Patients With COVID-DC May Have Higher Gliosis Levels in the Brain

Patients with persistent depressive and cognitive symptoms after COVID-19 (COVID-DC) have higher translocator protein total distribution volume (TSPO VT), a sign of elevated gliosis in the brain, according to study findings published in JAMA Psychiatry.

Following a COVID-19 infection, symptoms of depression and cognitive symptoms commonly occur. Researchers suspect that gliosis, an inflammatory change, may be involved. The researchers sought to determine whether TSPO VT is elevated in certain regions of the brain in individuals with COVID-DC.

They conducted a case-control study from April 1, 2021 to June 30, 2022, at a psychiatric facility in Canada. They recruited 40 participants aged 18 to 72, 20 of which had COVID-DC, compared with 20 healthy control individuals. Patients were classified as COVID-DC after the onset of a new major depressive episode within 3 months of COVID-19 infection confirmed with polymerase chain reaction (PCR) or rapid antigen testing. 

All patients underwent positron emission tomography (PET) scans for 120 minutes to collect TSPO VT data; arterial sampling was performed concurrently with the PET scan. Patients with COVID-DC also completed additional neuropsychological and psychological testing; testing included a motor speed test, ratings of major depressive episode severity, and self-ratings of cognitive function deficits. 

The researchers used analysis of variance (ANOVA) and mixed-effects models to compare TSPO VT between individuals with COVID-DC and healthy control individuals. They used Pearson analysis to calculate the association between TSPO VT and cognitive function; TSPO VT was measured in the dorsal putamen, prefrontal cortex, hippocampus, anterior cingulate cortex, and ventral striatum. 

The mean (SD) age of all participants was 32.9 (12.3) years. The mean (SD) age for the COVID-DC cohort was 32.7 (11.4) years and 33.3 (13.9) for the healthy control individuals; 60% of the COVID-DC cohort and 55% of the control group were women.

The researchers found that the TSPO VT levels were greater in the COVID-DC cohort compared with the control group (mean [SD] TSPO VT 9.23 [3.16] mL/cm3 vs. 7.72 [3.16] mL/cm³, respectively). The mean (SD) difference between the cohorts was 1.51 (4.47 [95% CI, 0.04-2.9; P =.04]; 1.51 divided by 9.20 [17%]). 

All brain regions tested had higher TSPO VT levels among patients with COVID-DC; the ventral striatum and dorsal putamen were found to have the greatest difference in TSPO VT levels.

The mean (SD) difference between cohorts in the ventral striatum was 1.97 (4.88 [95% CI, 0.36-3.58; P=.02]); in the dorsal putamen, the mean difference was 1.70 (4.25 [95% CI, 0.34-3.06; P= .02]). The percentage differences between cohorts in the ventral striatum were 1.97 divided by 8.87 (22%) and 1.70 divided by 8.37 (20%) in the dorsal putamen. 

TSPO VT levels were negatively correlated with motor speed measured by the finger-tapping test (r, −0.53 [95% CI, −0.79 to −0.09]). The 10 participants with the slowest motor speed in the COVID-DC cohort had mean (SD) TSPO VT levels higher by 2.3 (2.46 [95% CI, 0.92-3.68]), compared with the control group in the dorsal putamen; the percentage differences between cohorts was 2.30 divided by 8.37 (27%) when compared with control individuals.

Study limitations included that the data predominantly represents COVID-DC after mild or moderate COVID-19 infection; more severe COVID-19 infection may contribute to COVID-DC via different mechanisms.

The researchers concluded that “evidence of elevated gliosis in the brain was found in patients with COVID-DC, most prominently in the ventral striatum and dorsal putamen.”