COVID-19 的急性后期后遗症表现为外周血 CD8β7 整合素 T 细胞减少和抗 SARS-CoV-2 IgA 应答反应减弱。
Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8β7 integrin T cells and anti-SARS-CoV-2 IgA response.
机构信息
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
出版信息
Nat Commun. 2023 Mar 30;14(1):1772. doi: 10.1038/s41467-023-37368-1.
Several millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis. Both convalescent asymptomatic and PASC cases are characterised by higher CD8 T cell percentages, however, the proportion of blood CD8 T cells expressing the mucosal homing receptor β7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease. Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC. In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8β7Integrin T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.
据估计,有数百万感染者在感染后数月仍会出现急性新冠病毒后综合征(PASC)。本研究旨在评估感染后 6 个月时,PASC 患者与无症状及未感染者的免疫反应。与无症状感染者相比,PASC 患者的 CD8 T 细胞比例更高,但 PASC 患者血液中表达黏膜归巢受体 β7 的 CD8 T 细胞比例较低。PASC 患者的 CD8 T 细胞表达更高水平的 PD-1、穿孔素和颗粒酶 B,且 I 型和 III 型(黏膜型)干扰素的血浆水平升高。体液免疫反应的特征是针对 N 和 S 病毒蛋白的 IgA 水平升高,尤其是在那些急性疾病严重的个体中。我们的研究结果还表明,急性疾病期间持续升高的 IL-6、IL-8/CXCL8 和 IP-10/CXCL10 水平会增加发展为 PASC 的风险。综上所述,本研究表明,PASC 是由 SARS-CoV-2 感染后长达 6 个月的持续免疫功能障碍定义的,包括黏膜免疫参数的改变、黏膜 CD8β7Integrin T 细胞和 IgA 的重新分布,提示病毒持续存在和黏膜在 PASC 的发病机制中发挥作用。