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长新冠非人类灵长类动物模型鉴定出与高血糖相关的免疫标志物。

Non-human primate model of long-COVID identifies immune associates of hyperglycemia.

机构信息

Tulane National Primate Research Center, Covington, LA, USA.

Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.

出版信息

Nat Commun. 2024 Aug 20;15(1):6664. doi: 10.1038/s41467-024-50339-4.

Abstract

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects.

摘要

高血糖症,以及先前存在的葡萄糖代谢缺陷的恶化,是 SARS-CoV-2 急性后遗症的表现。由于缺乏动物模型,我们对急性 COVID-19 后代谢下降的认识仍不清楚。在这里,我们使用感染 SARS-CoV-2 的非洲绿猴报告了 SARS-CoV-2 代谢急性后遗症的非人类灵长类动物模型。使用该模型,我们在急性 COVID-19 期间发现了一个失调的血液趋化因子特征,该特征与感染后四个月升高和持续的高血糖症相关。高血糖症还与肝糖原水平相关,但没有证据表明肝脏和胰腺中有大量长期的 SARS-CoV-2 复制。最后,我们报告了 SARS-CoV-2 mRNA 疫苗在感染后第 4 天给药的良好降血糖作用。总之,这些数据表明,非洲绿猴模型与人类具有重要的相似性,可以用于评估治疗候选药物以对抗与 COVID 相关的代谢缺陷。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1576/11335872/44af1ddefb26/41467_2024_50339_Fig1_HTML.jpg

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