Host response profiling reveals heterogenous immune responses in hospitalised adults with respiratory viral detection

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.