Cytoimmunological Profile of Lower Airways in Post-COVID-19 Syndrome (PCS): Predictive Value of Bronchoalveolar Lavage

Background. It has yet to be determined whether the immunocytological profile of the bronchoalveolar lavage (BAL) in respiratory post-COVID syndrome (PCS) may reflect the risk of persistent interstitial lung disease (ILD), including pulmonary fibrosis. We aimed to assess the prognostic value of BAL cytoimmunologic profile in PCS-related ILD. Material & Methods. We enrolled 58 non-smoking patients with COVID-19 history, having new-onset ILD, divided into PCS remission and PCS persistence groups, based on clinical data including repeated computed tomography and pulmonary function tests. We phenotyped BAL major T cell subsets, immune checkpoints (including programmed cell death-1, PD1) and markers of Th1/Th2/Th17 polarization. Results. PCS compared to controls showed increased total cell, lymphocyte and neutrophil count and high BAL neutrophil:lymphocyte ratio (NLR). PCS persistence compared to controls presented increased neutrophil count (26[17-36] vs. 2.6[1.9-5.4] 103/ml, median[Q1-Q3], p<0.001) and percentage, BAL NLR (0.77[0.26-1.63] vs. 0.21[0.17-0.31], p<0.0001), CD8+PD1+ cell percentage (43.5 [34-60.5] vs. 24.5[22-44]%, p=0.045), decreased CD4:CD8 ratio. High percentage of CD4+CD196+CD183- cells (relevant to Th17 activity, 6.2[2.0-9.4] vs 1.2[0.7-2.7]%, p=0.02), and increased BAL supernatant elevated IL-8 levels (62.5[16-243] vs. 10.9[3.44-32]pg/mL, p=0.002) were found in PCS persistence vs. controls. In total PCS, predicted values of Vital Capacity (VC) and Diffusing Lung Capacity for CO (DLCO) correlated negatively with BAL NLR, VC correlated negatively with BAL CD8+PD1+; DLCO correlated positively with CD4:CD8 ratio. Conslusions. Worse prognosis in PCS is associated with higher BAL NLR, BAL neutrophilia, elevated percentage of CD8+PD1+ lymphocytes, decline in CD4:CD8 ratio. Th17 cells and IL-8 participate in lung PCS persistence.