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

Abstract

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 VT), index of monoamine oxidase B (MAO-B) density and marker of astrogliosis with PET in COVID-DC and compare to healthy controls. In 21 COVID-DC cases and 21 healthy controls, [11C]SL25.1188 VT 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. [11C]SL25.1188 VT 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 VT across prioritized brain regions. More recent acute COVID-19 correlated positively with [11C]SL25.1188 VT, reflecting higher values since predominance of the omicron variant. Exploratory analyses found greater [11C]SL25.1188 VT 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. 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.