Immunological profiling of COVID-19 patients with pulmonary sequelae

Abstract

ABSTRACTCellular immunity may be involved in organ damage and rehabilitation in patients with coronavirus disease 2019 (COVID-19). We aimed to delineate immunological features of COVID-19 patients with pulmonary sequelae (PS) one year after discharge. 50 COVID-19 survivors were recruited and classified according to radiological characteristics: 24 patients with PS and 26 patients without PS. Phenotypic and functional characteristics of immune cells were evaluated by multiparametric flow cytometry. Patients with PS had an increased proportion of natural killer (NK) cells and lower percentage of B cells compared to patients without PS. Phenotypic and functional features of T cells in patients with PS were predominated by the accumulation of CD4+ T cells secreting IL-17A, short-lived effector-like CD8+ T cells (CD27-CD62L-) and senescent T cells with excessive secretion of granzyme-B/perforin/IFN-γ. NK cells were characterized by the excessive secretion of granzyme-B and perforin and the downregulation of NKP30 and NKP46; highly activated NKT and γδ T cells exhibited NKP30 and TIM-3 upregulation and NKB1 downregulation in patients with PS. However, immunosuppressive cells were comparable between the two groups. The interrelation of immune cells in COVID-19 was intrinsically identified, whereby T cells secreting IL-2, IL-4 and IL-17A were enriched among CD28+ and CD57-cells and cells secreting perforin/granzyme-B/IFN-γ/TNF-α expressed markers of terminal differentiation. CD57+NK cells, CD4+perforin+ T cells and CD8+CD27+CD62L+ T cells were identified as the independent predictors for residual lesions. Overall, our findings unveil the profound imbalance of immune landscape that may correlate with organ damage and rehabilitation in COVID-19.IMPORTANCEA considerable proportion of COVID-19 survivors have residual lung lesions, such as ground glass opacity and fiber streak shadow. To determine the relationship between host immunity and residual lung lesions, we performed an extensive analysis of immune responses in convalescent patients with COVID-19 one year after discharge. We found significant differences in immunological characteristics between patients with pulmonary sequelae and patients without pulmonary sequelae one year after discharge. Our study highlights the profound imbalance of immune landscape in the COVID-19 patients with pulmonary sequelae, characterized by the robust activation of cytotoxic T cells, NK cells and γδ T cells as well as the deficiencies of immunosuppressive cells. Importantly, CD57+NK cells, CD4+perforin+ T cells and CD8+CD27+CD62L+ T cells were identified as the independent predictors for residual lesions.