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. ELISpot, a highly sensitive, functional immunoassay, suggests that COVID-19 is immunosuppressive and lacks substantial cytokine storm.
【저자키워드】 COVID-19, Adaptive immunity, 【초록키워드】 Cytokine storm, adaptive, Innate immunity, diagnostic, Sepsis, cytokine, host response, monocyte, immunoassay, T cell, Critically ill, protective immunity, Patient, immune function, morbidity and mortality, ELISPOT, proinflammatory cytokines, dissemination, patients, COVID-19 patients, Blood, Therapies, TNF-α, IL-7, innate immune, Hypothesis, immunosuppressive, COVID-19 patient, mononuclear cell, Support, Ex vivo, healthy control, host immunity, COVID-19 infections, Elevation, organ injury, Administered, Host, Volunteer, Hyperinflammatory, stimulated, produced, lack, evaluate, pathologic, reduced, functional, less, suppresse, restored, hypothese, canonical, T cell subset, IL-6 level, immune effector cell, patients with COVID-19, 【제목키워드】 Cytokine storm, Immunosuppression, COVID-19 infection,