SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation

As an inherited disorder characterized by severe pulmonary disease, cystic
fibrosis could be considered a comorbidity for coronavirus disease 2019.
Instead, current clinical evidence seems to be heading in the opposite direc-
tion. To clarify whether host factors expressed by the Cystic Fibrosis epithelia
may influence coronavirus disease 2019 progression, here we describe the
expression of SARS-CoV-2 receptors in primary airway epithelial cells. We show
that angiotensin converting enzyme 2 (ACE2) expression and localization are
regulated by Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
channel. Consistently, our results indicate that dysfunctional CFTR channels
alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral entry
and replication in Cystic Fibrosis cells. Depending on the pattern of ACE2
expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin
6 in healthy donor-derived primary airway epithelial cells, but a very weak
response in primary Cystic Fibrosis cells. Collectively, these data support that
Cystic Fibrosis condition may be at least partially protecting from SARS-CoV-2
infection.