Immunological similarities between post-COVID19 lung sequelae and idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown cause. An emerging clinical entity post-COVID is pulmonary fibrosis (PCPF), that share many immunological features with IPF. The aim of the present study was to analyse the similarity and differences of CD4, CD8 and NK cells and the expression of immune-checkpoint (IC) PD-1 and TIGIT in the peripheral blood of patients affected by fibrotic disease, compared with sarcoidosis patients and healthy controls. Patients followed at the rare pulmonary disease centre of the University of Siena were enrolled. Peripheral blood samples were collected, and stained with monoclonal antibodies CD4, CD8, NK cells, PD-1 and TIGIT through flow cytometric. The results showed a depletion of CD4 and NK cells in IPF patients than other groups (p=0.003), in contrast with CD8 cells (p<001). Correlation analysis demonstrated an indirect correlation between CD4 and CD8 cells in IPF and sarcoidosis patients (p<0.001 =-0.87 and p= 0.042; r=-0.6, respectively). Conversely, PCPF patients revealed a direct correlation between CD4 and CD8 cells (p<0.001; r=0.90) accentuating an immune response restoring. The expression of PD-1 and TIGIT was abundant on T and NK cell subsets of the two lung fibrotic groups. The co-expression of PD-1 and TIGIT on the surface of CD4 and CD8 were increased in such diseases. We observed a significant imbalance not only of CD4, CD8 and NK blood percentages in IPF and PCPF patients but also in their functional phenotypes evaluated through the expression of IC.