Due to their pre-existing pulmonary disease, pwCF may be considered at high risk of developing severe symptoms of COVID-19 [42]; however, the data from Lotti and co-workers [34] together with some epidemiological studies [42,43,44] indicated a counterintuitive situation: CFTR protein can play a major role in the regulation of SARS-CoV-2 replication machinery upon its entry into the host cell, possibly due to ionic dysregulation caused by CFTR loss of function. This evidence concerns the gene CFTR and COVID-19.