A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood

Dianna Ng(University of California, San Francisco), Andrea Granados(University of California, San Francisco), Yale Santos(University of California, San Francisco), Venice Servellita(University of California, San Francisco), Gregory M. Goldgof(University of California, San Francisco), Cem Meydan(Cornell University), Alicia Sotomayor-González(University of California, San Francisco), Andrew G. Levine(University of California, San Francisco), Joanna Balcerek(University of California, San Francisco), Lucy M. Han(University of California, San Francisco), Naomi Akagi(University of California, San Francisco), Kent Truong(University of California, San Francisco), Neil M. Neumann(University of California, San Francisco), David N. Nguyen(University of California, San Francisco), Sagar P. Bapat(University of California, San Francisco), Jing Cheng(University of California, San Francisco), Claudia Sánchez-San Martín(University of California, San Francisco), Scot Federman(University of California, San Francisco), Jonathan Foox(Cornell University), Allan Gopez(University of California, San Francisco), Tony Li(University of California, San Francisco), Ray Chun‐Fai Chan(University of California, San Francisco), Cynthia S. Chu(University of California, San Francisco), Chiara A. Wabl(University of California, San Francisco), Amelia S. Gliwa(University of California, San Francisco), Kevin Reyes(University of California, San Francisco), Chao‐Yang Pan(California Health and Human Services Agency), Hugo Guevara(California Health and Human Services Agency), Debra A. Wadford(California Health and Human Services Agency), Steve Miller(University of California, San Francisco), Christopher E. Mason(Cornell University), Charles Y. Chiu(University of California, San Francisco)
Science Advances
February 3, 2021
10.1126/sciadv.abe5984
Cited by 113Open Access
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Abstract

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.

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