Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test*

Tsalik, Ephraim L.; Henao, Ricardo; Montgomery, Jesse; Nawrocki, Jeff; Aydın, Mert; Lydon, Emily; Ko, Emily R; Petzold, Elizabeth; Nicholson, Bradly P.; Cairns, Charles B.; Glickman, Seth W.; Quackenbush, Eugenia; Kingsmore, Stephen F.; Jaehne, Anja Kathrin; Rivers, Emanuel P.; Langley, Raymond J.; Fowler, Vance G.; McClain, Micah T.; Crisp, Robert J.; Ginsburg, Geoffrey S.; Burke, Thomas W.; Hemmert, Andrew; Woods, Christopher W.

doi:10.1097/ccm.0000000000005085

Cited by 41 publications

(52 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is a growing interest in host response-based diagnostics, where most signatures focus on identifying the pathogen class (e.g., viral or bacterial) ( 55 ). Adding pathogen-specific host responses would augment the utility of such diagnostic approaches.…”

Section: Discussionmentioning

confidence: 99%

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood

et al. 2021

Self Cite

View full text Add to dashboard Cite

Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections highlighted the importance of interferon pathway activation. However, the magnitude of the responses varied between pathogens. We also identified virus-specific responses to influenza, enterovirus/rhinovirus, and dengue infections. Influenza-specific differentially expressed genes (DEG) revealed up-regulation of pathways related to viral defense and down-regulation of pathways related to T cell and neutrophil responses. Functional analysis of entero/rhinovirus-specific DEGs revealed up-regulation of pathways for neutrophil activation, negative regulation of immune response, and p38MAPK cascade and down-regulation of virus defenses and complement activation. Functional analysis of dengue-specific up-regulated DEGs showed enrichment of pathways for DNA replication and cell division whereas down-regulated DEGs were mainly associated with erythrocyte and myeloid cell homeostasis, reactive oxygen and peroxide metabolic processes. In conclusion, our study will contribute to a better understanding of molecular mechanisms to viral infections in humans and the identification of biomarkers to distinguish different types of viral infections.

show abstract

Section: Discussionmentioning

confidence: 99%

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline ( S1 Checklist ). This is a secondary analysis of the RADICAL study, focusing on subjects with microbiologically confirmed bacterial ARI, viral ARI, or non-infectious illness and who had samples available to support all biomarker testing [ 23 ]. The study protocol and analysis plan for this study were not pre-specified at the time the RADICAL study was designed and implemented.…”

Section: Methodsmentioning

confidence: 99%

“…Since there is no gold standard to define whether ARI is bacterial, viral, or non-infectious, panel adjudication served as the reference standard [ 18 , 23 , 25 , 26 ]. Adjudications were performed by specialists in emergency medicine, infectious diseases, pulmonary medicine, or hospital medicine based on chart reviews performed >28 days after enrollment, and before measuring procalcitonin, the protein panel, or the mRNA panel.…”

Section: Methodsmentioning

confidence: 99%

“…The composition and development of the mRNA panel measured in this study was previously described [ 21 ]. In brief, the gene signature test is composed of two unique host response signatures: a bacterial host response signature that assigns a probability of having a bacterial vs. non-bacterial etiology and a viral host response signature that assigns a probability of having a viral vs. non-viral etiology ( Fig 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, patients with non-infectious illness can also be distinguished using host gene expression [ 18 ]. We have previously adapted this signature onto the BioFire FilmArray System, which is a rapid, sample-to-answer platform measuring host gene expression [ 20 , 21 ]. Validated in a large cohort of patients with ARI, this gene expression test accurately discriminated patients with bacterial infection, viral infection, coinfection, or no infection [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A comparison of host response strategies to distinguish bacterial and viral infection

et al. 2021

Self Cite

View full text Add to dashboard Cite

Objectives Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). Methods In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene expression mRNA panel were measured in 286 subjects with ARI from four emergency departments. Multinomial logistic regression and leave-one-out cross validation were used to evaluate the protein and mRNA tests. Results The mRNA panel performed better than alternative strategies to identify bacterial infection: AUC 0.93 vs. 0.83 for the protein panel and 0.84 for procalcitonin (P<0.02 for each comparison). This corresponded to a sensitivity and specificity of 92% and 83% for the mRNA panel, 81% and 73% for the protein panel, and 68% and 87% for procalcitonin, respectively. A model utilizing all three strategies was the same as mRNA alone. For the diagnosis of viral infection, the AUC was 0.93 for mRNA and 0.84 for the protein panel (p<0.05). This corresponded to a sensitivity and specificity of 89% and 82% for the mRNA panel, and 85% and 62% for the protein panel, respectively. Conclusions A gene expression signature was the most accurate host response strategy for classifying subjects with bacterial, viral, or non-infectious ARI.

show abstract

Evaluation of a Multivalent Transcriptomic Metric for Diagnosing Surgical Sepsis and Estimating Mortality Among Critically Ill Patients

Brakenridge

Chen²,

Loftus

et al. 2022

JAMA Netw Open

View full text Add to dashboard Cite

Key Points Question Can a whole-blood RNA transcriptomic metric (IMX) obtained in the first 12 hours after intensive care unit (ICU) admission accurately measure the presence of bacterial infection and risk for sepsis mortality? Findings In this diagnostic and prognostic study including 200 patients with critical illness enrolled from a surgical ICU, the IMX transcriptomic metric was equivalent to or significantly better than the sequential organ failure assessment score and existing biomarkers (procalcitonin and interleukin 6 levels) for the diagnosis of acute infections and estimation of 30-day mortality. Meaning These findings suggest that a single, rapid-turnaround, multivalent transcriptomic test could supplant existing metrics in identifying bacterial infection and estimating clinical outcomes among critically ill surgical patients.

show abstract

Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test*

Cited by 41 publications

References 48 publications

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood

A comparison of host response strategies to distinguish bacterial and viral infection

Evaluation of a Multivalent Transcriptomic Metric for Diagnosing Surgical Sepsis and Estimating Mortality Among Critically Ill Patients

Contact Info

Product

Resources

About