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Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
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SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation

Valentino Bezzerri1,2, Valentina Gentili3, Martina Api4

  • 1Cystic Fibrosis Center of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Nature Communications
|January 10, 2023
PubMed

Insights

Cystic Fibrosis (CF) may protect against COVID-19. Research shows CFTR dysfunction reduces SARS-CoV-2 entry and replication in airway cells, potentially lowering infection severity.

Area of Science:

  • Pulmonary Medicine
  • Virology
  • Genetics

Background:

  • Cystic Fibrosis (CF) is an inherited disorder causing severe lung disease.
  • CF was anticipated to be a COVID-19 comorbidity, but clinical data suggest otherwise.
  • Investigating host factors in CF epithelia influencing COVID-19 progression is crucial.

Purpose of the Study:

  • To determine if host factors in Cystic Fibrosis epithelia affect COVID-19 progression.
  • To analyze the expression of SARS-CoV-2 receptors in primary airway epithelial cells from CF patients.

Main Methods:

  • Examined angiotensin converting enzyme 2 (ACE2) expression and localization in primary airway epithelial cells.
  • Assessed the impact of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel function on ACE2 regulation.
  • Measured SARS-CoV-2 entry, replication, and Interleukin 6 response in CF and healthy cells.

Main Results:

  • ACE2 expression and localization are regulated by the CFTR channel.
  • Dysfunctional CFTR channels in CF cells reduce SARS-CoV-2 entry and replication.
  • SARS-CoV-2 spike protein induced significantly lower Interleukin 6 levels in CF cells compared to healthy cells.

Conclusions:

  • Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction alters susceptibility to SARS-CoV-2.
  • CF cells exhibit reduced viral entry and replication, suggesting partial protection from COVID-19.
  • The findings indicate that Cystic Fibrosis may offer a degree of protection against SARS-CoV-2 infection.

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