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严重 COVID-19 和长新冠与 STING、cGAS 和 IFN-α 的高表达有关。

Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α.

机构信息

Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.

Graduate Program in Biology of Infectious and Parasitic Agents, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.

出版信息

Sci Rep. 2024 Feb 29;14(1):4974. doi: 10.1038/s41598-024-55696-0.

DOI:10.1038/s41598-024-55696-0
PMID:38424312
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10904751/
Abstract

The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.

摘要

cGAS-STING 通路似乎与 2019 年冠状病毒病(COVID-19)期间失调的炎症有关;然而,与长新冠相关的炎症因子仍在研究中。在本研究中,我们评估了 cGAS 和 STING 基因表达水平以及血浆 IFN-α、TNF-α 和 IL-6 水平与急性感染和长新冠期间 COVID-19 严重程度的相关性,分析了来自 148 个人的血液样本,其中 87 人患有急性 COVID-19,61 人处于 COVID-19 后时期。通过实时 PCR 进行基因表达定量,通过 ELISA 和流式细胞术定量细胞因子水平。在急性 COVID-19 中,重症患者的 cGAS、STING、IFN-α、TNF-α 和 IL-6 水平高于非重症患者(p<0.05)。长新冠与 cGAS、STING 和 IFN-α 水平升高有关(p<0.05)。cGAS-STING 通路的激活可能导致严重 COVID-19 中强烈的全身炎症状态,并且在感染消退后,在某些组织中诱导自身炎症性疾病,导致长新冠。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/4e5b050a2683/41598_2024_55696_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/f4a0223d72ae/41598_2024_55696_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/4f1ad227ee25/41598_2024_55696_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/9df74ef40d9f/41598_2024_55696_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/b8d7827a9515/41598_2024_55696_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/2be82a9761fc/41598_2024_55696_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/4e5b050a2683/41598_2024_55696_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/f4a0223d72ae/41598_2024_55696_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/4f1ad227ee25/41598_2024_55696_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/9df74ef40d9f/41598_2024_55696_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/b8d7827a9515/41598_2024_55696_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/2be82a9761fc/41598_2024_55696_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b9c/10904751/4e5b050a2683/41598_2024_55696_Fig6_HTML.jpg

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