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

Affiliation

Ng DL(1)(2), Granados AC(2)(3), Santos YA(2)(3), Servellita V(2)(3), Goldgof GM(2), Meydan C(4)(5)(6), Sotomayor-Gonzalez A(2)(3), Levine AG(2), Balcerek J(2), Han LM(1), Akagi N(1), Truong K(1), Neumann NM(1), Nguyen DN(7), Bapat SP(2)(7)(8), Cheng J(9)(10), Martin CS(2)(3), Federman S(2)(3), Foox J(4)(5)(6), Gopez A(2)(3), Li T(11), Chan R(2), Chu CS(2), Wabl CA(2)(3), Gliwa AS(2)(3), Reyes K(2)(3), Pan CY(12), Guevara H(12), Wadford D(12), Miller S(2)(3), Mason CE(4)(5)(13)(14), Chiu CY(15)(3)(8).
Author information:
(1)Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
(2)Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
(3)UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA.
(4)Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
(5)The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
(6)WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA.
(7)Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
(8)Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA.
(9)Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, CA, USA.
(10)Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
(11)Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA, USA.
(12)Viral and Rickettsial Disease Laboratory, California Department of Health, Richmond, CA, USA.
(13)New York Genome Center, New York, NY, USA.
(14)Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
(15)Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA. [Email]

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.