{"doi":"10.1371/journal.pone.0261679","title":"RNA Sequencing in COVID-19 patients identifies neutrophil activation biomarkers as a promising diagnostic platform for infections","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.","journal":"PLoS ONE","year":2022,"id":246199,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":882012,"name":"Philip Dela Cruz","orcid":"0000-0001-6964-3563","position":1,"is_corresponding":false},{"id":882013,"name":"John Lafleur","orcid":"0000-0003-4404-2723","position":2,"is_corresponding":false},{"id":882014,"name":"David Yamane","orcid":"0000-0002-5101-2162","position":3,"is_corresponding":false},{"id":882753,"name":"Justin Sungmin Kim","orcid":null,"position":4,"is_corresponding":false},{"id":750985,"name":"Ivy Benjenk","orcid":"0000-0002-5057-9300","position":5,"is_corresponding":false},{"id":882015,"name":"Eric Heinz","orcid":"0000-0002-3194-8553","position":6,"is_corresponding":false},{"id":882016,"name":"Obinna Ome Irondi","orcid":"0000-0001-5453-9456","position":7,"is_corresponding":false},{"id":882017,"name":"Katherine Farrar","orcid":"0000-0002-1846-9611","position":8,"is_corresponding":false},{"id":696329,"name":"Ian Toma","orcid":"0000-0002-9637-5899","position":9,"is_corresponding":false},{"id":882018,"name":"Tristan Jordan","orcid":"0000-0003-0943-5935","position":10,"is_corresponding":false},{"id":882019,"name":"Jennifer Goldman","orcid":"0000-0003-2651-8767","position":11,"is_corresponding":false},{"id":696328,"name":"Timothy A. McCaffrey","orcid":"0000-0002-4648-7833","position":12,"is_corresponding":false},{"id":697201,"name":"Richard Wargodsky","orcid":null,"position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T00:23:43.438539Z","pmid":"35081105","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}