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Immune Correlates of Hyperglycemia and Vaccination in a Non-human Primate Model of Long-COVID

Palmer, C. S.; Perdios, C.; Abdel-Mohsen, M.; Mudd, J.; Datta, P.; Maness, N.; Lehmicke, G.; Golden, N.; Hellmer, L.; Coyne, C.; Moore Green, K.; Midkiff, C.; Williams, K.; Tiburcio, R.; Fahlberg, M.; Boykin, K.; Kenway, C.; Russell-Lodrigue, K.; Bohm, R.; Blair, R. V.; Dufour, J.; Fischer, T.; Saied, A.; Rappaport, J.

2023-09-25 immunology
10.1101/2023.09.22.559019 bioRxiv
Show abstract

Hyperglycemia, 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.

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