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SARS-CoV-2 特异性适应性免疫应答与康复期 COVID-19 重症患者。

Adaptive immune responses to SARS-CoV-2 in recovered severe COVID-19 patients.

机构信息

Microbiology Service, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain.

Hematology Service, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain.

出版信息

J Clin Virol. 2021 Sep;142:104943. doi: 10.1016/j.jcv.2021.104943. Epub 2021 Aug 8.

Abstract

BACKGROUND

There is an imperative need to determine the durability of adaptive immunity to SARS-CoV-2. We enumerated SARS-CoV-2-reactive CD4 and CD8 T cells targeting S1 and M proteins and measured RBD-specific serum IgG over a period of 2-6 months after symptoms onset in a cohort of subjects who had recovered from severe clinical forms of COVID-19.

PATIENTS AND METHODS

We recruited 58 patients (38 males and 20 females; median age, 62.5 years), who had been hospitalized with bilateral pneumonia, 60% with one or more comorbidities. IgG antibodies binding to SARS-CoV-2 RBD were measured by ELISA. SARS-CoV-2-reactive CD69-expressing-IFNγ-producing-CD4 and CD8 T cells were enumerated in heparinized whole blood by flow cytometry for ICS.

RESULTS

Detectable SARS-CoV-2-S1/M-reactive CD69-IFN-γ CD4 and CD8 T cells were displayed in 17 (29.3%) and 6 (10.3%) subjects respectively, at a median of 84 days after onset of symptoms (range, 58-191 days). Concurrent comorbidities increased the risk (OR, 3.15; 95% CI, 1.03-9.61; P = 0.04) of undetectable T-cell responses in models adjusted for age, sex and hospitalization ward. Twenty-one out of the 35 patients (60%) had detectable RBD-specific serum IgGs at a median of 118 days (range, 60-145 days) after symptoms onset. SARS-CoV-2 RBD-specific IgG serum levels were found to drop significantly over time.

CONCLUSION

A relatively limited number of subjects who developed severe forms of COVID-19 had detectable SARS-CoV-2-S1/M IFNγ CD4 and CD8 T cells at midterm after clinical diagnosis. Our data also indicated that serum levels of RBD-specific IgGs decline over time, becoming undetectable in some patients.

摘要

背景

确定对 SARS-CoV-2 的适应性免疫的持久性是当务之急。我们对从严重临床型 COVID-19 中康复的患者队列,在症状发作后 2-6 个月期间,对 S1 和 M 蛋白靶向的 SARS-CoV-2 反应性 CD4 和 CD8 T 细胞进行了计数,并测量了 RBD 特异性血清 IgG。

患者和方法

我们招募了 58 名患者(38 名男性和 20 名女性;中位年龄 62.5 岁),这些患者因双侧肺炎住院,60%的患者合并一种或多种合并症。通过 ELISA 测量与 SARS-CoV-2 RBD 结合的 IgG 抗体。通过 ICS 用流式细胞术在肝素化全血中对 SARS-CoV-2 反应性 CD69 表达 IFNγ产生的 CD4 和 CD8 T 细胞进行计数。

结果

在症状发作后中位时间 84 天(范围 58-191 天),分别有 17 名(29.3%)和 6 名(10.3%)患者检测到可检测的 SARS-CoV-2-S1/M-反应性 CD69-IFN-γ CD4 和 CD8 T 细胞。同时存在合并症会增加模型中未检测到 T 细胞反应的风险(OR,3.15;95%CI,1.03-9.61;P=0.04),模型中调整了年龄、性别和住院病房因素。在症状发作后中位时间 118 天(范围 60-145 天),35 名患者中的 21 名(60%)检测到可检测的 RBD 特异性血清 IgG。SARS-CoV-2 RBD 特异性 IgG 血清水平随时间显著下降。

结论

在临床诊断后中期,只有少数发生严重 COVID-19 的患者可检测到 SARS-CoV-2-S1/M IFNγ CD4 和 CD8 T 细胞。我们的数据还表明,RBD 特异性 IgGs 的血清水平随时间下降,在一些患者中无法检测到。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/433c/8349475/57c0b0e5c7b6/gr1_lrg.jpg

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