RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections

Richard Wargodsky, Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Philip Dela Cruz, Department Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
John LaFleur, Department of Emergency Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
David Yamane, Department Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Justin Sungmin Kim, Department Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Ivy Benjenk, Department Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Eric Heinz, Department Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Obinna Ome Irondi, Department Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Katherine Farrar, Department Anesthesiology and Critical Care Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Ian Toma, Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Tristan Jordan, Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Jennifer Goldman, Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, Washington, DC, United States of America.
Timothy A. McCaffrey, Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, Washington, DC, United States of America.

Document Type

Journal Article

Publication Date

1-1-2022

Journal

PloS one

Volume

17

Issue

1

DOI

10.1371/journal.pone.0261679

Abstract

Infection with the SARS-CoV2 virus can vary from asymptomatic, or flu-like with moderate disease, up to critically severe. Severe disease, termed COVID-19, involves acute respiratory deterioration that is frequently fatal. To understand the highly variable presentation, and identify biomarkers for disease severity, blood RNA from COVID-19 patient in an intensive care unit was analyzed by whole transcriptome RNA sequencing. Both SARS-CoV2 infection and the severity of COVID-19 syndrome were associated with up to 25-fold increased expression of neutrophil-related transcripts, such as neutrophil defensin 1 (DEFA1), and 3-5-fold reductions in T cell related transcripts such as the T cell receptor (TCR). The DEFA1 RNA level detected SARS-CoV2 viremia with 95.5% sensitivity, when viremia was measured by ddPCR of whole blood RNA. Purified CD15+ neutrophils from COVID-19 patients were increased in abundance and showed striking increases in nuclear DNA staining by DAPI. Concurrently, they showed >10-fold higher elastase activity than normal controls, and correcting for their increased abundance, still showed 5-fold higher elastase activity per cell. Despite higher CD15+ neutrophil elastase activity, elastase activity was extremely low in plasma from the same patients. Collectively, the data supports the model that increased neutrophil and decreased T cell activity is associated with increased COVID-19 severity, and suggests that blood DEFA1 RNA levels and neutrophil elastase activity, both involved in neutrophil extracellular traps (NETs), may be informative biomarkers of host immune activity after viral infection.

Department

Genomics and Precision Medicine

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