Inhibition of Bruton tyrosine kinase in patients with severe COVID-19

Corresponding author: Wyndham H. Wilson

Affiliation: Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD, USA; Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA; Willamette Valley Cancer Institute and Research Center, US Oncology, Eugene, OR, USA; Hematology-Oncology Department, Walter Reed National Military Medical Center, Bethesda, MD, USA; John Theurer Cancer Center, Hackensack Meridian and School of Medicine at Seton Hall, NJ, USA; Rocky Mountain Cancer Center, US Oncology, Colorado Springs, CO, USA; Department of Emergency Medicine, Penrose-St. Francis Health Services, Colorado Springs, CO, USA; US Acute Care Solutions, Canton, OH, USA; Department of Medicine, St. Peter’s Hospital and US Oncology, Albany, NY, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Acerta Pharma, South San Francisco, CA, USA; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD, USA; AstraZeneca, One MedImmune Way, Gaithersburg, MD, USA.

Publication date: this article was published online on June 05, 2020

DOI: 10.1126/sciimmunol.abd0110

Highlights

The researchers conducted an observational study evaluating off-label use of acalabrutinib, an inhibitor of the Bruton tyrosine kinase (BTK) enzyme, in 19 hospitalized COVID-19 patients requiring oxygen supplementation. At the end of acalabrutinib treatment, 8 of 11 (72.7%) patients in the supplemental oxygen cohort had been discharged on room air, and 4 of 8 (50%) patients in the mechanical ventilation cohort had been successfully extubated, with 2 of 8 (25%) discharged on room air. Ex vivo analysis revealed significantly elevated BTK activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers.

Nomination Reasons

The data present in this article suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.

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