TY - JOUR
T1 - Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections
AU - Remy, Kenneth E.
AU - Mazer, Monty
AU - Striker, David A.
AU - Ellebedy, Ali H.
AU - Walton, Andrew H.
AU - Unsinger, Jacqueline
AU - Blood, Teresa M.
AU - Mudd, Philip A.
AU - Yi, Daehan J.
AU - Mannion, Daniel A.
AU - Osborne, Dale F.
AU - Scott Martin, R.
AU - Anand, Nitin J.
AU - Bosanquet, James P.
AU - Blood, Jane
AU - Drewry, Anne M.
AU - Caldwell, Charles C.
AU - Turnbull, Isaiah R.
AU - Brakenridge, Scott C.
AU - Moldwawer, Lyle L.
AU - Hotchkiss, Richard S.
N1 - Publisher Copyright:
© 2020, Remy et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2020/9/3
Y1 - 2020/9/3
N2 - 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-γ 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-γ 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-γ production in COVID-19 patients. Thus, ELISpot may functionally characterize host immunity in COVID-19 and inform prospective therapies.
AB - 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-γ 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-γ 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-γ production in COVID-19 patients. Thus, ELISpot may functionally characterize host immunity in COVID-19 and inform prospective therapies.
UR - http://www.scopus.com/inward/record.url?scp=85090208333&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.140329
DO - 10.1172/jci.insight.140329
M3 - Article
C2 - 32687484
AN - SCOPUS:85090208333
SN - 2379-3708
VL - 5
JO - JCI Insight
JF - JCI Insight
IS - 17
M1 - e140329
ER -