A study comparing the effects of SARS-CoV-2 infection in lean and obese primates found different long-term consequences of the virus depending on prior obesity and metabolic disease.

The results, which also highlight how widespread long COVID symptoms are in animals, are published in PLOS Pathogens by Charles Roberts of Oregon Health & Science University, U.S., and colleagues.

Long-term adverse consequences of SARS-CoV-2 infection, termed “long COVID” or post-acute sequelae of COVID (PASC), are a major component of the overall COVID-19 disease burden. Prior obesity and metabolic disease are known to increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease.

In the new study, researchers studied the effects of infection with the SARS-CoV-2 delta variant in lean as well as obese and insulin-resistant adult male rhesus macaques over a 6-month time course. The majority of animals had consistently altered parameters months after the resolution of initial infection. Levels of virus in the respiratory system, viral antibodies, and inflammatory factors in the blood were generally similar between lean and obese animals. Other responses varied by metabolic status.

While obesity increased risks like persistent lung damage and longer-term weight loss, lean animals were more likely to develop signs of metabolic disruption. Notably, lean animals experienced a significant decline in the ratio of the blood concentration of the hormone adiponectin to that of the hormone leptin, thereby lowering their level of this metabolic health marker to the level seen in obese peers.

Because many long-term effects were physiological rather than symptomatic, the study suggests long COVID may be more common than human self-report data indicates.

“Some parameters changed more robustly in obese animals, while others changed more robustly in lean animals. Thus, persistent effects of SARS-CoV-2 infection are both obesity-dependent and independent,” the authors say.

Dr. Roberts says, “I think one of the most striking results of our study was the extent of long-term adverse effects seen after what outwardly appeared to be a very mild initial disease course. This suggests that long COVID can indeed result from a mild infection.

“Since we saw increased levels of inflammatory factors and changes in biomarkers of cardiometabolic disease risk six months after infection, some symptoms of long COVID may only become apparent long after the initial infection.”

Co-author Dr. Kristin Sauter notes, “Our development of a macaque model of long COVID will allow us to directly compare the intrinsic differences between the effects of the delta variant described in this study with the effects of later variants such as omicron, which is the subject of our current NIH-supported work.

“This is possible because the macaques used in our studies have never been exposed to the SARS-CoV-2 virus previously, so any different responses can be attributed to differences in the variants themselves, rather than being due to varying levels of existing immunity, which complicate human studies.”