Severe COVID-19 in Hospitalized Carriers of Single CFTR Pathogenic Variants
Margherita Baldassarri, Francesca Fava, Chiara Fallerini, Sergio Daga, Elisa Benetti, Kristina Zguro, Sara Amitrano, Floriana Valentino, Gabriella Doddato, Annarita Giliberti, Laura Di Sarno, Maria Palmieri, Miriam Lucia Carriero, Diana Alaverdian, Giada Beligni, Nicola Iuso, Francesco Castelli, Eugenia Quirós-Roldán, Mario U. Mondelli, Rosalba Miceli, Elisa Frullanti, Simone Furini, Francesca Mari, Alessandra Renieri, Chiara Gabbi
Abstract
The clinical presentation of COVID-19 is extremely heterogeneous, ranging from asymptomatic to severely ill patients. Thus, host genetic factors may be involved in determining disease presentation and progression. Given that carriers of single cystic fibrosis (CF)-causing variants of the CFTR gene—CF-carriers—are more susceptible to respiratory tract infections, our aim was to determine their likelihood of undergoing severe COVID-19. We implemented a cohort study of 874 individuals diagnosed with COVID-19, during the first pandemic wave in Italy. Whole exome sequencing was performed and validated CF-causing variants were identified. Forty subjects (16 females and 24 males) were found to be CF-carriers. Among mechanically ventilated patients, CF-carriers were more represented (8.7%) and they were significantly (p < 0.05) younger (mean age 51 years) compared to noncarriers (mean age 61.42 years). Furthermore, in the whole cohort, the age of male CF-carriers was lower, compared to noncarriers (p < 0.05). CF-carriers had a relative risk of presenting an abnormal inflammatory response (CRP ≥ 20 mg/dL) of 1.69 (p < 0.05) and their hazard ratio of death at day 14 was 3.10 (p < 0.05) in a multivariate regression model, adjusted for age, sex and comorbidities. In conclusion, CF-carriers are more susceptible to the severe form of COVID-19, showing also higher risk of 14-day death.