Astrogliosis marker [11C]SL2511.88 After COVID-19 With Ongoing Depressive and Cognitive Symptoms

Introduction: After acute COVID-19, persistent depressive and cognitive symptoms occur in ~5% of cases (COVID-DC). Theoretical models of COVID-DC suggest astrogliosis is important but measures primarily indicative of astrogliosis have not been studied in COVID-DC.

Methods: In this case-control study, positron emission tomography (PET) is used to determine if [¹¹C]SL2511.88 total distribution volume (), an index of monoamine oxidase B (MAO-B) density and marker of astrogliosis (outside midbrain) is elevated in COVID-DC. In 21 COVID-DC cases and 21 healthy controls [¹¹C]SL2511.88 V_T was measured in prefrontal cortex (PFC), anterior cingulate cortex (ACC), hippocampus, dorsal putamen (DP) and ventral striatum (VS). Depressive and cognitive symptoms were measured with psychological and neuropsychological tests. Data collection and analysis for participants with current major depressive episode without history of COVID-19 is ongoing; n=21 is anticipated at the time of presentation.

Results: [¹¹C]SL2511.88 V_T was greater in COVID-DC compared to healthy across prioritized regions by ~20% (p=0.001), as well as most grey matter regions. MDE severity, measured by the Beck Depression Inventory-2 negatively correlated with [¹¹C]SL2511.88 V_T in PFC, ACC, DP and VS, r=-0.55 (p=0.02) to -0.48 (p=0.04)). The 10 least severe COVID-DC cases had higher [¹¹C]SL2511.88 V_T than the 9 most severe across regions of interest by 18% (p=0.01). More recent acute COVID-19 correlated with greater [¹¹C]SL2511.88 V_T, r=0.61 (p=0.003) to 0.74 (p=0.0001), reflecting higher values since predominance of the omicron variant.

Conclusions: MAO-B labelled astrogliosis occurs throughout grey matter regions in COVID-DC. However, greater astrogliosis associated with lesser symptom severity, raising the possibility of a protective role in COVID-DC, such as combatting infection. Degree of astrogliosis in COVID-DC has not decreased since emergence of omicron variant.