Astrogliosis Marker [11C]SL25.1188 After COVID-19 With Ongoing Depressive and Cognitive Symptoms

Abstract

Background: After acute COVID-19, 5% of people experience persistent depressive symptoms and reduced cognitive function (COVID-DC). Theoretical models propose that astrogliosis is important in long COVID, but measures primarily indicative of astrogliosis have not been studied in the brain of long COVID or COVID-DC. The objective of the current study was to measure [¹¹C]SL25.1188 total distribution volume ([¹¹C]SL25.1188 V_T), an index of monoamine oxidase B density and a marker of astrogliosis, with positron emission tomography in participants with COVID-DC and compare with healthy control participants.

Methods: In 21 COVID-DC cases and 21 healthy control participants, [¹¹C]SL25.1188 V_T was measured in the prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum. Depressive symptoms were measured with the Beck Depression Inventory-II, and cognitive symptoms were measured with neuropsychological tests.

Results: [¹¹C]SL25.1188 V_T was higher in participants with COVID-DC in the prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum than in healthy control participants. Depressive symptom severity negatively correlated with [¹¹C]SL25.1188 V_T across prioritized brain regions. More recent acute COVID-19 positively correlated with [¹¹C]SL25.1188 V_T, reflecting higher values since predominance of the Omicron variant. Exploratory analyses found greater [¹¹C]SL25.1188 V_T in the hippocampus, dorsal putamen, and ventral striatum of COVID-DC participants than control participants with a major depressive episode with no history of COVID-19, and there was no relationship to cognitive testing in prioritized regions.

Conclusions: Results strongly support the presence of monoamine oxidase B-labeled astrogliosis in COVID-DC throughout the regions assessed, although the association of greater astrogliosis with fewer symptoms raises the possibility of a protective role. The magnitude of astrogliosis in COVID-DC is greater since the emergence of the Omicron variant.

Keywords: COVID-19; Depression; MAO-B; Neuroimaging; PET; [(11)C]SL25.1188.