OBJECTIVES: Infection with the novel coronavirus SARS-CoV-2 triggers severe illness with high mortality in a subgroup of patients . Such critical course of coronavirus disease (COVID) -19 is thought to associate with cytokine storm as in macrophage activation syndrome (MAS) or secondary hemophagocytic lymphohistiocytosis (sHLH), although these specific data are still lacking . In this study we aimed to directly address the question, whether immune activation in COVID-19 does indeed mimic conditions as in these classical cytokine storm syndromes .
METHODS: We quantified levels of 22 biomarkers in serum samples of COVID-19 (n=30, n=83 longitudinal samples in total), sHLH/MAS patients (n=50) as well as healthy controls (n=9) using bead array assay as well as single-marker ELISA and correlated results with disease outcome .
RESULTS: In sHLH/MAS we observed dramatic activation of the interleukin (IL) -18-interferon (IFN) -Î³ axis, while increased serum levels of IL-1 receptor antagonist (IL-1Ra), intracellular adhesion molecule 1 (ICAM-1) and IL-8, as well as strongly reduced levels of soluble Fas ligand (sFasL) in course of SARS-CoV-2 infection discriminate immune dysregulation in critical COVID-19 from the investigated well-recognized cytokine storm conditions .
CONCLUSIONS: Serum biomarker profiles clearly separate COVID-19 from MAS or sHLH, which questions the significance of systemic hyperinflammation following SARS-CoV-2 infection as well as the efficacy of drugs targeting key molecules and pathways specifically associated with systemic cytokine storm conditions in the treatment of COVID-19.