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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

  • 0Division of Metabolic Health and Disease, Oregon National Primate Research Center (ONPRC), Beaverton, OR, USA.
Biorxiv : the Preprint Server for Biology +

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March 3, 2025

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March 3, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Obesity significantly alters long-term responses to SARS-CoV-2 infection, potentially increasing the risk of post-acute sequelae of COVID (PASC) even in lean individuals. This study used a nonhuman primate model to investigate these effects.

Area Of Science

  • Virology
  • Immunology
  • Metabolic Disease

Background

  • Long-term adverse consequences of SARS-CoV-2 infection, known as post-acute sequelae of COVID (PASC), contribute significantly to the overall disease burden.
  • Pre-existing obesity and metabolic diseases exacerbate acute SARS-CoV-2 infection severity and can lead to new-onset metabolic dysfunction post-infection.

Purpose Of The Study

  • To investigate how pre-existing obesity modifies long-term responses to SARS-CoV-2 infection.
  • To compare the effects of SARS-CoV-2 delta variant infection in lean versus obese/insulin-resistant rhesus macaques over a six-month period.

Main Methods

  • Utilized a nonhuman primate model (rhesus macaques) with distinct lean and obese/insulin-resistant phenotypes.
  • Infected animals with the SARS-CoV-2 delta variant and monitored viral dynamics, immune responses, metabolic parameters, and clinical signs over six months.

Main Results

  • While viral dynamics and initial immune responses were similar, obese animals exhibited distinct changes in neutralizing antibody dynamics, lung pathology, body weight, insulin sensitivity, and adipocytokine profiles compared to lean animals.
  • SARS-CoV-2 infection altered several parameters in lean animals, making them resemble those observed in obese animals.
  • Persistent changes in multiple parameters were observed in most infected animals, suggesting a higher prevalence of PASC than previously estimated.

Conclusions

  • Pre-existing obesity significantly influences the host response to SARS-CoV-2 infection, leading to distinct long-term sequelae.
  • SARS-CoV-2 infection can induce metabolic and physiological changes that mimic aspects of obesity, even in previously lean individuals.
  • The findings suggest that PASC may be more prevalent and have a broader impact than indicated by self-reported symptoms alone.