Abstract
Objective: Infection with the novel coronavirus SARS-CoV-2 triggers severe illness with high mortality in a subgroup of patients. Such a critical course of COVID-19 is thought to be associated with the development of cytokine storm, a condition seen in macrophage activation syndrome (MAS) and secondary hemophagocytic lymphohistiocytosis (HLH). However, specific data demonstrating a clear association of cytokine storm with severe COVID-19 are still lacking. The aim of this study was to directly address whether immune activation in COVID-19 does indeed mimic the conditions found in these classic cytokine storm syndromes.
Methods: Levels of 22 biomarkers were quantified in serum samples from patients with COVID-19 (n = 30 patients, n = 83 longitudinal samples in total), patients with secondary HLH/MAS (n = 50), and healthy controls (n = 9). Measurements were performed using bead array assays and single-marker enzyme-linked immunosorbent assay. Serum biomarker levels were assessed for correlations with disease outcome.
Results: In patients with secondary HLH/MAS, we observed pronounced activation of the interleukin-18 (IL-18)-interferon-γ axis, increased serum levels of IL-1 receptor antagonist, intercellular adhesion molecule 1, and IL-8, and strongly reduced levels of soluble Fas ligand in the course of SARS-CoV-2 infection. These observations appeared to discriminate immune dysregulation in critical COVID-19 from the well-recognized characteristics of other cytokine storm syndromes.
Conclusion: Serum biomarker profiles clearly separate COVID-19 from MAS or secondary HLH in terms of distinguishing the severe systemic hyperinflammation that occurs following SARS-CoV-2 infection. These findings could be useful in determining the efficacy of drugs targeting key molecules and pathways specifically associated with systemic cytokine storm conditions in the treatment of COVID-19.
【초록키워드】 COVID-19, Treatment, Macrophage, Efficacy, Cytokine storm, Biomarker, Biomarkers, severe COVID-19, SARS-COV-2 infection, interferon, cytokine, outcome, Novel coronavirus, enzyme-linked immunosorbent assay, interleukin, Characteristics, immune activation, hyperinflammation, Patient, pathway, IL-8, hemophagocytic lymphohistiocytosis, macrophage activation syndrome, correlation, secondary hemophagocytic lymphohistiocytosis, disease, Critical, patients, HLH, IL-1, association, Interleukin-18, Pathways, Trigger, immune dysregulation, triggers, dysregulation, classic, receptor antagonist, intercellular adhesion molecule, Adhesion Molecule, observation, Activation, treatment of COVID-19, serum samples, Serum level, profile, healthy control, serum levels, novel coronavirus SARS-CoV-2, high mortality, correlations, healthy controls, systemic hyperinflammation, serum sample, IL-1 receptor antagonist, longitudinal samples, measurement, soluble Fas ligand, enzyme-linked immunosorbent, thought, Course, performed, reduced, condition, occur, Level, drugs targeting, quantified, intercellular, patients with COVID-19, subgroup of patients, systemic cytokine, were assessed, 【제목키워드】 COVID-19, discrimination, storm,