A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood
Dianna L. Ng1,2,*, View ORCID ProfileAndrea C. Granados2,3,*, Yale A. Santos2,3,*, View ORCID ProfileVenice Servellita2,3,*, View ORCID ProfileGregory M. Goldgof2,...
Science Advances 03 Feb 2021:
Vol. 7, no. 6, eabe5984
DOI: 10.1126/sciadv.abe5984
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.