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

  • Author(s): 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
  • et al.
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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