BioAcyl Corp |
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| Resource type: Journal Article DOI: 10.1172/jci.insight.140329 BibTeX citation key: Remy2020 View all bibliographic details |
Categories: BioAcyl Corp, Zotero Subcategories: COVID-19 Creators: Anand, Blood, Blood, Bosanquet, Brakenridge, Caldwell, Drewry, Ellebedy, Hotchkiss, Mannion, Martin, Mazer, Moldawer, Mudd, Osborne, Remy, Striker, Turnbull, Unsinger, Walton, Yi Collection: JCI Insight |
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| Abstract |
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COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: a hyper-inflammatory ‘cytokine-storm’-mediated injury versus failure of host protective immunity resulting in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay was employed in 27 COVID-19, 51 septic, 18 critically-ill non-septic (CINS), and 27 healthy controls to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ and monocyte TFN-α production. Circulating T cell subsets were profoundly reduced in COVID-19 patients. Additionally, stimulated blood mononuclear cells produced less than 40% to 50% of the IFN-ɣ and TNF-α observed in septic and CINS patients, consistent with markedly impaired immune effector cell function. Approximately 25% of COVID-19 patients had increased IL-6 levels greater than 1,000 pg/mL that were not associated with elevations in other canonical pro-inflammatory cytokines. Collectively, these findings support the hypothesis that COVID-19 suppresses host functional adaptive and innate immunity. Importantly, Interleukin-7 administered ex vivo restored T cell IFN-ɣ production in COVID-19 patients. Thus, ELISpot may functionally characterize host immunity in COVID-19 and inform prospective therapies.
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