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

非人灵长类动物新冠长期模型揭示高血糖的免疫关联

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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 Russell-Lodrigue ,Angela Birnbaum ,Rudolf Bohm ,Robert Blair ,Jason P Dufour ,Tracy Fischer ,Ahmad A Saied ,Jay Rappaport

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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