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Immune dysregulation associated with COVID-19 includes immune cell activation, inflammatory cytokine release, and neutrophil extracellular trap release (NETosis), which are mediated by spleen tyrosine kinase (SYK) (Fig 1). Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, was approved for immune thrombocytopenia (ITP) in 2018, and the Phase 3 trials showed a lower than expected rate of thrombosis.¹ Clinical studies showed a reduction in IL-6 in patients with rheumatoid arthritis.² The active metabolite of fostamatinib (R406) protected against LPS-induced acute lung injury and thrombosis in mice^3,4 and reduced MUC1 in a mouse model of ALI.⁵ Fostamatinib demonstrated abrogation of the hyperimmune response caused by anti-spike IgG,⁶ including reduction in hyperactivation of platelets⁷ and NETosis in neutrophils⁸ in in vitro studies using plasma from patients …