Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.
Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.
Clin Microbiol Infect. 2021 Feb;27(2):286.e7-286.e13. doi: 10.1016/j.cmi.2020.09.051. Epub 2020 Oct 10.
To examine whether specific T-cell-responses to SARS-CoV-2 peptides can be detected in COVID-19 using a whole-blood experimental setting, which may be further explored as a potential diagnostic tool.
We evaluated interferon (IFN)-γ levels after stimulating whole-blood with spike and remainder-antigens peptides megapools (MP) derived from SARS-CoV-2 sequences; interleukin (IL)-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, eotaxin, basic fibroblast growth factor (FGF), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-γ, Interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, Platelet-derived growth factor (PDGF), RANTES (regulated on activation, normal T cell expressed and secreted), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF) were also evaluated.
IFN-γ-response to spike and remainder-antigens MPs was significantly increased in 35 COVID-19 patients compared with 29 'no COVID-19' individuals (medians spike-MP: 0.26 vs 0, p = 0.0002; medians remainder-antigens-MP: 0.07 vs 0.02; p = 0.02). This response was detected independently of patients' clinical parameters. IFN-γ-response to SARS-CoV-2-unrelated antigens cytomegalovirus (CMV) and Staphylococcal Enterotoxin B (SEB) was similar in COVID-19 compared with 'no COVID-19' individuals (median CMV: 3.46 vs 5.28, p = 0.16; median SEB: 12.68 vs 15.05; p = 0.1). In response to spike-MPs in COVID-19- compared with 'no COVID-19' -individuals, we found significant higher median of IL-2 (50.08 vs 0, p = 0.0018), IFN-γ (90.16 vs 0, p = 0.01), IL-4 (0.52 vs 0, p = 0.03), IL-13 (0.84 vs 0, p = 0.007) and MCP-1 (4602 vs 359.2, p = 0.05).
Immune response to SARS-CoV-2 peptides in a whole-blood assay is associated with COVID-19 and it is characterized by both Th1 and Th2 profile. This experimental approach may be useful for developing new T-cell based diagnostic tests for disease and vaccine settings.
使用全血实验设置来研究 COVID-19 中是否可以检测到针对 SARS-CoV-2 肽的特异性 T 细胞反应，这可能进一步探索作为潜在的诊断工具。
我们评估了刺激全血后的干扰素（IFN）-γ水平，刺激物为来自 SARS-CoV-2 序列的刺突和剩余抗原肽巨池（MP）；白细胞介素（IL）-1β、IL-1RA、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-9、IL-10、IL-12p70、IL-13、IL-15、IL-17A、嗜酸性粒细胞趋化因子（eotaxin）、碱性成纤维细胞生长因子（FGF）、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、IFN-γ、干扰素诱导蛋白 10（IP-10）、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、血小板衍生生长因子（PDGF）、调节活化正常 T 细胞表达和分泌（RANTES）、肿瘤坏死因子-α（TNF-α）、血管内皮生长因子（VEGF）。
与 29 名“无 COVID-19”个体相比，35 名 COVID-19 患者的刺突和剩余抗原 MPs 的 IFN-γ 反应明显增加（刺突-MP 的中位数：0.26 与 0，p=0.0002；剩余抗原-MP 的中位数：0.07 与 0.02，p=0.02）。这种反应是在独立于患者临床参数的情况下检测到的。与“无 COVID-19”个体相比，COVID-19 患者对 SARS-CoV-2 无关抗原巨细胞病毒（CMV）和葡萄球菌肠毒素 B（SEB）的 IFN-γ 反应相似（CMV 的中位数：3.46 与 5.28，p=0.16；SEB 的中位数：12.68 与 15.05，p=0.1）。与“无 COVID-19”个体相比，COVID-19 患者对刺突-MP 的反应中，我们发现中位数 IL-2（50.08 与 0，p=0.0018）、IFN-γ（90.16 与 0，p=0.01）、IL-4（0.52 与 0，p=0.03）、IL-13（0.84 与 0，p=0.007）和 MCP-1（4602 与 359.2，p=0.05）的显著升高。
全血检测中针对 SARS-CoV-2 肽的免疫反应与 COVID-19 相关，其特征是 Th1 和 Th2 谱均存在。这种实验方法可能有助于开发用于疾病和疫苗设置的新型基于 T 细胞的诊断测试。
