RESUMEN
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.
RESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its clinical manifestation (COVID-19; coronavirus disease 2019) have caused a worldwide health crisis. Disruption of epithelial and endothelial barriers is a key clinical turning point that differentiates patients who are likely to develop severe COVID-19 outcomes: it marks a significant escalation in respiratory symptoms, loss of viral containment and a progression toward multi-organ dysfunction. These barrier mechanisms are independently compromised by known COVID-19 risk factors, including diabetes, obesity and aging: thus, a synergism between these underlying conditions and SARS-CoV-2 mechanisms may explain why these risk factors correlate with more severe outcomes. This review examines the key cellular mechanisms that SARS-CoV-2 and its underlying risk factors utilize to disrupt barrier function. As an outlook, we propose that glucagon-like peptide 1 (GLP-1) may be a therapeutic intervention that can slow COVID-19 progression and improve clinical outcome following SARS-CoV-2 infection. GLP-1 signaling activates barrier-promoting processes that directly oppose the pro-inflammatory mechanisms commandeered by SARS-CoV-2 and its underlying risk factors.