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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE169441 | GEO | 2022/06/08

REPOSITORIES: GEO

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Project description:The clinical presentations and outcomes of SARS-CoV-2 infection are highly variable, ranging from asymptomatic infections to severe conditions, and the underlying mechanisms remain largely unknown. In this study, we performed the single-cell RNA sequencing to examine the profiles of the peripheral blood mononuclear cells (PBMCs) from the healthy controls (HC), asymptomatic individuals (AS) and symptomatic COVID-19 patients (SM) with various clinical features and disease severity. We first identified nine major cell types, including T cells, B cells, monocytes, natural killer (NK) cells, dendritic cells (DC), platelets, neutrophils, plasma cells and stem cells from a total of 119,799 single cells captured and filtered for the final analysis, and then divided these cell types into separate cell clusters and sub-clusters, respectively. We revealed that SARS-CoV-2 infection resulted in profound alternations in various cellular compartments and identified a number of distinct immune cell subsets that were associated with various clinical presentations, disease severity and viral persistence of COVID-19. (NCAM1+CD160+) NK cells increased significantly in AS and SM individuals compared with the HC. SM patients showed a significant increase in (LAG3+CD160+CD8+) NKT cells and a decrease in (CD4-CD8-) double negative T cells compared with the AS subjects. (CD68-CSF1R-IL1BhiCD14+) classical monocytes were significantly higher in patients with severe disease (SD) than the patients with moderate disease (MD). (CD68-CSF1R-IL1BhiCD14+) classical monocytes and (CLEC10A-S100A9lo)pDC were positively and negatively correlated with the age-related disease severity of COVID-19 patients, respectively. Increases in (CD33-HLA-DMA-CD14+) classical monocytes and (CLEC10A-S100A9lo)pDC were associated with long-term nucleic acid test positive (LTNP) patients compared with the short-term nucleic acid test positive (STNP) individuals. Increases in (LAG3+CD160+CD8+) NKTcells and (FOXP3+IL2RA+IL7R+CD4+) Treg cells were observed in a patient lacking B cells and plasma cells. Dramatic increases in neutrophils, (CD33-HLA-DMA-CD14+) classical monocytes, and (CD68-CSF1R-IL1BhiCD14+) classical monocytes were detected at a later stage of a fatal patient. Our findings may enhance our understanding of the immune cell alternations involved in the pathogenesis of COVID-19 and the protective immune responses against SARS-CoV-2 infection.

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

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