The Journal of infectious diseasesAug 4, 2023

Abnormal Brain Cell Metabolites in People with Ongoing Neuropsychiatric Symptoms After COVID-19

Updated Jan 13, 2026

Abstract

Post-COVID-19 individuals exhibited lower total N-acetyl compounds in frontal white matter and anterior cingulate cortex compared to controls.

The post-COVID-19 group had decreased levels of total N-acetyl compounds in the anterior cingulate cortex (5.0% lower) and frontal white matter (4.4% lower).
Significantly lower levels of glutamate + glutamine were observed in frontal white matter (9.5% lower) among post-COVID-19 participants.
Myo-inositol levels were also lower in the anterior cingulate cortex (6.2% lower) for the post-COVID-19 group compared to controls.
Hospitalized post-COVID-19 patients demonstrated age-related increases in myo-inositol, choline compounds, and total creatine.
Lower levels of frontal white matter total N-acetyl compounds and higher anterior cingulate cortex myo-inositol correlated with poorer cognitive performance.
A decrease in anterior cingulate cortex total N-acetyl compounds was associated with reduced endurance in the 2-minute walk test.

Simplified

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 <.001). Across all participants, lower FWM tNAA and higher ACC-GM myo-inositol predicted poorer performance on several cognitive measures (P = .001-.009), while lower ACC-GM tNAA predicted lower endurance on the 2-minute walk (P = .005).

CONCLUSIONS: In participants post-COVID-19 with persistent neuropsychiatric symptoms, the lower-than-normal tNAA and glutamate + glutamine indicate neuronal injury, while the lower-than-normal myo-inositol reflects glial dysfunction, possibly related to mitochondrial dysfunction and oxidative stress in Post-COVID participants with persistent neuropsychiatric symptoms.

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Competing interests

Potential conflicts of interest. S. K. is a member of the Scientific Advisory Board at Merck, Regeneron, Silverback Therapeutics, Zhuhai Yufan Biotechnologies, and The Liver Company and has received grants paid to the institution from Gilead Sciences and Arbutus Pharmaceuticals. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

PubMed

Abnormal Brain Cell Metabolites in People with Ongoing Neuropsychiatric Symptoms After COVID-19

Abstract

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Competing interests

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Abstract

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