Neuroimaging Gliosis in Peripheral Inflammatory Diseases of COVID-19 and Inflammatory Bowel Disease
Bibliographic record
Abstract
Neuropsychiatric symptoms, including mood disturbances and cognitive impairments, are common in peripheral inflammatory diseases. Long COVID and inflammatory bowel disease (IBD) are two impactful conditions characterized by chronic systemic inflammation and significant neuropsychiatric comorbidities. Mechanisms linking systemic inflammation to brain dysfunction propose neuroinflammation as an important mediator, however, direct evidence of neuroinflammation in these populations is lacking. This thesis applies state of the art imaging methods to investigate gliosis, a hallmark of neuroinflammation, in long COVID and IBD. Positron emission tomography (PET) imaging was used, applying [18F]FEPPA to assess translocator protein (TSPO), a marker primarily of microglial activation, and [11C]SL25.1188 to assess monoamine oxidase B (MAO-B), a marker of astrogliosis. Three studies were conducted to compare markers of gliosis in these illnesses to healthy controls. Study 1 identified greater [18F]FEPPA total distribution volume ([18F]FEPPA VT) in the brain in long COVID, with the largest increases in the dorsal putamen (DP) and ventral striatum (VS) suggesting microglial and/or astroglial activation in long COVID. Higher [18F]FEPPA VT in the DP correlated with reduced motor speed, raising the possibility of a mechanistic relationship. Study 2 assessed astrogliosis marker MAO-B binding in long COVID, revealing greater [11C]SL25.1188 VT total distribution volume ([11C]SL25.1188 VT) across gray matter regions. Higher [11C]SL25.1188 VT inversely correlated with depressive symptom severity, suggesting a potential protective role of astrogliosis in long COVID. Study 3 investigated gliosis in IBD, also demonstrating significant elevations in [11C]SL25.1188 VT across gray matter regions. In the VS, it was significantly associated with work/school impairment. [18F]FEPPA VT elevations in IBD were highest in individuals with lower scores in tasks for executive function and verbal learning/memory. These findings provide strong support for presence of gliosis in the brain of IBD, and the correlations with symptoms suggest possible roles for gliosis in associated functional and cognitive impairments. The studies presented provide the first strong evidence of neuroinflammation in long COVID and IBD in humans, with implications in neuropsychiatric comorbidities. This research highlights gliosis as a potential therapeutic target, suggesting gliosis-modulating interventions, such as P2X7 inhibitors, TSPO-binding agents, and astrocyte-directed therapies, should be tested in clinical trials to assess whether they alleviate neuropsychiatric symptoms in long COVID and IBD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".