CFTR alleles associated with mild or severe COVID-19. LASSO logistic regression analysis on the boolean representation of ultra-rare variants (the presence of at least two variants, al2), (A) and rare variants (the presence of at least two variants, al2), (B) of all autosomal genes (see Fallerini et al. 2022 for complete representations). The upward histograms (positive weights) represent the features associated with severe COVID-19, whereas the downward histograms (negative weights) represent the features associated with mild COVID-19. (A) The presence of at least two, in cis or trans, CFTR ultra-rare loss-of-function variants was picked up as one of the most important features associated with COVID-19 severity. The loss-of-function variants were defined on the basis of a residual global CFTR activity reduction between 50–79%. (B). The gain-of-function CFTR complex allele [G576V;R668C] was picked up as one of the most important features associated with COVID-19 mildness.