Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19.

ABSTRACT: Spleen tyrosine kinase (SYK) is a previously unidentified therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial. We demonstrated that SYK inhibition was associated with reduced neutrophil activation, increased circulation of mature neutrophils (CD10⁺CD33^-), and decreased circulation of low-density granulocytes and polymorphonuclear myeloid-derived suppressor cells (HLA-DR^-CD33⁺CD1

SUBMITTER: Wigerblad G 

PROVIDER: S-EPMC9812373 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature