1. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections.
- Author
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Remy KE, Mazer M, Striker DA, Ellebedy AH, Walton AH, Unsinger J, Blood TM, Mudd PA, Yi DJ, Mannion DA, Osborne DF, Martin RS, Anand NJ, Bosanquet JP, Blood J, Drewry AM, Caldwell CC, Turnbull IR, Brakenridge SC, Moldwawer LL, and Hotchkiss RS
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Betacoronavirus, COVID-19, Case-Control Studies, Critical Illness, Enzyme-Linked Immunospot Assay, Female, Healthy Volunteers, Humans, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-6 immunology, Male, Middle Aged, Monocytes immunology, Monocytes metabolism, Pandemics, SARS-CoV-2, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, T-Lymphocytes immunology, T-Lymphocytes metabolism, Tumor Necrosis Factor-alpha immunology, Tumor Necrosis Factor-alpha metabolism, Young Adult, Adaptive Immunity immunology, Coronavirus Infections immunology, Cytokine Release Syndrome immunology, Immune Tolerance immunology, Immunity, Innate immunology, Pneumonia, Viral immunology, Sepsis immunology
- Abstract
COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results 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 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers 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%-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 that were not associated with elevations in other canonical proinflammatory cytokines. Collectively, these findings support the hypothesis that COVID-19 suppresses host functional adaptive and innate immunity. Importantly, IL-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.
- Published
- 2020
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