Background:Approximately 10% of patients hospitalised with COVID-19 have residual lung abnormalities (RLAs) at 12 months. In clinical practice, CT scan appearances are often used to guide management. Whether such radiological changes reliably reflect immunopathomechanisms, and can therefore inform the treatment approach, is unclear and an important clinical question. 

Methods: We compared the single cell transcriptomic and T cell receptor (TCR) profiles of bronchoalveolar lavage cells from patients with Post-COVID RLAs with either predominantly inflammatory or fibrotic radiological appearances.

Results: We generated a dataset of 55, 776 cells. CD4 central memory T cells (TCM) and CD8 effector memory T cells (TEM) were significantly increased in the inflammatory sub-phenotype. Both patient groups were transcriptionally similar and exhibited clonal expansion and high TCR clustering, without enrichment for SARS-CoV-2 reactive sequences.

Conclusions: We describe the first comparison of purported radiological subphenotypes in patients with Post-COVID RLAs, which may actually represent different manifestations of the same disease. Antigen-specific immune responses to unidentified T cell targets, imply a breach of immune tolerance in the lung and a potential role for T-cell directed therapies in these patients, agonistic of radiological appearance.