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

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.

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Publication Details

Journal
PLoS Pathogens
Published
2025-07-24
DOI
https://doi.org/10.1371/journal.ppat.1012988
Primary Topic
Long-Term Effects of COVID-19
Type
article
Field-Weighted Citation Impact
0.00

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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

Anne D. Lewis, Paul Kievit, Craig N. Kreklywich, Charles T. Roberts et al.
PLoS Pathogens
Long-Term Effects of COVID-19
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

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

Abstract

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.

PLoS PathogensVol. 21(7)
Oregon National Primate Research Center (US), Oregon Health & Science University (US), University of Washington (US), VA Puget Sound Health Care System (US), Oregon Physics (United States) (US), University of Pennsylvania (US)
NIH Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases
Good health and well-being
Openalex Percentile: Top 72%
Long-Term Effects of COVID-19
DOIOpen Access PDFOpenAlex
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