Analysis of Differences in Lymphocyte Subsets and CD4+ T Cells Immune Activation Between Re-detectable Positive and Non-re-detectable Positive COVID-19 Convalescent Patients

Background: When coronavirus disease 2019 (COVID-19) first broke out, much literature was reported on the re-detectable positive phenomenon of COVID-19 patients during recovery; however, there were few studies on the lymphocyte subsets, T-lymphocyte activation indicators, and levels of specific antibodies between the re-detectable positive (RP) and non-re-detectable positive (NRP) patients. Objectives: This study aimed to analyze the immunological characteristics of RP and NRP patients among convalescent patients from post-discharge COVID-19 patients and to explore immunological factors related to RP. Methods: Anticoagulated whole blood samples were collected from 11 healthy controls (HCs) and 66 COVID-19 convalescent patients. Then, the percentage of lymphocyte subsets and CD4+CD38+/HLA-DR+ T cells were tested with flow cytometry, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike protein receptor-binding domain immunoglobulin G (S-RBD-IgG) antibody was detected by chemiluminescence. Results: B cells (%) in the RP group were significantly lower than that in the HC group (P = 0.014), and B cells (%) decreased successively in HC, NRP, and RP groups, with significant differences among the three groups (P = 0.016). CD3+ and CD8+ T cells (%) in the RP group were noticeably higher than that in the NRP group (P = 0.004 and 0.019, respectively); nevertheless, there was no difference in CD4+ T cells (%) and natural killer (NK) cells (%) among the three groups. The CD4+CD38+ and CD4+HLA-DR+ T cells (%) in the RP group were noticeably higher than that in the HC group (P = 0.013 and 0.025). The analysis of differences among the three groups showed that CD4+CD38+ and HLA-DR+ T cells (%) were also significantly different (P = 0.037 and 0.015), and CD4+HLA-DR+ T cells (%) in the three groups increased in turn. Meanwhile, there was a positive correlation between RBD-IgG titer and CD4+HLA-DR+ (%) (P = 0.003, r = 0.517), and the RBD-IgG titer of HLA-DR+ high group was higher than that of HLA-DR+ Low group (P = 0.005) in the COVID-19 convalescent patients. Conclusions: In this study, the immunological characteristics of the RP patients of COVID-19 convalescent patients were analyzed based on the lymphocyte subsets and the relationship between S-RBD-IgG and activated CD4+ T cells. The results showed that the low B cells (%) and the increased CD4+HLA-DR+ T cells (%) in the convalescent patients of COVID-19 might be related to the RP phenomenon, and the activated CD4+ T cells might play a crucial role in specific antibody responses.