Distinct airway immune cell constitution in persistent post COVID-19 ILD.

Pulmonary sequelae occur in survivors of COVID-19, but the mechanisms involved are incompletely understood. Importantly, the majority of patients, despite presenting with extensive ILD for months following COVID-19, make a full recovery, while in others ILD persists. We characterized the alveolar immune cell compartment from bronchoalveolar lavage in a small group of patients presenting with lung abnormalities 6 months post SARS-CoV-2 infection. After a year’s follow-up, patients showed either persistence of ILD with fibrotic-like lesions (n=6) or resolution (n=12) of lung lesions and were grouped accordingly. Additionally, 6 patients with preexisting ILD underwent bronchoscopy post-COVID-19 and were evaluated in parallel. BAL cell RNA-seq analysis revealed enriched neutrophil/monocyte chemotaxis pathways in patients with persistent fibrotic-like abnormalities and increased monocyte infiltration of the airways. In contrast, a signature of T-cell activation was prominent upon resolution. Fibrotic markers in macrophages, such as SPP1 and Col1a1, as well as pro-inflammatory cytokines, such as IL1b and TNF, were higher in the fibrotic group. In contrast, genes involved in antigen presentation and T cell activation, such as CCR7, CD40L, IFNγ, and antiviral responses such as IFNλ were upregulated in the resolver group. Interestingly, macrophages from the fibrotic group also showed increased ATP production from glycolysis, in agreement with a pro-inflammatory immunometabolic phenotype. Our results point to a distinct airway immune cell composition related to fibrosis development following lung injury and constitute potential early markers of fibrotic ILD.