P136 Relationship between cystic fibrosis disease severity and susceptibility to COVID-19 infection

Abstract

Objective: Since cytokine storm and hyperinflammation play a key role on CF disease severity, severe CF patients should be considered to have an increased risk of developing severe symptoms of COVID-19. In this preliminary study, we evaluated whether there was a relationship between clinical severity of CF siblings and their susceptibility to COVID-19 infection. Method: In our preliminary study, we used a targeted transcriptomic approach (CF Profiler Array) obtained from nasal samples of three families who had CF siblings harbouring same mutation but showing different severity of CF phenotype. The siblings were classified as severe or mild CF according to recurrent lung infection, hepatic involvement, and FEV1. Results: In severe CF patients (n = 4) compared to mild patients (n = 3) CXCL1 (FC:-3.53), CXCL2 (FC:-2,16), CXCL8 (FC:-5.41), IL1B (FC:-2.61), SERPINA1 (FC:-2.54), TNFSF10 (FC:-1.73) were found to be downregulated. CXCL1, CXCL2, CXCL8 play critical role during infection control in neutrophiles that release other chemotactic mediators and recruit leukocytes. Additionally IL1B and TNFSF10 also affect activation of leukocytes. In the case of COVID-19 infection, the expression of these genes increases and leads to a cytokine storm. However our results show that CXCL1, CXCL2, CXCL8, IL1B genes which have a function in IL-17, NFKB, NLRP3 signaling pathways are downregulated in severe CF patients. Significant evidence supports the role of IL-1B, NLRP3-dependent inflammasome activation which is a central mediator of severe COVID-19 in the pathogenesis of acute lung injury. However, downregulation of inflammatory pathways is detected in severe forms of CF. Conclusion: The results of our preliminary study strengthens the hypothesis that severe forms of CF may constitute an advantage to mild forms of CF in susceptibility to COVID-19 and CXC inhibitors may be a promising therapeutic option for COVID-19 in the future. Further analyses should be performed with larger sample sizes.