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

Jeffrey R Strich; Marcos J Ramos-Benitez; Davide Randazzo; Sydney R Stein; Ashley Babyak; Richard T Davey; Anthony F Suffredini; Richard W Childs; Daniel S Chertow

doi:10.1093/infdis/jiaa789

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

J Infect Dis. 2021 Mar 29;223(6):981-984. doi: 10.1093/infdis/jiaa789.

Authors

Jeffrey R Strich^{1

2}, Marcos J Ramos-Benitez¹, Davide Randazzo³, Sydney R Stein¹, Ashley Babyak¹, Richard T Davey⁴, Anthony F Suffredini¹, Richard W Childs^{2

5}, Daniel S Chertow^{1

2

4}

Affiliations

¹ Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
² United States Public Health Service Commissioned Corps, Rockville, Maryland, USA.
³ Light Imaging Section, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bethesda, Maryland, USA.
⁴ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
⁵ Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.

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.

Published by Oxford University Press for the Infectious Diseases Society of America 2020.

MeSH terms

Aminopyridines
COVID-19 / blood
COVID-19 / pathology
COVID-19 Drug Treatment*
Extracellular Traps / drug effects*
Humans
Morpholines
Neutrophils / drug effects*
Oxazines / pharmacology*
Pyridines / pharmacology*
Pyrimidines
SARS-CoV-2 / isolation & purification

Substances

Aminopyridines
Morpholines
Oxazines
Pyridines
Pyrimidines
fostamatinib

Associated data

ClinicalTrials.gov/NCT04579393