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Remy, K. E., Mazer, M., Striker, D. A., Ellebedy, A. H., Walton, A. H., & Unsinger, J., et al. (2020). Severe immunosuppression and not a cytokine storm characterize covid-19 infections. JCI Insight. 
Added by: Dr. Enrique Feoli (06/08/2020, 09:45)   Last edited by: Dr. Enrique Feoli (06/08/2020, 19:55)
Resource type: Journal Article
DOI: 10.1172/jci.insight.140329
BibTeX citation key: Remy2020
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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
Views: 1/267
Abstract
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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