Dataset Information

Host Gene Expression in Nose and Blood for the Diagnosis of Viral Respiratory Infection.

ABSTRACT: BACKGROUND:Recently there has been a growing interest in the potential for host transcriptomic analysis to augment the diagnosis of infectious diseases. METHODS:We compared nasal and blood samples for evaluation of the host transcriptomic response in children with acute respiratory syncytial virus (RSV) infection, symptomatic non-RSV respiratory virus infection, asymptomatic rhinovirus infection, and virus-negative asymptomatic controls. We used nested leave-one-pair-out cross-validation and supervised principal components analysis to define small sets of genes whose expression patterns accurately classified subjects. We validated gene classification scores using an external data set. RESULTS:Despite lower quality of nasal RNA, the number of genes detected by microarray in each sample type was equivalent. Nasal gene expression signal derived mainly from epithelial cells but also included a variable leukocyte contribution. The number of genes with increased expression in virus-infected children was comparable in nasal and blood samples, while nasal samples also had decreased expression of many genes associated with ciliary function and assembly. Nasal gene expression signatures were as good or better for discriminating between symptomatic, asymptomatic, and uninfected children. CONCLSUSIONS:Our results support the use of nasal samples to augment pathogen-based tests to diagnose viral respiratory infection.

SUBMITTER: Yu J

PROVIDER: S-EPMC6420164 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Host Gene Expression in Nose and Blood for the Diagnosis of Viral Respiratory Infection.

Yu Jinsheng J Peterson Derick R DR Baran Andrea M AM Bhattacharya Soumyaroop S Wylie Todd N TN Falsey Ann R AR Mariani Thomas J TJ Storch Gregory A GA

The Journal of infectious diseases 20190401 7

<h4>Background</h4>Recently there has been a growing interest in the potential for host transcriptomic analysis to augment the diagnosis of infectious diseases.<h4>Methods</h4>We compared nasal and blood samples for evaluation of the host transcriptomic response in children with acute respiratory syncytial virus (RSV) infection, symptomatic non-RSV respiratory virus infection, asymptomatic rhinovirus infection, and virus-negative asymptomatic controls. We used nested leave-one-pair-out cross-val ...[more]

PMID: 30339221

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Project description:BackgroundEarly and accurate identification of individuals with viral infections is crucial for clinical management and public health interventions. We aimed to assess the ability of transcriptomic biomarkers to identify naturally acquired respiratory viral infection before typical symptoms are present.MethodsIn this index-cluster study, we prospectively recruited a cohort of undergraduate students (aged 18-25 years) at Duke University (Durham, NC, USA) over a period of 5 academic years. To identify index cases, we monitored students for the entire academic year, for the presence and severity of eight symptoms of respiratory tract infection using a daily web-based survey, with symptoms rated on a scale of 0-4. Index cases were defined as individuals who reported a 6-point increase in cumulative daily symptom score. Suspected index cases were visited by study staff to confirm the presence of reported symptoms of illness and to collect biospecimen samples. We then identified clusters of close contacts of index cases (ie, individuals who lived in close proximity to index cases, close friends, and partners) who were presumed to be at increased risk of developing symptomatic respiratory tract infection while under observation. We monitored each close contact for 5 days for symptoms and viral shedding and measured transcriptomic responses at each timepoint each day using a blood-based 36-gene RT-PCR assay.FindingsBetween Sept 1, 2009, and April 10, 2015, we enrolled 1465 participants. Of 264 index cases with respiratory tract infection symptoms, 150 (57%) had a viral cause confirmed by RT-PCR. Of their 555 close contacts, 106 (19%) developed symptomatic respiratory tract infection with a proven viral cause during the observation window, of whom 60 (57%) had the same virus as their associated index case. Nine viruses were detected in total. The transcriptomic assay accurately predicted viral infection at the time of maximum symptom severity (mean area under the receiver operating characteristic curve [AUROC] 0·94 [95% CI 0·92-0·96]), as well as at 1 day (0·87 [95% CI 0·84-0·90]), 2 days (0·85 [0·82-0·88]), and 3 days (0·74 [0·71-0·77]) before peak illness, when symptoms were minimal or absent and 22 (62%) of 35 individuals, 25 (69%) of 36 individuals, and 24 (82%) of 29 individuals, respectively, had no detectable viral shedding.InterpretationTranscriptional biomarkers accurately predict and diagnose infection across diverse viral causes and stages of disease and thus might prove useful for guiding the administration of early effective therapy, quarantine decisions, and other clinical and public health interventions in the setting of endemic and pandemic infectious diseases.FundingUS Defense Advanced Research Projects Agency.

Project description:ImportanceBacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship.ObjectiveTo validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI.Design, setting, and participantsThis prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days' duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc.InterventionsThe HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection.Main outcomes and measuresPerformance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score <0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score >0.73]) and compared with procalcitonin measurement.ResultsAmong 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P < .001), the specificity was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%; P < .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9% (95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants (90.9%) with acute COVID-19 as having a viral infection.Conclusions and relevanceIn this study, the HR-B/V test accurately discriminated bacterial from viral infection among patients with febrile ARI and was superior to procalcitonin measurement. The findings suggest that an accurate point-of-need host response test with high NPV may offer an opportunity to improve antibiotic stewardship and patient outcomes.

Dataset Information

Host Gene Expression in Nose and Blood for the Diagnosis of Viral Respiratory Infection.

Publications

Host Gene Expression in Nose and Blood for the Diagnosis of Viral Respiratory Infection.

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