At the request of the Investigators, the GWU IRB, and the GW Office of Research Integrity, access to sequence-level data will be made available by contacting the GWU IRB at The human genome files for alignment were obtained from UCSC at this link for HG38 ( ).įunding: The authors are grateful for the generous financial support of True Bearing Diagnostics, Inc., The St.
To protect the anonymity of the research subjects, the raw sequence files from this study will be provided to qualified investigators that can ensure compliance with appropriate IRB and HIPAA regulations for any future data usage. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: The expression-level data (raw RPKM) is deposited in the Gene Expression Omnibus (GEO) at the accession #GSE189990.
Received: SeptemAccepted: DecemPublished: January 26, 2022Ĭopyright: © 2022 Wargodsky et al. PLoS ONE 17(1):Įditor: Afsheen Raza, Hamad Medical Corporation, QATAR (2022) RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections. 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.Ĭitation: Wargodsky R, Dela Cruz P, LaFleur J, Yamane D, Kim JS, Benjenk I, et al. Despite higher CD15+ neutrophil elastase activity, elastase activity was extremely low in plasma from the same patients. 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. Purified CD15+ neutrophils from COVID-19 patients were increased in abundance and showed striking increases in nuclear DNA staining by DAPI. The DEFA1 RNA level detected SARS-CoV2 viremia with 95.5% sensitivity, when viremia was measured by ddPCR of whole blood RNA. 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). 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. Severe disease, termed COVID-19, involves acute respiratory deterioration that is frequently fatal. Infection with the SARS-CoV2 virus can vary from asymptomatic, or flu-like with moderate disease, up to critically severe.
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