Journal Article

Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates

Webb, Gabriela M., Pessoa, Cleiton, Humkey, Matthew, Thomas, Sarah, McGuire, Casey M., Zweig, Robert C., Hulahan, Jesse, Streblow, Daniel N., Lewis, Anne D., Roberts, Charles T., Colgin, Lois M. A., Blomenkamp, Hannah, Hirsch, Alec J., Bader, Lindsay, Sacha, Jonah B., Gao, Lina, Levy, Maayan, Zaro, Cicely, Kreklywich, Craig N., Sleeman, Madeleine, Kahn, Steven E., Sauter, Kristin A., Kirigiti, Melissa A., Cherry, Sara, Slifka, Mark K., Thomas, Archana, Takahashi, Diana L., Kievit, Paul

2025

Overview

Long-term adverse consequences of SARS-CoV-2 infection, termed “long COVID” or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animals / Antibodies, Viral - blood / Antibodies, Viral - immunology / B cells / Biology and Life Sciences / Body fat / Body temperature / Body weight / Care and treatment / Complications / Complications and side effects / COVID-19 / COVID-19 - complications / COVID-19 - immunology / COVID-19 - pathology / COVID-19 - virology / Cytokines / Diabetes / Disease Models, Animal / Dosage and administration / Equity / Health aspects / Immunoglobulin G / Infection / Infections / Insulin / Insulin resistance / Long COVID / Macaca mulatta / Male / Medicine and health sciences / Metabolic disorders / Monkeys & apes / Obesity / Obesity - complications / Obesity - immunology / Obesity - virology / Pandemics / Parameters / Pathology / Post-Acute COVID-19 Syndrome / Primates / Research and Analysis Methods / Research funding / Respiratory diseases / SARS-CoV-2 - immunology / Serology / Severe acute respiratory syndrome coronavirus 2 / Viral diseases