Loss of vesicular monoamine transporter 2 in striatum of long COVID and relationship to neuropsychiatric symptoms.

Abstract

Dopaminergic neurons are vulnerable to injury from gliosis and have high density of ACE2 receptors, but the integrity of dopaminergic neurons has not been investigated in long COVID. This study examined whether vesicular monoamine transporter 2 (VMAT2) binding, index of dopamine-releasing neuron density, is reduced in the striatum in long COVID and associated with neuropsychiatric symptoms. This case-control study (Aug 2022-Apr 2025, Toronto, Canada) included 24 adults with long COVID and 24 age-matched healthy controls, and the healthy control sample was extended to 43 for exploratory analyses. Primary outcome was comparison of (+)[¹¹C]DTBZ binding potential (BP_ND), PET measure of VMAT2 binding, between long COVID and control groups across ventral striatum, dorsal putamen, and dorsal caudate. Secondary outcomes were associations of regional (+)[¹¹C]DTBZ BP_ND with neuropsychiatric measures (apathy, anhedonia, motor retardation) in long COVID. (+)[¹¹C]DTBZ BP_ND was significantly lower in 24 individuals with long COVID vs 24 age-matched healthy controls (linear mixed effects model, P = 4 × 10^-5; vs 43 controls, P = 6 × 10^-4). Apathy, motor slowing (secondary outcomes) and memory decline (exploratory outcome) correlated with lower (+)[¹¹C]DTBZ BP_ND in ventral striatum, dorsal putamen and caudate, respectively (|r| = 0.48-0.58, P = 0.0029-0.018). Findings of reduced VMAT2 binding may reflect reduced dopaminergic terminal integrity in long COVID. Loss of dopamine nerve terminals may be contributing to symptom correlates of apathy, motor slowing and memory decline suggesting improved function of dopaminergic synapses as a new therapeutic direction to treat long COVID. Canadian Institutes of Health Research (191851).