PET imaging has revealed neuroinflammation in a subset of individuals with persistent severe fatigue and difficulty concentrating more than two years after COVID-19 infection, according to a study published September 11 in the Journal of Nuclear Medicine.
The finding is from an analysis of PET scans that used F-18 DPA-714 radiotracer — a tracer that binds to a neuroinflammation biomarker called translocator protein (TSPO) — in individuals with long-COVID symptoms compared with previously infected patients without symptoms, noted lead author Denise Visser, MD, of Amsterdam UMC in the Netherlands, and colleagues.
“Increased inflammatory activity was found on TSPO-PET in some individuals with post-COVID syndrome, indicating the presence of an inflammatory subtype and suggesting that F-18 DPA-714 PET can serve as a biomarker,” the group wrote.
Long COVID is defined as the persistence or recurrence of symptoms three months after an initial infection with the SARS-CoV-2 virus. The underlying mechanisms and long-term effects of the syndrome remain poorly understood, the authors explained.
While postmortem studies of patients with COVID-19 have shown extensive brain inflammation, including brain immune cell (microglia) activation and astrogliosis, direct in vivo evidence of microglia activation is limited, they added.
Given that TSPO expression in the brain increases in activated microglia, the researchers hypothesized that PET imaging with a TSPO radiotracer (F-18 DPA-714) would provide additional evidence on these mechanisms.
The study included 47 patients, 33 of whom had severe fatigue and difficulty concentrating (median age, 50), and 14 previously infected patients who did not have these complaints (median age, 47). Two years after initial infection, participants underwent 60-minute whole-body PET scans either on an Ingenuity TF PET/CT scanner (Philips; n = 10) or on a Biograph Vision Quadra (Siemens Healthineers; n = 37). The researchers analyzed differences in F-18 DPA-714 binding levels across four cerebral and nine extracerebral regions between the groups.
After adjusting for age, body mass index, and PET scanner type, the researchers found significantly higher binding in global gray matter in individuals with versus without persistent complaints (nondisplaceable binding potential, 0.8 ± 0.34 vs. 0.65 ± 0.17, p = 0.036). Additionally, while no significant differences in binding levels of the other regions were observed between groups, visual inspection showed similar high binding levels in the cerebellum in some with persistent complaints compared to those without complaints.
Examples of quantitative cerebral F-18 DPA-714 images of brain in post-COVID individuals. *Parametric Logan VT images corrected for K1/k2 (global cerebral region; gray and white matter) and subtracted by 1, creating indirect BPND images. VT = total distribution volume.Journal of Nuclear Medicine“We found widespread elevated neuroinflammatory activity, as measured with TSPO-PET, in some post-COVID individuals with persistent severe fatigue and/or difficulty concentrating compared with individuals without these complaints,” the group wrote.
In addition to hinting at the pathophysiology of long COVID, the diagnosis of chronic neuroinflammatory activity in these patients is important, the researchers noted.
“As we know from other diseases, such as multiple sclerosis, Alzheimer disease, and Parkinson disease, chronic neuroinflammation is associated with neurodegeneration and may be equally relevant for post-COVID syndrome,” the group wrote.
The full study is available here.