Article ; Online: RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections.
2022 Volume 17, Issue 1, Page(s) e0261679
Abstract: ... of whole blood RNA. Purified CD15+ neutrophils from COVID-19 patients were increased in abundance and ... transcriptome RNA sequencing. Both SARS-CoV2 infection and the severity of COVID-19 syndrome were associated ... for disease severity, blood RNA from COVID-19 patient in an intensive care unit was analyzed by whole ...
| 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. |
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| MeSH term(s) | Adult ; Biomarkers/blood ; COVID-19/diagnosis ; COVID-19/pathology ; COVID-19/virology ; Female ; Humans ; Intensive Care Units ; Lewis X Antigen/metabolism ; Male ; Middle Aged ; Neutrophil Activation ; Neutrophils/cytology ; Neutrophils/immunology ; Neutrophils/metabolism ; Pancreatic Elastase/blood ; RNA, Viral/chemistry ; RNA, Viral/metabolism ; Receptors, Antigen, T-Cell/genetics ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Sensitivity and Specificity ; Sequence Analysis, RNA ; Severity of Illness Index ; alpha-Defensins/genetics |
| Chemical Substances | Biomarkers ; Lewis X Antigen ; RNA, Viral ; Receptors, Antigen, T-Cell ; alpha-Defensins ; human neutrophil peptide 1 ; Pancreatic Elastase (EC 3.4.21.36) |
| Language | English |
| Publishing date | 2022-01-26 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2267670-3 |
| ISSN | 1932-6203 ; 1932-6203 |
| ISSN (online) | 1932-6203 |
| ISSN | 1932-6203 |
| DOI | 10.1371/journal.pone.0261679 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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