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

Background Coronavirus disease-19 (COVID-19) pandemic has posed a serious threat to global health. Thymosin a 1 (Ta1) 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 Ta1 treatment and confirm its clinical benefit. Methods We did a cohort study including COVID-19 patients and healthy volunteers with or without Ta1 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 Ta1 treatment (HCT) than those without Ta1 (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 Ta1 treatment (COVT) than those without Ta1 (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 Ta1 treatment. These data might also serve as a rich resource for designing cellular immunity therapies for this pandemic disease. Overall design: 53 peripheral blood mono-nuclear cell (PBMC) samples including 42 COVID-19 patients derived samples and 11 healthy controls (HCs) derived samples

研究背景：新型冠状病毒肺炎（Coronavirus disease-19, COVID-19）大流行对全球公共卫生构成严重威胁。胸腺素α1（Thymosin α1, Ta1）曾被考虑用于新型冠状病毒肺炎的治疗，但相关临床支持证据十分有限。本研究旨在探讨Ta1治疗过程中机体针对新型冠状病毒肺炎的免疫与炎症应答，并验证其临床获益。
研究方法：本研究为队列研究，纳入接受或未接受Ta1治疗的新型冠状病毒肺炎患者与健康志愿者，采集外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）样本。采用单细胞RNA测序（single cell RNA-sequencing, scRNA-seq）与T细胞受体测序（T cell receptor-sequencing, TCR-seq）检测机体免疫应答情况。
研究结果：接受Ta1治疗的健康对照组（Health controls with Ta1 treatment, HCT）中CD3+KLRD1+自然杀伤T细胞（Natural Killer T, NKT）、TBX21+CD8+自然杀伤T细胞的比例显著高于未接受治疗的健康对照组（HC）（p=0.016；p=0.031）。接受Ta1治疗的新型冠状病毒肺炎患者组（COVID-19 patients with Ta1 treatment, COVT）中上述两种细胞的比例同样显著高于未接受治疗的患者组（COVID-19 patients without Ta1 treatment, COV）（p=0.024；p=0.010）。COVT组中CD33-HLA-DMA-CD14+经典单核细胞的比例显著低于COV组。上述细胞群与胸腺素干预存在显著关联（CD3+KLRD1+ NKT：p=0.028；TBX21+CD8+ NKT：p=0.003；CD33-HLA-DMA-CD14+经典单核细胞：p=0.047）。
研究结论：T细胞应答增强与单核细胞应答减弱可为Ta1治疗的预防与治疗效果提供支撑，本研究数据亦可作为该大流行疾病细胞免疫治疗方案开发的宝贵资源。
整体实验设计：共采集53例外周血单个核细胞（PBMC）样本，其中42例来自新型冠状病毒肺炎患者，11例来自健康对照者（HCs）。