{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:57:05Z","timestamp":1780491425374,"version":"3.54.1"},"reference-count":75,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"abstract":"<jats:p>Introduction: SARS-CoV-2\u2019s continued global health impact underscores the importance of ongoing pathogenesis research. Insights into the host\u2019s 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 IFN\u03b3, 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 IFN\u03b12, IFN\u03b3, 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 IFN\u03b12, IFN\u03b3, and IL-12p70 production suggests COVID dampens Th1-polarizing innate immune responses, providing insight into immunological sequelae of SARS-CoV-2 infection. <\/jats:p>","DOI":"10.1159\/000545432","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T16:02:11Z","timestamp":1748448131000},"page":"288-301","source":"Crossref","is-referenced-by-count":3,"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"],"prefix":"10.1159","volume":"17","author":[{"given":"Athena N.","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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