Distinctive changes in immune cells have been identified in people with long COVID, according to a study published on Aug. 2 by researchers at Gladstone Institutes. The findings, which appear in Cell Reports Medicine, provide new insights into the biological mechanisms underlying the condition and may help guide future research and treatment approaches.
Nadia Roan, PhD, senior investigator at Gladstone and professor at UC San Francisco, said that long COVID remains difficult to treat due to its complex and varied symptoms. "The pandemic may be behind us, but COVID-19—and its accompanying long COVID—is unfortunately here to stay. Vaccination decreases your risk of long COVID but does not prevent it, and the more times you get COVID-19, the higher your risk," Roan said.
Roan's team focused on CD8 T cells—immune cells specialized for targeting virus-infected cells—and used advanced technologies including combinatorial tetramer technology and CyTOF for their analysis. The study examined blood samples from patients who had only been infected once with SARS-CoV-2 before vaccines were available and included those with particularly severe forms of long COVID.
The researchers found that virus-specific CD8 T cells targeting SARS-CoV-2 as well as two herpesviruses (Epstein-Barr virus and cytomegalovirus) showed signs of being worn out from repeated activation in people with long COVID. "Our biggest finding was that, even though they target completely different viruses, these three virus-specific CD8 T cells shared certain features in people with long COVID that were not present in the people without long COVID," Roan said. The team also observed heightened cytolytic activity—cells' ability to destroy infected targets—in all three types of CD8 T cells among those affected by long COVID.
Roan noted that these enhanced cytolytic features were especially pronounced in women: "Long COVID is much more prevalent in women, and this reinforces how essential it is to include women in disease research." She added that while some differences were expected among SARS-CoV-2-specific CD8 T cells, the most profound changes appeared instead among cytomegalovirus-specific ones.
Looking ahead, Roan described plans for further research using mouse models of long COVID developed at Gladstone as well as expanded studies into tissue samples—including those from female reproductive tracts—to investigate sex-specific differences: "We are still in the early stages...but studies like ours will hopefully lead toward new treatments."
