Objective:

This study aimed to investigate clinical symptoms combined with biological data including images and blood samplings for revealing pathological mechanism of neuropsychological long COVID.

Background:

Although most patients can recover from COVID-19 acute phase, some will suffer from depression, insomnia, concentration problems, fatigue, and cognitive decline, i.e. “brain fog” or neuropsychological long COVID. However, the mechanism of neuropsychological long COVID is not well investigated. Moreover, biomarkers which can objectively assess these symptoms have not been established.

Design/Methods:

Between March 2023 and February 2024, patients who met the criteria of “brain fog” screening questionnaire (fatigue, diminished concentration, confusion, insomnia, memory loss, language impairment, visual impairment, vertigo, and appetite loss) with informed consent were enrolled in this study (n=33, female 16, average[SD] age 38.5[14.8]). All participants were examined with blood biomarkers (amyloid β-42/40 [Aβ42/40], pTau, GFAP, Neurofilament light chain [NfL]), MRI, and single-photon emission computed tomography (SPECT). Z-score of regional cerebral blood flow (rCBF), calculated from SPECT, was used for the indicator of decreased neuronal activity. Relationship between symptoms and biomarkers was evaluated by multiple regression analysis.

Results:

Fatigue, diminished concentration, and memory loss were major complaints (81.8%, 60.6%, and 48.5%, respectively). Significant correlations were observed between insomnia and Aβ42/40 (r=0.474: p=0.019), language impairment and NfL (r=0.504: p=0.012), and appetite loss and Aβ42/40 (r=0.459: p=0.024). There were significant relations between hypoactive brain regions and symptoms i.e. left occipital lobe and insomnia (p=0.004), right occipital lobe and memory loss (p=0.036), left temporal lobe or both-side limbic system and language impairment (p=0.003, p=0.010 [left] and p=0.049 [right], respectively), and left limbic system or pons and appetite loss (p=0.038 and p=0.044, respectively).

Conclusions:

Neuropsychological symptoms after COVID-19 infection can be assessed by blood biomarkers and SPECT with evidence of significant neuronal damage. Since specific brain lesions associated to symptoms, our findings may shed light on the underlying pathomechanism.