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

Autor: Richard Wargodsky, Philip Dela Cruz, John LaFleur, David Yamane, Justin Sungmin Kim, Ivy Benjenk, Eric Heinz, Obinna Ome Irondi, Katherine Farrar, Ian Toma, Tristan Jordan, Jennifer Goldman, Timothy A. McCaffrey
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Male
Viral Diseases
Neutrophils
Physiology
Molecular biology
Severity of Illness Index
Biochemistry
Immune Receptors
Neutrophil Activation
White Blood Cells
Medical Conditions
Sequencing techniques
Animal Cells
Medicine and Health Sciences
Immune System Proteins
Multidisciplinary
Pancreatic Elastase
T Cells
RNA sequencing
Middle Aged
Body Fluids
Intensive Care Units
Infectious Diseases
Blood
RNA
Viral
Medicine
Female
Cellular Types
Anatomy
Research Article
Signal Transduction
Adult
alpha-Defensins
Immune Cells
Science
Immunology
Receptors
Antigen
T-Cell
Lewis X Antigen
Sensitivity and Specificity
Humans
Blood Cells
SARS-CoV-2
Sequence Analysis
RNA
COVID-19
Biology and Life Sciences
Proteins
Covid 19
Cell Biology
T Cell Receptors
Research and analysis methods
Blood Counts
Molecular biology techniques
Biomarkers
Zdroj: PLoS ONE, Vol 17, Iss 1, p e0261679 (2022)
PLoS ONE, Vol 17, Iss 1 (2022)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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