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Assessing Respiratory Immune Responses to Haemophilus Influenzae
Published on: June 29, 2021
Host response profiling reveals heterogenous immune responses in hospitalised adults with respiratory viral detection
Alex R Tanner1, Bilge Eylem Dedeoglu1, Nathan J Brendish2
1NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Background:
Acute Respiratory Infection (ARI) is the commonest reason for antibiotic use. Distinguishing bacterial from viral ARI is challenging, leading to antibiotic overuse and antimicrobial resistance. Respiratory viruses detected by PCR in patients with ARI may be causally related, but asymptomatic detection and bacterial co-infection can also occur. Host response profiling may therefore provide insights into the clinical significance of viral detection.
Methods:
PAXgene RNA blood samples from patients hospitalised with ARI were tested using the TriVerity test (Inflammatix, Sunnyvale, CA, USA). This host response test measures levels of 29 specific mRNAs to generate separate scores from 1 to 50 indicating the likelihood of bacterial and viral infection (1-10 very low, 11-20 low, 21-30 moderate, 31-40 high, 41-50 very high). Clinical and laboratory data were collected and all patients had PCR testing for respiratory viruses. Scores were compared in patients with and without viral detection and according to virus type. For patient with rhino enterovirus (RhV) detected, scores were compared according to clinical diagnosis.
Findings:
169 patients were tested. Median age was 60 (45-74) years, 152 (90%) received antibiotics, and 103 (61%) patients had viruses detected. Median TriVerity viral scores were highest for influenza (44), lowest for RhV (27), and intermediate for other viruses. Evaluating individual virus-infected patients, there was marked heterogeneity in both viral and bacterial scores between patients testing positive for the same viral pathogen. This was most marked for RhV (IQR 15-37). Viral scores for RhV positive patients were higher in patients with a discharge diagnosis of asthma exacerbation, 35 (31-42) compared to exacerbation of COPD, 16 (11-28) and pneumonia, 18 (11-36; p=0·0095) and bacterial scores followed the opposite pattern.
Interpretation:
Host gene expression scores suggest that the true aetiology of ARI in adults with respiratory viruses detected by PCR is heterogenous, especially for RhV, and that careful interpretation is required before attributing causality. Combining pathogen PCR with host response testing may aid interpretation and could reduce unnecessary antibiotic use.
Insights
Distinguishing viral from bacterial acute respiratory infections (ARI) is difficult, leading to antibiotic overuse. Host gene expression profiling shows varied causes for ARI, even with detected viruses, aiding interpretation and potentially reducing antibiotic prescriptions.
Area of Science:
- Infectious Diseases
- Molecular Diagnostics
- Host-Pathogen Interactions
Background:
- Acute Respiratory Infection (ARI) is a primary driver of antibiotic use.
- Differentiating viral from bacterial ARI is challenging, contributing to antimicrobial resistance.
- Host response profiling offers insights into the clinical significance of detected respiratory viruses.
Purpose of the Study:
- To evaluate host gene expression profiling for differentiating ARI etiology.
- To assess the clinical significance of viral detection in ARI patients.
- To explore the utility of host response testing in guiding antibiotic use.
Main Methods:
- PAXgene RNA blood samples from hospitalized ARI patients were analyzed using the TriVerity host response test.
- The test measures 29 mRNAs to generate bacterial and viral infection likelihood scores.
- Results were compared between patients with and without viral detection, and by virus type, including rhinoenterovirus (RhV).
Main Results:
- 169 patients were tested; 61% had detected viruses.
- Viral scores varied by virus type, highest for influenza and lowest for RhV.
- Significant heterogeneity in host response scores was observed among patients with the same viral pathogen, particularly for RhV.
- RhV-positive patients with asthma exacerbation showed higher viral scores than those with COPD exacerbation or pneumonia.
Conclusions:
- Host gene expression profiling reveals heterogeneous etiologies in adult ARI patients with detected viruses, especially RhV.
- Careful interpretation of viral detection is needed to attribute causality.
- Combining PCR with host response testing may improve ARI diagnosis and reduce unnecessary antibiotic use.
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