PDF(Pubmed)
Abstract：
Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8+ T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8+ T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8+ T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8+ T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection.
摘要：
针对SARS-CoV-2的特异性T细胞反应提供了大流行期间获得性免疫的概述。抗SARS-CoV-2免疫决定了急性疾病的严重程度，但也可能与症状的可能持续有关（长COVID）。我们回顾性分析了26例确诊为严重疾病的COVID-19患者的离体纵向CD8+T细胞反应，最初(1个月)和长期(10个月)，在32名接种疫苗的医护人员中，以前没有SARS-CoV-2感染。我们使用了肽-人白细胞抗原（pHLA）葡聚糖，可识别病毒和其他非结构蛋白的26种SARS-CoV-2衍生表位。大多数患者对研究的至少一种肽有反应，主要来源于非结构ORF1ab蛋白。经过10个月的随访，CD8+T细胞应答长期维持，针对某些表位的反应（A*01:01-ORF1ab1637）仍然被检测到，显示记忆样表型(CD127+PD-1+)。在这些患者中，SARS-CoV-2特异性CD8+T细胞的总数与长期COVID的保护作用显着相关。与疫苗接种相比，感染患者对HLA限制的刺突蛋白衍生肽的免疫反应效果较差。所以,A*01:01-S865和A*24:02-S1208葡聚糖仅在接种疫苗的个体中被识别。我们得出的结论是，最初的SARS-CoV-2特异性CD8T细胞反应可用作标志物，以了解SARS-CoV-2感染后严重疾病和急性后遗症的演变。
