Author:
Palmer Clovis S,Perdios Chrysostomos,Abdel-Mohsen Mohamed,Mudd Joseph,Datta Prasun,Maness Nicholas J.,Lehmicke Gabrielle,Golden Nadia,Hellmer Lihn,Coyne Carol,Green Kristyn Moore,Midkiff Cecily,Williams Kelsey,Tiburcio Rafael,Fahlberg Marissa,Boykin Kyndal,Kenway Carys,Russell-Lodrigue Kasi,Birnbaum Angela,Bohm Rudolf,Blair Robert,Dufour Jason,Fischer Tracy,Saied Ahmed A,Rappaport Jay
Abstract
AbstractHyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are major manifestations of the post-acute sequelae of SARS-CoV-2 (PASC). Our understanding of lasting glucometabolic disruptions after acute COVID-19 remains unclear due to the lack of animal models for metabolic PASC. Here, we report a non-human primate model of metabolic PASC using SARS-CoV-2 infected African green monkeys (AGMs). Using this model, we have identified a dysregulated chemokine signature and hypersensitive T cell population during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. This persistent hyperglycemia correlates with elevated hepatic glycogen, but there was no evidence of 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 AGM metabolic PASC model exhibits important similarities to human metabolic PASC and can be utilized to assess therapeutic candidates to combat this syndrome.
Publisher
Cold Spring Harbor Laboratory