1791. Novel Metabolomics Approach for the Diagnosis of Respiratory Viruses Directly from Nasopharyngeal Specimens

BACKGROUND: Respiratory virus infections are important causes of morbidity and mortality among pediatric and adult patients. These viruses infect respiratory epithelial cells, where they may induce specific metabolite alterations. As a proof-of-concept, we investigate the novel use of liquid chromatography (LC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF) for the study of host cell metabolite alterations to diagnose and differentiate respiratory viruses. METHODS: We studied nasopharyngeal swab samples positive for respiratory viruses by the eSensor Respiratory Viral Panel (GenMark Diagnostics, Carlsbad, CA). Banked, frozen samples (−80°C) stored in viral transport media were retrieved and thawed. Aliquots of 100 μL were centrifuged at 13.3 × g for 15 minutes, and the filtrate was analyzed by Agilent 6545 Quadrupole LC/Q-TOF (Agilent Technologies, Santa Clara, CA). Compounds were separated using a novel column arrangement based on hydrophobicity and charge using a quaternary solvent manager, followed by accurate mass analysis by LC/Q-TOF. Agilent Mass Profiler 3D principal component analysis was performed, and compound identification was completed using the METLIN metabolite database. RESULTS: A total of 235 specimens were tested by LC/Q-TOF, including 195 positive specimens [including adenovirus, coronavirus, influenza A H1N1 and H3N2, influenza B, human metapneumovirus, parainfluenza viruses 1, 2, 3, and 4, respiratory syncytial virus (RSV), and rhinovirus] as well as 40 negative clinical specimens. LC/Q-TOF primary component analysis (PCA) allowed preliminary identification of key metabolites that distinguished all virus-positive specimens compared with the negative group, and differentiated respiratory viruses from one another including between influenza A 2009 H1N1 and H3N2 subtypes (Figure 1). CONCLUSION: Preliminary data from our LC/Q-TOF analysis show that respiratory viruses exhibit different host cell metabolomic profiles that allow viral differentiation to the species level, and for influenza A virus, the subtype level. This metabolomic approach has substantial potential for diagnostic applications in infectious diseases directly from patient samples, and may be eventually adapted for point-of-care testing. [Image: see text] DISCLOSURES: All authors: No reported disclosures.