Background: Genotype-phenotype associations allow to understand clinical variability in primary ciliary dyskinesia (PCD). We studied whether clinical characteristics and reported symptoms differ by genotypes using data from COVID-PCD, a large international participatory study.

Method: A baseline questionnaire assessed genetic test results, clinical history and current symptoms. We tested differences between functional gene groups categorized into dynein structure (DS), dynein assembly (DA), nexin-dynein regulatory complex (N-DRC) and radial spoke/central complex (CC).

Results: Among 738 COVID-PCD participants, 213 (29%) reported their genetic mutation (median age 18 yrs [range 1-66]; 59% female). The largest gene group was DS (n=125;60%) followed by CC (n=37;18%), DA (n=25;12%) and N-DRC (n=20;10%). Age at diagnosis was lowest for the DA group (5 yrs, IQR 1-9) and highest for CC (11 yrs, IQR 2-37). Laterality defect ranged from 38-62% except for the CC group where 1 (5%) reported laterality defect (p=0.001). Congenital heart disease was reported most often in the N-DRC group (n=8;23%) and least often in the DS group (n=8;7%) (p=0.052). Participants in all genotypes reported frequent symptoms - daily cough ranged from 68% in DA to 75% in CC (p=0.937); ear pain past 3 months from 58% in DA to 63% in CC (p=0.967), and shortness of breath from 46% in DA to 63% in N-DRC (p=0.442). Low FEV1 (<50% pred) was more frequent in the N-DRC group (n=5;23%) than in the DA group (n=6;8%).

Conclusion: Our results confirm typical differences in laterality defects and lung function between genotypes, but current symptoms were reported frequently in all genotypes.

Funding: SNSF 320030B_192804, SLA 2021-08_Pedersen. A BEAT-PCD collaboration.