{"doi":"10.1159/000545432","title":"Patients Hospitalized with COVID-19 Demonstrate Distinct Plasma Cytokine and Chemokine Concentrations in vivo and TLR-Mediated Cytokine and Chemokine Production in Whole Blood in vitro","abstract":"INTRODUCTION: SARS-CoV-2's continued global health impact underscores the importance of ongoing pathogenesis research. Insights into the host's first line of defense against severe COVID-19 identify actionable biomarkers, informing disease management or therapeutics. Yet, the innate immune response, including cytokines, chemokines, adenosine deaminases (ADAs) and Toll-like receptors (TLRs), relevant to COVID-19 remain incompletely characterized. METHODS: Peripheral blood was longitudinally collected between May 2020 and March 2021 from COVID-19 hospitalized adults (N = 79) and healthy controls (HCs) (N = 14; not tested, assumed COVID-negative, no viral exposure or symptoms). Heparinized blood was fractionated for plasma cryopreservation and in vitro whole blood TLR-stimulation employing TLR-3, -4, and -7/8 agonists. Post-stimulation culture supernatants were analyzed using multiplex and enzymatic assays. RESULTS: Upon hospitalization, plasma concentrations of IFNγ, IL-6, CXCL10, and ADAs were significantly upregulated compared to convalescent time points and HCs. Participants with fatal COVID-19 exhibited higher IL-27, CXCL10, and ADAs concentrations upon admission. Plasma cytokines, chemokines, and ADAs were positively correlated and associated with distinct temporal patterns. TLR-stimulated cell cultures from patients produced reduced IFNα2, IFNγ, IL-12p40, and IL-12p70 compared to HCs or later time points. CONCLUSION: Higher plasma concentrations of IL-27, CXCL10, and ADAs at admission were associated with severe COVID-19 and mortality. Reduced TLR-mediated IFNα2, IFNγ, and IL-12p70 production suggests COVID dampens Th1-polarizing innate immune responses, providing insight into immunological sequelae of SARS-CoV-2 infection.","journal":"Journal of Innate Immunity","year":2025,"id":532445,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1321980,"name":"Thomas S Kouyate","orcid":null,"position":1,"is_corresponding":false},{"id":1275049,"name":"Kevin Ryff","orcid":"0009-0000-3112-0687","position":2,"is_corresponding":false},{"id":758442,"name":"Alec L. Plotkin","orcid":"0000-0003-3831-9845","position":3,"is_corresponding":false},{"id":719477,"name":"Simon Doss-Gollin","orcid":"0000-0001-8797-7452","position":4,"is_corresponding":false},{"id":855790,"name":"Sanya Thomas","orcid":"0000-0003-3648-9461","position":5,"is_corresponding":false},{"id":266219,"name":"Kerry McEnaney","orcid":"0000-0002-0378-3456","position":6,"is_corresponding":false},{"id":266217,"name":"Al Ozonoff","orcid":"0000-0003-4233-5899","position":7,"is_corresponding":false},{"id":266205,"name":"Joann Diray‐Arce","orcid":"0000-0003-2183-4269","position":8,"is_corresponding":false},{"id":266198,"name":"Ofer Levy","orcid":"0000-0002-5859-1945","position":9,"is_corresponding":false},{"id":398024,"name":"Oludare A. Odumade","orcid":"0000-0002-8630-8510","position":10,"is_corresponding":false},{"id":3841,"name":"Lindsey R. Baden","orcid":null,"position":11,"is_corresponding":false},{"id":266208,"name":"Simon D. van Haren","orcid":"0000-0002-1791-0161","position":12,"is_corresponding":false},{"id":266216,"name":"Kinga K. Smolen","orcid":"0000-0001-8650-3693","position":13,"is_corresponding":false},{"id":1414001,"name":"On behalf of the IMPACC - Boston Team","orcid":null,"position":14,"is_corresponding":false},{"id":1321575,"name":"Athena N. Nguyen","orcid":"0000-0001-6779-1159","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:51:23.237536Z","pmid":"40435967","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":[]}