The impact of SARS-CoV-2 infection in patients with cystic fibrosis undergoing CFTR channel modulators treatment: a literature review

Abstract Several risk factors for Coronavirus-2019 (COVID-19) disease have been highlighted in clinical evidence. Among the various risk factors are advanced age, metabolic illness such as diabetes, heart disease, and diseases of the respiratory system. Cystic Fibrosis (CF) is a rare disease with autosomal recessive transmission, characterised by a lack of synthesis of the CFTR channel protein, and multi-organ clinical symptoms mainly affecting the respiratory tract with recurrent pulmonary exacerbations. In view of the pathophysiological mechanisms, CF disease should be in theory considered a risk factor for SARS-CoV2 or severe COVID-19. However, recent clinical evidence seems to point in the opposite direction, suggesting that CF could be a protective factor against severe COVID-19. Possibly, the lack of presence or function of the CFTR channel protein could be linked to the expression of the membrane glycoprotein ACE-2, a key enzyme for the endocellular penetration of SARS-CoV-2 and related to the pathophysiology of COVID-19 disease. Furthermore, CFTR channel modulating agents could indirectly influence the expression of ACE-2, playing an important role in restoring the proper functioning of mucociliary clearance and the pulmonary microbiome in the host response to SARS-CoV-2 infection. In this review, the authors attempt to shed light on these important associations of issues that are not yet fully elucidated.