Tulane National Primate Research Center, Covington, LA, USA.
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
Nat Commun. 2024 Aug 20;15(1):6664. doi: 10.1038/s41467-024-50339-4.
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.
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。