Hoffmann Andrew D, Weinberg Sam E, Swaminathan Suchitra, Chaudhuri Shuvam, Mubarak Hannah Faisal, Schipma Matthew J, Mao Chengsheng, Wang Xinkun, El-Shennawy Lamiaa, Dashzeveg Nurmaa K, Wei Juncheng, Mehl Paul J, Shihadah Laura J, Wai Ching Man, Ostiguin Carolina, Jia Yuzhi, D'Amico Paolo, Wang Neale R, Luo Yuan, Demonbreun Alexis R, Ison Michael G, Liu Huiping, Fang Deyu
bioRxiv. 2022 Mar 28:2022.03.26.485922. doi: 10.1101/2022.03.26.485922.
Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized multi-omic single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including covenlesent COVID-19 and sero-negative controls. The reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells are significantly associated with the patients recovered from severe COVID-19. Consistently, sc-RNA seq analysis reveals seven heterogeneous clusters of monocytes (M0-M6) and ten Treg clusters (T0-T9) featuring distinct molecular signatures and associated with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocyte and Treg expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters with S100 family genes: S100A8 & A9 with high HLA-I whereas S100A4 & A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, and a unique TGF-β high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-ived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (>= 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.
在新冠疫情爆发两年多来，人们对新冠病毒（SARS-CoV-2）活跃疾病期的人体免疫反应进行了广泛研究。然而，康复后的长期影响在很大程度上仍不为人知，而这对于深化我们对SARS-CoV-2以及新冠病毒相关长期并发症的理解至关重要。在此，我们对100名患者外周血中循环免疫细胞的多组学单细胞图谱进行了表征，包括新冠康复患者和血清阴性对照。短期单核细胞和长期调节性T（Treg）细胞频率的降低都与重症新冠康复患者显著相关。一致地，单细胞RNA测序分析揭示了单核细胞的七个异质性簇（M0-M6）和十个Treg簇（T0-T9），它们具有不同的分子特征，并与新冠严重程度相关。无症状患者含有表达高CD74或干扰素反应基因的最丰富的单核细胞和Treg簇。相比之下，重症康复患者显示出两个主要的炎症单核细胞簇，一个是具有高HLA-I的S100A8和A9的S100家族基因簇，另一个是具有高HLA-II基因的S100A4和A6的S100家族基因簇，一个具有独特IFITM家族基因的特定非经典单核细胞簇，以及一个独特的高转化生长因子-β（TGF-β）的Treg簇。门诊患者和血清阴性对照共享大多数具有高HLA基因表达的单核细胞和Treg簇模式。令人惊讶的是，虽然可能寿命较短的单核细胞似乎在4个月内有持续变化，但门诊患者中寿命较长的Tregs（高HLA-DRA和S100A6）频率在测试的康复期（≥4个月）内恢复。总体而言，我们的研究确定了康复后具有不同分子特征的持续且动态改变的单核细胞和Treg簇，它们与新冠严重程度相关。
