Neuronal and Glial Metabolite Abnormalities in Participants with Persistent Neuropsychiatric Symptoms after COVID-19: A Brain Proton Magnetic Resonance Spectroscopy Study

Abstract

Background: The aim of this study was to determine whether neurometabolite abnormalities indicating neuroinflammation and neuronal injury are detectable in individuals post-coronavirus disease 2019 (COVID-19) with persistent neuropsychiatric symptoms. Methods: All participants were studied with proton magnetic resonance spectroscopy at 3 T to assess neurometabolite concentrations (point-resolved spectroscopy, relaxation time/echo time = 3000/30 ms) in frontal white matter (FWM) and anterior cingulate cortex-gray matter (ACC-GM). Participants also completed the National Institutes of Health Toolbox cognition and motor batteries and selected modules from the Patient-Reported Outcomes Measurement Information System. Results: Fifty-four participants were evaluated: 29 post-COVID-19 (mean ± SD age, 42.4 ± 12.3 years; approximately 8 months from COVID-19 diagnosis; 19 women) and 25 controls (age, 44.1 ± 12.3 years; 14 women). When compared with controls, the post-COVID-19 group had lower total N-Acetyl compounds (tNAA; ACC-GM:-5.0%, P =. 015; FWM:-4.4%, P =. 13), FWM glutamate + glutamine (-9.5%, P =. 001), and ACC-GM myo-inositol (-6.2%, P =. 024). Additionally, only hospitalized patients post-COVID-19 showed age-related increases in myo-inositol, choline compounds, and total creatine (interaction P =. 029 to