Cortical GABA Levels Are Reduced in Post-Acute COVID-19 Syndrome

• Published in: Brain sciences 2023-12, Vol.13 (12), p.1666
• Main Authors: Marinkovic, Ksenija, White, David R, Alderson Myers, Austin, Parker, Katie S, Arienzo, Donatello, Mason, Graeme F
• Format: Article
• Language: English
• Subjects: 1H-MRS; Anxiety; Attention; Cell signaling; Cognition; Cognitive ability; Community; Comparative analysis; Complications; Concussion; Coronaviruses; COVID-19; depression; GABA; Illnesses; Infections; Inflammation; Insomnia; long COVID; Magnetic resonance spectroscopy; Mediation; Mental depression; Metabolism; Metabolites; N-Acetylaspartate; NAA; Neurons; Occipital lobe; Pandemics; Quality of life; Sleep; Spectrum analysis; γ-Aminobutyric acid
• ISSN: 2076-3425; 2076-3425
• DOI: 10.3390/brainsci13121666

After recovering from the acute COVID-19 illness, a substantial proportion of people continue experiencing post-acute sequelae of COVID-19 (PASC), also termed "long COVID". Their quality of life is adversely impacted by persistent cognitive dysfunction and affective distress, but the underlying neural mechanisms are poorly understood. The present study recruited a group of mostly young, previously healthy adults (24.4 ± 5.2 years of age) who experienced PASC for almost 6 months following a mild acute COVID-19 illness. Confirming prior evidence, they reported noticeable memory and attention deficits, brain fog, depression/anxiety, fatigue, and other symptoms potentially suggestive of excitation/inhibition imbalance. Proton magnetic resonance spectroscopy ( H-MRS) was used to examine the neurochemical aspects of cell signaling with an emphasis on GABA levels in the occipital cortex. The PASC participants were compared to a control (CNT) group matched in demographics, intelligence, and an array of other variables. Controlling for tissue composition, biological sex, and alcohol intake, the PASC group had lower GABA+/water than CNT, which correlated with depression and poor sleep quality. The mediation analysis revealed that the impact of PASC on depression was partly mediated by lower GABA+/water, indicative of cortical hyperexcitability as an underlying mechanism. In addition, N-acetylaspartate (NAA) tended to be lower in the PASC group, possibly suggesting compromised neuronal integrity. Persistent neuroinflammation may contribute to the pathogenesis of PASC-related neurocognitive dysfunction.