Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16⁺ and IRF1-enriched CD14⁺ monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8⁺ T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染通常会导致严重的并发症甚至死亡。然而，也有无症状感染的报道，突出了个体免疫反应的差异。在这里，我们对从 COVID-19 康复者和健康供体中收集的外周血单核细胞进行了单细胞染色质可及性和 T 细胞受体分析。在从 COVID-19 康复的个体的先天性和适应性免疫细胞中观察到染色质重塑。与健康供体相比，恢复个体含有大量富含 TBET 的 CD16 ⁺和富含 IRF1 的 CD14 ⁺具有顺序训练和激活的表观基因组状态的单核细胞。康复个体中的 B 细胞谱系表现出从未成熟 B 细胞到产生抗体的浆细胞的加速发育程序。最后，对单细胞 T 细胞受体克隆性与染色质可及性景观的综合分析揭示了假定的 SARS-CoV-2 特异性 CD8 ⁺ T 细胞的扩张，其表观基因组特征可促进效应细胞或记忆细胞的分化。总体而言，我们的数据表明，从 COVID-19 康复的个体的免疫细胞表现出染色质可及性景观的全局重塑，表明免疫记忆的建立。