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.

The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication

“…There was also increased concern for patients with CF, an inherited, autosomal recessive disorder caused by mutations in the gene encoding the anion channel Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that can lead to chronic pulmonary infections and respiratory failure. However, COVID-19 incidence estimates in CF were reported to be lower than in the general population with often less severe outcomes than originally anticipated 36,155,156 . In our experimental mouse model, we demonstrate that recent pulmonary infection with S. aureus resulted in significantly enhanced innate control of SCV2 replication.…”

“…While certain chronic lung diseases, including tuberculosis (TB) 28,29 and chronic obstructive pulmonary disease (COPD) [30][31][32][33] have been associated with increased severity of COVID-19 in most studies, other chronic pulmonary conditions, such as asthma [32][33][34][35] and cystic fibrosis (CF) [36][37][38] did not consistently correlate with worsened COVID-19 presentation and have even been associated with improved disease outcomes. The immunological factors in the lung that determine such variability in early viral control, and thus the likelihood of developing severe disease, are incompletely understood, and challenging to examine in clinical settings.…”

The Impact of Antimicrobial Resistance in Cystic Fibrosis

“…As previously described, CFTR impairment leads to a dysfunction of the environment of the respiratory tract. In recent years, new drug therapies aimed at correcting the underlying defect, modulators of the CFTR channel protein, have come onto the market, leading to a substantial clinical improvement in PwCF, modifying disease progression [ 64 , 65 ]. Evidence shows that restoration of CFTR channel protein function is associated with improved mucociliary clearance, and airway surface hydration, enhancing endogenous defence mechanisms by influencing the microbiology and response to bacterial infections in CF airways.…”

Occurrence of COVID-19 in cystic fibrosis patients: a review

“…ACE polymorphisms have additionally been related to COVID-19, as studies have indicated that patients with the ACE D/D polymorphism showcase advanced medical signs and symptoms and a higher danger of lung damage in comparison to people with I/I or D/I polymorphisms (Karakaş Çelik et al, 2021 ). Furthermore, studies have validated that ACE polymorphisms can affect ACE2 expression, leading to the CF phenotype and pulmonary inflammation associated with the development of COVID-19 (Vitiello et al, 2023 ). It is critical to highlight that the angiotensin-converting enzyme 2 (ACE2) serves as the crucial host receptor for SARS-CoV-2 entry via the spike (S) protein on the virus surface (Zhang et al, 2020 ).…”

“…To ensure proper follow-up, facilities reached out to individuals showing symptoms indicative of COVID-19. According to a recent publication (Tedbury et al, 2023 ), CFTR may additionally affect the severity of SARS-CoV-2 infection and COVID-19 ailments in CF patients (Vitiello et al, 2023 ). Meanwhile, a literature evaluation (Marques et al, 2023 ) emphasizes the restricted understanding regarding the effects of COVID-19 on CF patients.…”