Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic

Abstract

Neutrophil extracellular traps (NETs) contribute to immunothrombosis and have been associated with mortality in coronavirus disease 2019 (COVID-19). We stimulated donor neutrophils with plasma from patients with COVID-19 and demonstrated that R406 can abrogate the release of NETs. These data provide evidence for how fostamatinib may mitigate neutrophil-associated mechanisms contributing to COVID-19 immunopathogenesis.

Trial registration: ClinicalTrials.gov NCT04579393.

Keywords: COVID-19; fostamatinib; immunothrombosis; neutrophil extracellular traps.

Figure 1.

R406 inhibits NETosis induced by plasma from COVID-19 patients. A, Representative images (10 ×) displaying the kinetics of NETs release visualized using the IncuCyte NETosis assay at 1, 3, and 6 hours comparing stimulation by healthy controls, plasma from a patient with COVID-19, PMA as a positive control, and R406 inhibition (4 μM) of plasma from a patient with COVID-19 and PMA. B, RFU at 6 hours after stimulation were used to compared groups using a Student t test. Horizontal dashed lines represent mean value of each group. Abbreviations: COVID-19, coronavirus disease 2019; NET, neutrophil extracellular trap; PMA, phorbol myristate ester; RFU, relative fluorescent unit.