Immune responses to Coronavirus disease-19 with Thymosin α 1 intervention: an observational cohort study

Background Coronavirus disease-19 (COVID-19) pandemic has posed a serious threat to global health. Thymosin α 1 (Tα1) was considered being applied in COVID-19 therapy. However, there were limited clinical evidence to support. We aimed to study the immune and inflammation response to COVID-19 under Tα1 treatment and confirm its clinical benefit. Methods We did a cohort study including COVID-19 patients and healthy volunteers with or without Tα1 treatment. We obtained peripheral blood mononuclear cells (PBMCs) samples. Single cell RNA-sequencing (ScRNA-seq) and T cell receptor-sequencing (TCR-seq) was done to test for immune responses. Findings The proportion of CD3+KLRD1+ NKT, TBX21+CD8+ NKT was significant higher in Health controls with Tα1 treatment (HCT) than those without Tα1 (HC) (p=0.016; p=0.031). The proportion of CD3+KLRD1+ NKT, TBX21+CD8+ NKT was also observed increase in COVID-19 patients with Tα1 treatment (COVT) than those without Tα1 (COV) (p=0.024; p=0.010). The proportion of CD33-HLA-DMA-CD14+ classical monocyte was significant lower in COVT in comparison with COV. Those cell sets were significantly associated with thymosin intervention (CD3+KLRD1+ NKT, p=0.028; TBX21+CD8+ NKT, p=0.003; CD33-HLA-DMA-CD14+ classical monocyte, p=0.047). Interpretation The increased T cell and decreased monocyte response might support the prevention and therapy effect of Tα1 treatment. These data might also serve as a rich resource for designing cellular immunity therapies for this pandemic disease. 53 peripheral blood mono-nuclear cell (PBMC) samples including 42 COVID-19 patients derived samples and 11 healthy controls (HCs) derived samples