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Biomarkers for Virus Discovery and Diagnosis

Gene expression patterns in nasal mucosa of subjects with and without respiratory symptoms (Cheemarla et al, The Lancet Microbe, 2023). (A) Heatmap showing nasopharyngeal transcriptome patterns in healthy subjects (black), patients with known respiratory virus infections(colors), and individuals with respiratory illness but no diagnosis (purple). (B, C) UMAP plots showing the relationship between transcriptomes of known virus-positive and virus-negative samples and those discovered using host response-based screening. Virus-positive samples are orange (SARS-CoV-2), green (CoV-NL63), and blue (rhinovirus); discovered samples are purple; and virus-negative samples are black. (C) UMAP plot indicating samples with moderate or high bacterial pathobiont (Haemophilus influenzae or Moraxella catarrhalis) concentrations. rpm=reads per million.

Standard diagnostic tests for viruses (e.g. PCR) are virus-specific, but the body's innate immune sensors can diagnose broad categories of infection with no prior knowledge of the pathogen. Eavesdropping on the body’s diagnosis has many potential uses, including reducing the cost and ease of screening for known respiratory viruses, and aiding detection and diagnosis of unexpected or emerging viruses.

In collaboration with the Yale Diagnostic Virology Laboratory, we defined biomarkers of the innate immune response to viral infection can serve as a pan-viral diagnostic tests, capturing infections with both known viruses and unexpected or emerging viruses.

Antiviral Response in the Nasopharynx Identifies Patients With Respiratory Virus Infection

We used this strategy to find undiagnosed respiratory viruses from patients undergoing standard testing, whose viruses were missed because they were not the “usual suspects” and were not tested for by the standard virus PCR panel. Discovered viruses included influenza C virus and four missed cases of SARS-CoV-2 from early in the COVID-19 pandemic.

Nasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study

We are currently pursuing applications of biomarker testing for basic research on human immunology and for clinical care and public health.

Predictive value of CXCL10 or CXCL11 protein level for detection of respiratory virus in 151 patient nasopharyngeal swabs (Landry and Foxman, 2018). A, Correlation between NP swab CXCL10 or CXCL11 protein level and detection of respiratory virus in nasopharyngeal swabs. Viruses not on the original test panel are shown in red, included 4 coronaviruses and parainfluenza virus 4. Horizontal bar in column labeled virus indicates detection of respiratory virus in the sample; asterisks indicate samples that tested positive for viruses not in the original test panel. B, Receiver operating characteristic (ROC) curves for CXCL10 (dashed line) and CXCL11 (solid line) concentrations as predictors of virus detection in this sample set. C, Viruses detected virus positive samples.