
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep3
Blood
H1N1 MV late period
8
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542957
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep2
Blood
H1N1 NMV early period
4
early period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542958
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep4
Blood
H1N1 MV early period
9
early period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542959
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep4
Blood
H1N1 MV late period
10
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542960
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep5
Blood
H1N1 MV late period
7
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542961
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep6
Blood
H1N1 NMV late period
4
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542962
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep6
Blood
H1N1 MV late period
10
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542963
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep5
Blood
H1N1 MV early period
5
early period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542964
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep3
Blood
H1N1 NMV early period
6
early period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542965
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep7
Blood
H1N1 MV late period
7
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542966
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep8
Blood
H1N1 MV late period
8
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542967
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep9
Blood
H1N1 MV late period
11
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542968
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep7
Blood
H1N1 NMV late period
4
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542969
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep10
Blood
H1N1 MV late period
12
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542970
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep4
Blood
H1N1 NMV early period
13
early period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542971
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep8
Blood
H1N1 NMV late period
13
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542972
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep5
Blood
H1N1 NMV early period
14
early period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542973
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period, biological rep9
Blood
H1N1 NMV late period
14
late period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542974
Pandemic H1N1 positive critical patient under mechanical ventilation, early period, biological rep6
Blood
H1N1 MV early period
15
early period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542975
Pandemic H1N1 positive critical patient with no mechanical ventilation, early period, biological rep6
Blood
H1N1 NMV early period
16
early period
no
Pandemic influenza (A/H1N1 new subtype)
GSM542976
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep11
Blood
H1N1 MV late period
17
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542977
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep12
Blood
H1N1 MV late period
17
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542978
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep13
Blood
H1N1 MV late period
18
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542979
Pandemic H1N1 positive critical patient under mechanical ventilation, late period, biological rep14
Blood
H1N1 MV late period
19
late period
yes
Pandemic influenza (A/H1N1 new subtype)
GSM542980
Pandemic H1N1 positive critical patient with no mechanical ventilation, late period,biological rep10
Blood
H1N1 NMV late period
16
late period
no
Pandemic influenza (A/H1N1 new subtype)

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