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HIV 感染者在 SARS-COV-2 感染后出现的后遗症和适应性免疫反应。

Postacute sequelae and adaptive immune responses in people with HIV recovering from SARS-COV-2 infection.

机构信息

Division of HIV, Infectious Diseases, and Global Medicine.

Division of Experimental Medicine.

出版信息

AIDS. 2022 Oct 1;36(12):F7-F16. doi: 10.1097/QAD.0000000000003338. Epub 2022 Jul 18.

Abstract

BACKGROUND

Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).

METHODS

We measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 ( n  = 39 and n  = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing postacute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T-cell responses, as well as differences in the prevalence of PASC.

RESULTS

Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T-cell responses as compared with a well matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8 + T cells ( P  = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4 + T cells ( P  = 0.007). Higher CD4 + /CD8 + ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8 + T cells (0.34-fold effect, P  = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, P  = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.

CONCLUSION

We identified potentially important differences in SARS-CoV-2-specific CD4 + and CD8 + T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

摘要

背景

关于 HIV 感染者(PWH)感染 SARS-CoV-2 后的长期临床和免疫学后果的数据有限。

方法

我们使用结合抗体、替代病毒中和、细胞内细胞因子染色和炎症标志物检测,分别测量了从 COVID-19 中康复的有和没有 HIV 的人群(分别为 n  = 39 和 n  = 43)的 SARS-CoV-2 特异性体液和细胞反应。我们确定了经历 SARS-CoV-2 感染后急性后遗症(PASC)的个体,并评估了免疫参数。我们使用线性回归和广义线性模型来检查 HIV 状态对炎症和病毒特异性抗体和 T 细胞反应幅度的差异,以及 PASC 的患病率差异。

结果

在 PWH 中,我们发现与一组匹配良好的 HIV 阴性个体相比,SARS-CoV-2 特异性抗体和 T 细胞反应大致相似。与 SARS-CoV-2 特异性记忆 CD8 + T 细胞相比,PWH 的相对水平低 70%(P  = 0.007),与 SARS-CoV-2 特异性 CD4 + T 细胞相比,相对水平高 53%(P  = 0.007)。较高的 CD4 + /CD8 + 比值与 SARS-CoV-2 特异性 CD8 + T 细胞上较低的 PD-1 表达相关(效应为 0.34 倍,P  = 0.02)。HIV 状态与 PASC 强烈相关(优势比 4.01,P  = 0.008),某些炎症标志物(IL-6、TNF-alpha 和 IP-10)的水平与持续症状相关。

结论

我们在 PWH 和 HIV 阴性参与者中发现了 SARS-CoV-2 特异性 CD4 + 和 CD8 + T 细胞的潜在重要差异,这可能对自然感染赋予的长期免疫产生影响。HIV 状态强烈预测 PASC 的存在。迫切需要对 PWH 中的 PASC 进行更大规模和更详细的研究。

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