A Scientific Rationale for Using Cystic Fibrosis Transmembrane Conductance Regulator Therapeutics in COVID-19 Patients

Darcy Lidington; Steffen-Sebastian Bolz

doi:10.3389/fphys.2020.583862

A Scientific Rationale for Using Cystic Fibrosis Transmembrane Conductance Regulator Therapeutics in COVID-19 Patients

Front Physiol. 2020 Nov 4:11:583862. doi: 10.3389/fphys.2020.583862. eCollection 2020.

Authors

Darcy Lidington^{1

2}, Steffen-Sebastian Bolz^{1

2

3}

Affiliations

¹ Department of Physiology, University of Toronto, Toronto, ON, Canada.
² Toronto Centre for Microvascular Medicine at The Ted Rogers Centre for Heart Research Translational Biology and Engineering Program, University of Toronto, Toronto, ON, Canada.
³ Heart and Stroke/Richard Lewar Centre of Excellence for Cardiovascular Research, University of Toronto, Toronto, ON, Canada.

Abstract

Several pathological manifestations in coronavirus disease 2019 (COVID-19), including thick mucus, poor mucociliary clearance, and bronchial wall thickening, overlap with cystic fibrosis disease patterns and may be indicative of "acquired" cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Indeed, tumor necrosis factor (TNF), a key cytokine driving COVID-19 pathogenesis, downregulates lung CFTR protein expression, providing a strong rationale that acquired CFTR dysfunction arises in the context of COVID-19 infection. In this perspective, we propose that CFTR therapeutics, which are safe and generally well-tolerated, may provide benefit to COVID-19 patients. Although CFTR therapeutics are currently only approved for treating cystic fibrosis, there are efforts to repurpose them for conditions with "acquired" CFTR dysfunction, for example, chronic obstructive pulmonary disease. In addition to targeting the primary lung pathology, CFTR therapeutics may possess value-added effects: their anti-inflammatory properties may dampen exaggerated immune cell responses and promote cerebrovascular dilation; the latter aspect may offer some protection against COVID-19 related stroke.

Keywords: brain; cerebrovascular; immune cells; lung; tumor necrosis factor.