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

长期 COVID 非人类灵长类动物模型识别出高血糖的免疫相关因素

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作者:Clovis S Palmer #, Chrysostomos Perdios #, Mohamed Abdel-Mohsen, Joseph Mudd, Prasun K Datta, Nicholas J Maness, Gabrielle Lehmicke, Nadia Golden, Linh Hellmers, Carol Coyne, Kristyn Moore Green, Cecily Midkiff, Kelsey Williams, Rafael Tiburcio, Marissa Fahlberg, Kyndal Boykin, Carys Kenway, Kasi Ru

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.

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