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.
Kenneth E. Remy, Monty Mazer, David A. Striker, Ali H. Ellebedy, Andrew H. Walton, Jacqueline Unsinger, Teresa M. Blood, Philip A. Mudd, Daehan J. Yi, Daniel A. Mannion, Dale F. Osborne, R. Scott Martin, Nitin J. Anand, James P. Bosanquet, Jane Blood, Anne M. Drewry, Charles C. Caldwell, Isaiah R. Turnbull, Scott C. Brakenridge, Lyle L. Moldawer, Richard S. Hotchkiss