Dataset Information

Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.

ABSTRACT: To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.

SUBMITTER: Zhai Y

PROVIDER: S-EPMC4466531 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.

Zhai Yijie Y Franco Luis M LM Atmar Robert L RL Quarles John M JM Arden Nancy N Bucasas Kristine L KL Wells Janet M JM Niño Diane D Wang Xueqing X Zapata Gladys E GE Shaw Chad A CA Belmont John W JW Couch Robert B RB

PLoS pathogens 20150612 6

To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression ...[more]

PMID: 26070066

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Project description:The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells and uncover the complex dynamics of host response to ARIs such as pandemic H1N1. To understand the molecular bases and network orchestration of host responses, we prospectively enrolled 1610 healthy adults in the fall of 2009 and 2010, followed the subjects with influenza-like illness (N=133) for 3 weeks, and examined changes in their peripheral blood gene expression. We discovered distinct phases of the host response spanning 6 days after infection, and identified genes that differentiate influenza from non-influenza virus infection. We examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. Healthy adults were invited to enroll to be followed for acute respiratory illness (ARI) through two consecutive influenza seasons 2009-2010 and 2010-2011. After subjects provided consent, baseline blood specimens were obtained during enrollment. Subjects were given thermometers and instructions to call and report for evaluation within 48 hours of ARI onset. Those persons who had a new ARI were seen within 48 hours of onset (day 0) and 2, 4, and 6 days later for repeat evaluation, blood specimen collections, and medical care (including the antiviral zanamivir if indicated) and 21 days later for collection of convalescent specimens. Nasal wash samples were collected for virus detection by RT-PCR on day 0 and day 2. Surveillance for influenza was terminated after 5.5 months; all subjects were asked to return for specimen collection and to provide a medical and ARI history in spring of next year. Serum specimens obtained at baseline, day 0 and day 21 visits for illnesses, and the terminal visit were tested simultaneously using hemagglutination-inhibition (HAI) antibody assay for Influenza H1N1, H3N2, and Influenza B strains. Peripheral blood RNA (PaxGene) obtained from blood specimens at each visit were analyzed using Illumina Human HT-12 v4. The study was repeated 2010-2011. A total of 880 arrays, corresponding to 133 individuals, passed quality control and are included in this data set.

Project description:Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity.DesignProspective cohort study.SettingMulticenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States.PatientsPatients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics.InterventionsNone.Measurements and main resultsMeasurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes.ConclusionsSARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI.

Dataset Information

Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.

Publications

Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections--A Prospective Cohort Study.

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