Dynamic Characteristics of Lymphocyte Subsets and Their Predictive Value for Disease Progression and Prognosis in Primary Infection and Unvaccinated COVID-19 Patients

Xinyi Zhang,1,2,&ast; Zhu Chen,3,&ast; Jun Zheng,4 Chen Feng,5 Bennan Zhao,1 Lijuan Lan,1 Dafeng Liu1 1The First Ward of Internal Medicine, Public Health Clinical Centre of Chengdu, Chengdu, People’s Republic of China; 2Department of Endocrinology & Metabolism, Sichuan University West China Hospital, Chengdu, People’s Republic of China; 3Department of Drug Clinical Trial Center, Public Health Clinical Centre of Chengdu, Chengdu, People’s Republic of China; 4Medical Department, Public Health Clinical Centre of Chengdu, Chengdu, People’s Republic of China; 5Legal Services Division, Public Health Clinical Centre of Chengdu, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dafeng Liu, The First Ward of Internal Medicine, Public Health Clinical Centre of Chengdu, No. 377 Jingming Road, Jinjiang District, Chengdu, Sichuan, 610066, People’s Republic of China, Email [email protected]: Our cohort study aimed to investigate the dynamic changes of lymphocyte subsets and their abilities to predict disease severity and prognosis in primary infection and unvaccinated COVID-19 patients.Methods: A total of 773 cases, including 718 primary infection and unvaccinated COVID-19 patients and 55 controls. COVID-19 patients were assigned to severe and nonsevere groups according to disease severity, as well as survival and death groups according to prognosis. Serum samples were collected to measure the numbers of total lymphocytes and lymphocyte subsets. The differences among different severity groups were analyzed. Spearman correlation was performed to assess associations between lymphocyte subsets and disease severity and prognosis. Meanwhile, receiver operating characteristic (ROC) curves were also analyzed to find optimal cutoff points.Results: At admission, the severe group demonstrated significantly lower total lymphocyte counts and percentages, CD3+ and CD3+CD4+ T cell counts and percentages, CD3+CD8+ T cell counts, CD19+ B cell counts and CD56+ NK cell counts and percentages than the nonsevere group. Meanwhile, compared with the survival group, the death group also had lower total lymphocyte counts and percentages, CD3+, CD3+CD4+ and CD3+CD8+ T cell counts. Additionally, differences in these parameters were also noticed within four weeks after admission. Furthermore, Spearman analysis reported that disease severity was negatively correlated with lymphocyte counts and percentages, CD3+, CD3+CD4+ and CD3+CD8+ T cell counts, CD3+ and CD3+CD4+ T cell percentages (r=− 0.166, − 0.179, − 0.173, − 0.186, − 0.127, − 0.117, − 0.149, respectively)(all P< 0.05). The prognosis of death was also negatively correlated with total lymphocyte counts and percentages, CD3+, CD3+CD4+ and CD3+CD8+ T cell counts (r=− 0.125, − 0.121, − 0.123, − 0.123, − 0.091, respectively)(all P< 0.05).Conclusion: In primary infection and unvaccinated COVID-19 patients total lymphocytes and T cell, B cell and NK cell subsets at COVID-19 onset play valuable roles in predicting disease severity and prognosis.Clinical Trial Registry: Chinese Clinical Trial Register ChiCTR2000034563.Keywords: lymphocyte subsets, coronavirus disease 2019, COVID-19, prediction, severity, prognosis