(534) Covid-19 in cystic fibrosis patients compared to the general population: severity and virus-host cell interactions

Background: People with cystic fibrosis (pwCF) may be at risk of severe COVID-19. A multicenter prospective study (COVID-2020-12371781, supported by the Italian Ministry of Health) was designed to compare the severity of COVID-19 and virus-host cell interactions, in term of gene expression, between pwCF and people from the general population (GP).

Methods: We enrolled pwCF and individuals from the GP, with or without COVID-like symptoms, who underwent nasopharyngeal swab test with real time polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2. COVID-19 severity was defined by 1) hospitalization or 2) requirement or increased need of oxygen therapy. Multiple logistic regression models adjusted by age and number of comorbidities were used to compare the risk of severe COVID-19 between groups. Differences in gene expression between pwCF and GP, positive and negative to RT-PCR, were evaluated by RNA sequencing on nasopharyngeal swabs collected at the time of enrollment. After pre-processing, edgeR was used to perform differential expression analysis between pwCF and individuals from the GP. Gene expression differences with a false discovery rate less than 0.05 were considered significant.

Results: We enrolled a total of 194 pwCF (32 positive and 162 negative, median age: 22, range: 1 m-66 y) and 391 subjects from the GP (152 positive and 239 negative, median age: 15, range: 1 m-69 y). Ten pwCF (31.3%) and 57 individuals from the GP (40.4%) required hospitalization (adjusted OR: 0.46, 95% CI: 0.19-1.14). The proportion of subjects requiring supplemental oxygen therapy was lower in pwCF (9.4%, n=3) than in the GP (24.8%, n=35) (adjusted OR: 0.14, 95% CI: 0.03-0.70). Two individuals from the GP required admission to intensive care unit (ICU) and 2 subjects died, while no ICU admission or death were reported among pwCF. In all pwCF, both positive and negative for SARS-CoV-2, we found a significantly lower expression of genes, particularly of the “ribosome” and “Coronavirus disease” patterns, as compared to the GP.

Conclusions: COVID-19 does not seem to be more severe in pwCF as compared to the GP, likely due to closer follow up, rigorous use of preventive measures and possibly to intrinsic factors of this population. Our preliminary results indicate reduced expression of ribosomal genes in pwCF compared with the GP, regardless of SARS-CoV-2 infection status. This observation suggests that the protein translation machinery is impaired in pwCF and may be relevant to the onset of SARS-CoV-2 infection, creating an unfavorable environment for viral replication.

Acknowledgements:

References: