Host Gene Expression Tests Accurately Identify Bacterial vs Viral Respiratory Infections

Illustration of human lungs with infection
Researchers assessed the ability of rapid host gene expression testing to distinguish between acute respiratory infections of viral vs bacterial origin.

Among patients with an acute respiratory infection (ARI), host response bacterial/viral (HR-B/V) testing accurately identified infections of bacterial vs viral origin and was superior to the use of procalcitonin measurements, according to results of a study published in JAMA Network Open.

Researchers conducted a prospective multicenter study to assess the performance of the HR-B/V test, a rapid host gene expression-based test with the ability to quantify the expression of 45 host messenger RNA targets and determine the probability of bacterial infection. This study was conducted between October 2014 and December 2020 at 10 US emergency departments and included children and adults who were diagnosed with febrile ARI within the past 7 days. Patients without a clinically adjudicated bacterial or viral infection were excluded.

Among a total of 616 patients, the median age was 24 years (IQR, 14-49), 52.6% were men, and the median procalcitonin concentration was 0.05 (IQR, 0-0.13) and 0.12 (IQR, 0-0.47) ng/mL among those with viral and bacterial infections, respectively (P =.004).

The primary analysis comprised 334 patients with microbiologically-confirmed infection. The researchers found that HR-B/V testing identified bacterial infections among this patient cohort with a sensitivity of 89.8%, a specificity of 82.1%, and a negative predictive value (NPV) of 97.9%. Compared with HR-B/V testing, distinguishing bacterial infections from viral via procalcitonin measurements (0.25 ng/mL) had increased specificity (87.0%), but decreased sensitivity (28.6%) and NPV (87.6%). In addition, the area under the receiver operating characteristic curve (AUROC) score was increased for HR-B/V testing (0.92; 95% CI, 0.87-0.94) vs procalcitonin measurements (0.59; 95% CI, 0.49-0.68).

A secondary analysis was performed among the entire patient cohort, including those with discordant clinical adjudications or a lack of microbiologically-confirmed infection. Results of HR-B/V testing were similar among this cohort compared with those included in the primary analysis. Analysis of HR-B/V testing vs procalcitonin measurements showed that HR-B/V tests had increased sensitivity (86.4% vs 31.6%), decreased specificity (71.9% vs 87.3%), and increased NPV (95.7% vs 84.5%). In addition, AUROC scores also were increased for HR-B/V testing among this patient cohort (0.85; 95% CI, 0.81-0.89 vs 0.62; 95% CI, 0.56-0.67).

Study limitations included the use of clinical adjudication as a reference standard, the lack of analytical validations such as site-to-site or run-to-run variability, and the lack of patients with nonrespiratory infections.

According to the researchers, “[these] 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.”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Ko ER, Henao R, Frankey K, et al. Prospective validation of a rapid host gene expression test to discriminate bacterial from viral respiratory infection. JAMA Netw Open. 2022;5(4):e227299. doi:10.1001/jamanetworkopen.2022.7299