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

Abstract

Background: After acute COVID-19, five percent 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 is to measure [¹¹C]SL25.1188 total distribution volume ([¹¹C]SL25.1188 V_T), index of monoamine oxidase B (MAO-B) density and marker of astrogliosis with PET in COVID-DC and compare to healthy controls.

Methods: In 21 COVID-DC cases and 21 healthy controls, [¹¹C]SL25.1188 V_T was measured in 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 COVID-DC in prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum compared to healthy controls. Depressive symptom severity correlated negatively with [¹¹C]SL25.1188 V_T across prioritized brain regions. More recent acute COVID-19 correlated positively 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 hippocampus, dorsal putamen, and ventral striatum compared to major depressive episode controls with no history of COVID-19; and no relationship to cognitive testing in prioritized regions.

Conclusions: Results strongly support the presence of MAO-B labelled astrogliosis in COVID-DC throughout the regions assessed although the association of greater astrogliosis with less symptoms raises the possibility of a protective role. Magnitude of astrogliosis in COVID-DC is greater since emergence of omicron variant.