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

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 d...

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Autores principales: Wargodsky, Richard, Dela Cruz, Philip, LaFleur, John, Yamane, David, Kim, Justin Sungmin, Benjenk, Ivy, Heinz, Eric, Irondi, Obinna Ome, Farrar, Katherine, Toma, Ian, Jordan, Tristan, Goldman, Jennifer, McCaffrey, Timothy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791486/
https://www.ncbi.nlm.nih.gov/pubmed/35081105
http://dx.doi.org/10.1371/journal.pone.0261679
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author Wargodsky, Richard
Dela Cruz, Philip
LaFleur, John
Yamane, David
Kim, Justin Sungmin
Benjenk, Ivy
Heinz, Eric
Irondi, Obinna Ome
Farrar, Katherine
Toma, Ian
Jordan, Tristan
Goldman, Jennifer
McCaffrey, Timothy A.
author_facet Wargodsky, Richard
Dela Cruz, Philip
LaFleur, John
Yamane, David
Kim, Justin Sungmin
Benjenk, Ivy
Heinz, Eric
Irondi, Obinna Ome
Farrar, Katherine
Toma, Ian
Jordan, Tristan
Goldman, Jennifer
McCaffrey, Timothy A.
author_sort Wargodsky, Richard
collection PubMed
description 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.
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spelling pubmed-87914862022-01-27 RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections Wargodsky, Richard Dela Cruz, Philip LaFleur, John Yamane, David Kim, Justin Sungmin Benjenk, Ivy Heinz, Eric Irondi, Obinna Ome Farrar, Katherine Toma, Ian Jordan, Tristan Goldman, Jennifer McCaffrey, Timothy A. PLoS One Research Article 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. Public Library of Science 2022-01-26 /pmc/articles/PMC8791486/ /pubmed/35081105 http://dx.doi.org/10.1371/journal.pone.0261679 Text en © 2022 Wargodsky et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wargodsky, Richard
Dela Cruz, Philip
LaFleur, John
Yamane, David
Kim, Justin Sungmin
Benjenk, Ivy
Heinz, Eric
Irondi, Obinna Ome
Farrar, Katherine
Toma, Ian
Jordan, Tristan
Goldman, Jennifer
McCaffrey, Timothy A.
RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections
title RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections
title_full RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections
title_fullStr RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections
title_full_unstemmed RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections
title_short RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections
title_sort rna sequencing in covid-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791486/
https://www.ncbi.nlm.nih.gov/pubmed/35081105
http://dx.doi.org/10.1371/journal.pone.0261679
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