{"doi":"10.1101/2021.02.22.21252237","title":"Group IIA Secreted Phospholipase A <sub>2</sub> Plays a Central Role in the Pathobiology of COVID-19","abstract":"Abstract There is an urgent need to identify cellular and molecular mechanisms responsible for severe COVID-19 disease accompanied by multiple organ failure and high mortality rates. Here, we performed untargeted/targeted lipidomics and focused biochemistry on 127 patient plasma samples, and showed high levels of circulating, enzymatically active secreted phospholipase A 2 Group IIA (sPLA 2 -IIA) in severe and fatal COVID-19 disease compared with uninfected patients or mild illness. Machine learning demonstrated that sPLA 2 -IIA effectively stratifies severe from fatal COVID-19 disease. We further introduce a PLA-BUN index that combines sPLA 2 -IIA and blood urea nitrogen (BUN) threshold levels as a critical risk factor for mitochondrial dysfunction, sustained inflammatory injury and lethal COVID-19. With the availability of clinically tested inhibitors of sPLA 2 -IIA, our study opens the door to a precision intervention using indices discovered here to reduce COVID-19 mortality.","journal":"medRxiv","year":2021,"id":215032,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":469772,"name":"Jeehyun Karen You","orcid":"0000-0001-6705-022X","position":1,"is_corresponding":false},{"id":809253,"name":"Xia Wang","orcid":"0009-0008-6521-4938","position":2,"is_corresponding":false},{"id":316842,"name":"Ashley J. Snider","orcid":"0000-0002-1515-4171","position":3,"is_corresponding":false},{"id":263814,"name":"Brian Hallmark","orcid":"0000-0002-6790-0471","position":4,"is_corresponding":false},{"id":324993,"name":"Michael C. Seeds","orcid":null,"position":5,"is_corresponding":false},{"id":367199,"name":"Susan Sergeant","orcid":"0000-0002-8000-7573","position":6,"is_corresponding":false},{"id":91098,"name":"Laurel Johnstone","orcid":"0000-0001-7335-3972","position":7,"is_corresponding":false},{"id":809766,"name":"Qiuming Wang","orcid":null,"position":8,"is_corresponding":false},{"id":231646,"name":"Ryan Sprissler","orcid":"0000-0001-9250-2320","position":9,"is_corresponding":false},{"id":449341,"name":"Hao Helen Zhang","orcid":"0000-0001-8873-3329","position":10,"is_corresponding":false},{"id":570406,"name":"Chiara Luberto","orcid":null,"position":11,"is_corresponding":false},{"id":809254,"name":"Richard R. Kew","orcid":"0000-0002-4482-7179","position":12,"is_corresponding":false},{"id":271166,"name":"Yusuf A. Hannun","orcid":"0000-0003-3349-3369","position":13,"is_corresponding":false},{"id":483155,"name":"Charles E. McCall","orcid":"0000-0002-9082-469X","position":14,"is_corresponding":false},{"id":535483,"name":"Guang Yao","orcid":"0000-0003-3238-8479","position":15,"is_corresponding":false},{"id":329325,"name":"Maurizio Del Poeta","orcid":"0000-0001-8418-3120","position":16,"is_corresponding":false},{"id":263815,"name":"Floyd H. Chilton","orcid":"0000-0002-3686-0198","position":17,"is_corresponding":false},{"id":367195,"name":"Justin M. Snider","orcid":"0000-0003-4102-698X","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:52:51.201033Z","pmid":"33655264","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":[]}