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

Nat Commun. 2024 Aug 20;15(1):6664. doi: 10.1038/s41467-024-50339-4.

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.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • COVID-19* / blood
  • COVID-19* / immunology
  • COVID-19* / virology
  • Chemokines / blood
  • Chemokines / metabolism
  • Chlorocebus aethiops
  • Disease Models, Animal*
  • Female
  • Glycogen / metabolism
  • Humans
  • Hyperglycemia* / immunology
  • Liver* / immunology
  • Liver* / metabolism
  • Liver* / virology
  • Male
  • Pancreas / immunology
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreas / virology
  • SARS-CoV-2* / immunology
  • Virus Replication

Substances

  • Glycogen
  • Blood Glucose
  • Chemokines