# 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

## TL;DR

Obesity affects long-term responses to SARS-CoV-2 infection in nonhuman primates, potentially increasing the prevalence of long COVID.

## Contribution

This study reveals how pre-existing obesity modifies both acute and post-acute responses to SARS-CoV-2 infection in a nonhuman primate model.

## Key findings

- Obese animals showed distinct lung pathology, body weight changes, and adipocytokine profiles compared to lean animals.
- SARS-CoV-2 infection altered characteristics in lean animals to resemble those in obese animals.
- Persistent changes in multiple parameters suggest PASC may be more prevalent than previously estimated.

## 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.

The COVID-19 pandemic resulted in significant illness and death due to complications of acute infection but has also resulted in a chronic condition called long COVID. Individuals who are obese or who have other aspects of metabolic disease such as hypertension or diabetes are susceptible to more severe acute COVID-19, while the risk for developing new metabolic disease is increased after apparent recovery. Since the COVID-19 pandemic coincided with the ongoing global epidemic of obesity, an important question is how pre-existing obesity affects the long-term responses to SARS-CoV-2 infection. We compared the short and long-term effects of SARS-CoV-2 infection in lean and obese rhesus macaques over the 6 months following initial infection. While the levels of virus in the respiratory system, SARS-CoV-2-specific antibodies, and inflammatory factors in the blood were not different between lean and obese animals, other responses such as lung damage, body weight, body temperature, and nighttime activity levels were different in lean versus obese animals. Furthermore, some characteristics of lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Since many of these changes were present in most animals, long COVID may be more prevalent than estimated from self-reported symptoms in human studies.