{"doi":"10.1093/infdis/jiae318","title":"Precision Symptom Phenotyping Identifies Early Clinical and Proteomic Predictors of Distinct COVID-19 Sequelae","abstract":"BACKGROUND: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints. METHODS: This analysis included 1988 SARS-CoV-2 positive U.S. Military Health System beneficiaries who had quantitative post-COVID symptom scores. Among participants who reported moderate-to-severe symptoms on surveys collected 6 months post-SARS-CoV-2 infection, principal component analysis followed by k-means clustering identified distinct clusters of symptoms. RESULTS: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization than those with no/mild symptoms at 6 months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking and elevated ICAM-1 concentrations to sensory symptoms. CONCLUSIONS: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.","journal":"The Journal of Infectious Diseases","year":2024,"id":426053,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8133,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":670631,"name":"Josh Chenoweth","orcid":"0009-0003-9693-5010","position":1,"is_corresponding":false},{"id":391331,"name":"Paul W. Blair","orcid":"0000-0002-3817-5987","position":2,"is_corresponding":false},{"id":670628,"name":"David A Lindholm","orcid":"0000-0001-5428-7404","position":3,"is_corresponding":false},{"id":427625,"name":"Anuradha Ganesan","orcid":null,"position":4,"is_corresponding":false},{"id":426930,"name":"Tahaniyat Lalani","orcid":"0000-0002-9361-2991","position":5,"is_corresponding":false},{"id":690026,"name":"Alfred G. Smith","orcid":null,"position":6,"is_corresponding":false},{"id":689161,"name":"Rupal Mody","orcid":"0000-0003-3862-4495","position":7,"is_corresponding":false},{"id":696873,"name":"Milissa U. Jones","orcid":"0009-0009-1798-2753","position":8,"is_corresponding":false},{"id":514704,"name":"Rhonda E Colombo","orcid":"0000-0003-0154-1928","position":9,"is_corresponding":false},{"id":670630,"name":"Christopher Colombo","orcid":"0000-0001-5499-3368","position":10,"is_corresponding":false},{"id":449838,"name":"Christina Schofield","orcid":"0000-0002-0367-4495","position":11,"is_corresponding":false},{"id":670633,"name":"Evan Ewers","orcid":"0000-0002-1384-9973","position":12,"is_corresponding":false},{"id":670634,"name":"Derek Larson","orcid":"0000-0002-6147-7182","position":13,"is_corresponding":false},{"id":670641,"name":"Catherine M Berjohn","orcid":"0000-0001-5655-8183","position":14,"is_corresponding":false},{"id":404704,"name":"Ryan C. Maves","orcid":"0000-0001-6234-6160","position":15,"is_corresponding":false},{"id":696869,"name":"Anthony C Fries","orcid":"0000-0001-7556-1353","position":16,"is_corresponding":false},{"id":459633,"name":"David C. Chang","orcid":"0000-0002-1414-1280","position":17,"is_corresponding":false},{"id":1225448,"name":"Andrew Wyatt","orcid":null,"position":18,"is_corresponding":false},{"id":386188,"name":"I Scher","orcid":"0000-0003-4599-9834","position":19,"is_corresponding":false},{"id":420631,"name":"Celia Byrne","orcid":"0000-0001-8289-4252","position":20,"is_corresponding":false},{"id":485025,"name":"Jennifer A. Rusiecki","orcid":"0000-0003-3881-8695","position":21,"is_corresponding":false},{"id":290869,"name":"David Saunders","orcid":"0000-0003-0946-1164","position":22,"is_corresponding":false},{"id":689167,"name":"Jeffrey Livezey","orcid":"0000-0001-9748-095X","position":23,"is_corresponding":false},{"id":647753,"name":"Allison M. W. Malloy","orcid":"0000-0003-2962-0302","position":24,"is_corresponding":false},{"id":689162,"name":"Samantha Bazan","orcid":"0000-0002-9812-5164","position":25,"is_corresponding":false},{"id":690034,"name":"Carlos J Maldonado","orcid":null,"position":26,"is_corresponding":false},{"id":860433,"name":"Margaret Edwards","orcid":"0000-0001-9803-509X","position":27,"is_corresponding":false},{"id":559650,"name":"Katrin Mende","orcid":null,"position":28,"is_corresponding":false},{"id":272091,"name":"Mark P. Simons","orcid":"0000-0002-4316-9709","position":29,"is_corresponding":false},{"id":392403,"name":"Robert J. O’Connell","orcid":"0000-0001-8901-1432","position":30,"is_corresponding":false},{"id":426929,"name":"David R. Tribble","orcid":"0000-0003-3077-9505","position":31,"is_corresponding":false},{"id":404703,"name":"Brian K. Agan","orcid":"0000-0002-5114-1669","position":32,"is_corresponding":false},{"id":103453,"name":"Timothy Burgess","orcid":"0000-0003-1247-8370","position":33,"is_corresponding":false},{"id":650258,"name":"Simon Pollett","orcid":"0000-0003-2643-4213","position":34,"is_corresponding":false},{"id":536243,"name":"Stephanie A Richard","orcid":"0000-0002-0530-384X","position":35,"is_corresponding":false},{"id":557984,"name":"Nusrat J Epsi","orcid":"0000-0001-5363-075X","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:58:37.924718Z","pmid":"38916431","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":[]}