CD4+ T cells
Lymphopenia is one of the predominant phenotypes in COVID-19 patients [25-27], which is further evidenced by scRNA–seq analysis revealing a reduction in total and subsets of CD4+ T cells after SARS-CoV-2 infection [28, 29]. Both naive and Th1 CD4+ T cells were reduced, especially in severe patients [23, 30], which might be correlated with the less expression of TBX21 and the lower TBX21 locus accessibility by integrates analysis of the single-cell assay for transposase accessible chromatin (ATAC)-seq and scRNA-seq [30]. The elevated expression of gene sets in metabolic and apoptotic pathways of CD4+ T cells contributed to T cell lymphopenia [29]. However, Wauters et al performed single-cell deep immune profiling of bronchoalveolar lavage samples and found that CD4+Th1-like-cells expressing TBX21 and RUNX3 were increased in critical COVID-19 patients compared to mild COVID-19 patients [31]. Moreover, the ZFP36 , which was reported to restrain T cell expansion and effector functions [32] was downregulated in moderate and severe recovery patients and might be associated with Th1 proportion recovery [33]. To dissect the exact roles of CD4+T cells, a better understanding of their subsets and status in COVID-19 patients is needed.