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体液、细胞和细胞因子免疫应答对 COVID-19 恢复期和确诊患者不同疾病严重程度的 SARS-CoV-2 变异株的反应。

Humoral, Cellular and Cytokine Immune Responses Against SARS-CoV-2 Variants in COVID-19 Convalescent and Confirmed Patients With Different Disease Severities.

机构信息

Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.

出版信息

Front Cell Infect Microbiol. 2022 May 17;12:862656. doi: 10.3389/fcimb.2022.862656. eCollection 2022.

Abstract

OBJECTIVES

To assess humoral and cellular immune responses against SARS-CoV-2 variants in COVID-19 convalescent and confirmed patients, to explore the correlation between disease severity, humoral immunity, and cytokines/chemokines in confirmed patients, and to evaluate the ADE risk of SARS-CoV-2.

METHODS

Anti-RBD IgG were quantified using an ELISA. Neutralization potency was measured using pseudovirus and real virus. Cellular immunity was measured using ELISpot. Cytokine/chemokine levels were detected using multiplex immunoassays. ADE assays were performed using Raji cells.

RESULTS

One-month alpha convalescents exhibited spike-specific antibodies and T cells for alpha and delta variants. Notably, the RBD-specific IgG towards the delta variant decreased by 2.5-fold compared to the alpha variant. Besides, serum from individuals recently experienced COVID-19 showed suboptimal neutralizing activity against the delta and omicron variants. Humoral immune response, IL-6, IP-10 and MCP-1 levels were greater in patients with severe disease. Moreover, neither SARS-CoV-1 nor SARS-CoV-2 convalescent sera significantly enhanced SARS-CoV-2 pseudovirus infection.

CONCLUSIONS

Significant resistance of the delta and omicron variants to the humoral immune response generated by individuals who recently experienced COVID-19. Furthermore, there was a significant correlation among disease severity, humoral immune response, and specific cytokines/chemokine levels. No evident ADE was observed for SARS-CoV-2.

摘要

目的

评估 COVID-19 恢复期和确诊患者对 SARS-CoV-2 变体的体液和细胞免疫反应,探讨确诊患者疾病严重程度、体液免疫和细胞因子/趋化因子之间的相关性,并评估 SARS-CoV-2 的抗体依赖性增强(ADE)风险。

方法

使用 ELISA 定量测定抗 RBD IgG。使用假病毒和真病毒测量中和效力。使用 ELISpot 测量细胞免疫。使用多重免疫分析检测细胞因子/趋化因子水平。使用 Raji 细胞进行 ADE 测定。

结果

一个月的 alpha 恢复期患者表现出针对 alpha 和 delta 变体的 spike 特异性抗体和 T 细胞。值得注意的是,与 alpha 变体相比,针对 delta 变体的 RBD 特异性 IgG 下降了 2.5 倍。此外,最近经历过 COVID-19 的个体的血清对 delta 和 omicron 变体的中和活性较低。疾病严重程度较高的患者具有更高的体液免疫反应、IL-6、IP-10 和 MCP-1 水平。此外,SARS-CoV-1 或 SARS-CoV-2 恢复期血清均未显著增强 SARS-CoV-2 假病毒感染。

结论

最近经历过 COVID-19 的个体产生的针对 delta 和 omicron 变体的体液免疫反应具有显著的抗性。此外,疾病严重程度、体液免疫反应和特定细胞因子/趋化因子水平之间存在显著相关性。未观察到 SARS-CoV-2 的明显 ADE。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf0/9152113/de8d7090f032/fcimb-12-862656-g001.jpg

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