- Published
- 21 November 2023
- Journal article
Long-term effects of SARS-CoV-2 on ciliogenesis through altered expression of FOXJ1
- Authors
- Source
- Thorax
Abstract
Introduction Cilia are critically important in the mucociliary clearance of the airways. This study explores the long-term effects of SARS-CoV-2 on cilial function and regeneration.
Aim We aimed to investigate respiratory epithelial recovery and cilial function in individuals 3–12 months post SARS-CoV-2 infection.
Methods We studied 3 cohorts of patients: the first cohort (FOLLOW n=41) underwent nasal epithelial cell sampling 3–12 months after the first waves of SARS-CoV-2 infection in both hospitalised and community settings; the second cohort, (ULTRON n=10), 3–12 months post-Omicron variant infection in vaccinated individuals; the third cohort (PROSAIC n=46) had RNA extracted from nasal brushings 6–12 months after recovery from severe infection with pre-Omicron variants of SARS-CoV-2. In the first two cohorts, cilial function was assessed using high-speed-video-microscopy, with ultrastructural analysis assessed by Transmission Electron Microscopy. Expression of the ciliogenesis gene, FOXJ1, was measured by qRT-PCR in the third cohort.
Results In the initial FOLLOW cohort, there was significant loss of ciliation compared to controls. 90% of individuals had ultrastructural defects marked by mislocalised basal bodies and intracytoplasmic cilia up to 12 months post infection. There was no correlation with any ongoing nasal symptoms or symptoms of long COVID. In contrast, ciliogenesis was normal in the Omicron infected, vaccinated cohort, and no mislocalised basal bodies or intracytoplasmic cilia were seen. Defects in cilia function were present in both cohorts compared to pre-pandemic controls: reduced cilia beat frequency (FOLLOW p<0.01), reduced amplitude per second in both: (FOLLOW p<0.01, ULTRON p<0.01).
This ciliogenesis defect led us to explore FOXJ1 expression post-COVID: qRT-PCR showed a significant reduction of FOXJ1 mRNA levels 6 months (p<0.001) and 12 months (p=0.002) following pre-Omicron variant infections compared with healthy volunteers; however, there was a significant improvement between 6-months and 12-months.
Conclusion Cilia loss and defective ciliogenesis linked to reduced FOXJ1 expression persisted for a year following infection with early SARS-CoV-2 variants. No such defects were seen in vaccinated individuals infected with the Omicron variant despite some functional ciliary defects. This work illuminates novel long-term effects of viral infection on human epithelial function through altered expression of a key cilial regulator gene.
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Cite as
Stewart, I., Rai, R., Katsoulis, O., Bottier, M., Burgoyne, T., Cant, E., Shuttleworth, M., Crichton, M., Pinto, A., Hogg, C., Shah, A., Singanayagam, A., Chalmers, J., Shoemark, A. & Connell, D. 2023, 'Long-term effects of SARS-CoV-2 on ciliogenesis through altered expression of FOXJ1', Thorax, 78(S4), pp. A60-A61. https://doi.org/10.1136/thorax-2023-BTSabstracts.89