PDF(Pubmed)
Abstract：
BACKGROUND: Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19.
METHODS: For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology.
RESULTS: CD4+ T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033).
CONCLUSIONS: Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles.
METHODS: For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology.
RESULTS: CD4+ T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033).
CONCLUSIONS: Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles.
摘要：
背景：严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）感染的预后预测因素仍有待完全确定。我们评估了可能预测COVID-19临床结果和/或与之相关的选定病毒特征和免疫反应。
方法：对于出现不同临床结果的个体，在症状发作后36小时内测量T细胞介导的反应的幅度和广度。用基于SARS-CoV-2的肽对外周血单核细胞(PBMC)进行体外刺激。此外,SARS-CoV-2序列由宏基因组产生，使用Luminex技术进行HLA分型。
结果：重症COVID-19患者CD4+T细胞活化与SARS-CoV-2基础病毒载量呈负相关(p=0.043)。整体的细胞免疫反应，由IFN-γ信号推断，与进展为严重疾病的患者相比，进展为轻度疾病的患者在基线时较高（p=0·0044）。患有轻度疾病的受试者对MHCI类和II类限制性肽产生了更高的T细胞应答(p=0·033)。
结论：在症状发作后的头几天增加特异性细胞免疫反应，根据ELISPOT测定中IFN-γ的大小推断，可以有效地支持积极的结果。相比之下,进展为严重的COVID-19伴随着更强的细胞免疫反应，更高的CD4+T细胞活化，和更多数量的计算机预测的高亲和力I类HLA等位基因。
方法：对于出现不同临床结果的个体，在症状发作后36小时内测量T细胞介导的反应的幅度和广度。用基于SARS-CoV-2的肽对外周血单核细胞(PBMC)进行体外刺激。此外,SARS-CoV-2序列由宏基因组产生，使用Luminex技术进行HLA分型。
结果：重症COVID-19患者CD4+T细胞活化与SARS-CoV-2基础病毒载量呈负相关(p=0.043)。整体的细胞免疫反应，由IFN-γ信号推断，与进展为严重疾病的患者相比，进展为轻度疾病的患者在基线时较高（p=0·0044）。患有轻度疾病的受试者对MHCI类和II类限制性肽产生了更高的T细胞应答(p=0·033)。
结论：在症状发作后的头几天增加特异性细胞免疫反应，根据ELISPOT测定中IFN-γ的大小推断，可以有效地支持积极的结果。相比之下,进展为严重的COVID-19伴随着更强的细胞免疫反应，更高的CD4+T细胞活化，和更多数量的计算机预测的高亲和力I类HLA等位基因。
