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In Science advances

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 85.1-86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis.

Ng Dianna L, Granados Andrea C, Santos Yale A, Servellita Venice, Goldgof Gregory M, Meydan Cem, Sotomayor-Gonzalez Alicia, Levine Andrew G, Balcerek Joanna, Han Lucy M, Akagi Naomi, Truong Kent, Neumann Neil M, Nguyen David N, Bapat Sagar P, Cheng Jing, Martin Claudia Sanchez-San, Federman Scot, Foox Jonathan, Gopez Allan, Li Tony, Chan Ray, Chu Cynthia S, Wabl Chiara A, Gliwa Amelia S, Reyes Kevin, Pan Chao-Yang, Guevara Hugo, Wadford Debra, Miller Steve, Mason Christopher E, Chiu Charles Y

2021-Feb