Journal Article

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

Dufour, Jason P., Tiburcio, Rafael, Moore Green, Kristyn, Abdel-Mohsen, Mohamed, Saied, Ahmad A., Maness, Nicholas J., Palmer, Clovis S., Mudd, Joseph, Blair, Robert, Coyne, Carol, Russell-Lodrigue, Kasi, Boykin, Kyndal, Perdios, Chrysostomos, Birnbaum, Angela, Midkiff, Cecily, Rappaport, Jay, Datta, Prasun K., Williams, Kelsey, Hellmers, Linh, Lehmicke, Gabrielle, Kenway, Carys, Bohm, Rudolf, Golden, Nadia, Fischer, Tracy, Fahlberg, Marissa

2024

Overview

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. After infection with SARS-CoV-2 a diverse set of symptoms remain or develop longer term in a condition termed long-CoVID, yet an accurate and tractable model has remained elusive. Here the authors present a non-human primate model of long-CoVID and show persistent hyperglycemia following acute infection.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/21 / 13/31 / 13/51 / 14/63 / 631/250/255/2514 / 631/326/596/4130 / 692/308/1426 / 692/699/317 / Animal models / Animals / Blood Glucose - metabolism / Chemokines / Chemokines - blood / Chemokines - metabolism / Chlorocebus aethiops / Complications / COVID-19 / COVID-19 - blood / COVID-19 - immunology / COVID-19 - virology / Disease Models, Animal / Female / Glucose metabolism / Glycogen / Glycogen - metabolism / Glycogens / Humanities and Social Sciences / Humans / Hyperglycemia / Hyperglycemia - immunology / Infections / Liver / Liver - immunology / Liver - metabolism / Liver - virology / Long COVID / Male / Metabolism / Monkeys / mRNA / multidisciplinary / Pancreas - immunology / Pancreas - metabolism / Pancreas - pathology / Pancreas - virology / Persistent infection / Primates / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Viral diseases / Virus Replication