Ongoing oxidative stress in individuals with post-acute sequelae of COVID-19

Muhammad G Saleh; Linda Chang; Huajun Liang; Meghann C Ryan; Eric Cunningham; Jonathan Garner; Eleanor Wilson; Andrea R Levine; Shyamasundaran Kottilil; Thomas Ernst

doi:10.1515/nipt-2022-0006

Ongoing oxidative stress in individuals with post-acute sequelae of COVID-19

NeuroImmune Pharm Ther. 2022 Aug 15;2(2):89-94. doi: 10.1515/nipt-2022-0006. eCollection 2023 Jun.

Authors

Muhammad G Saleh¹, Linda Chang^{1

2

3}, Huajun Liang¹, Meghann C Ryan¹, Eric Cunningham¹, Jonathan Garner¹, Eleanor Wilson⁴, Andrea R Levine⁵, Shyamasundaran Kottilil⁴, Thomas Ernst^{1

3}

Affiliations

¹ Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
² Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.
³ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Medicine, Division of Infectious Disease, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁵ Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

Objectives: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with lower plasma glutathione (GSH) levels due to oxidative stress. However, plasma levels may not reflect brain GSH levels. Individuals with post-acute sequelae of COVID-19 (PASC) have a higher prevalence of cognitive fatigue, which might be related to altered brain γ-aminobutyric-acid (GABA) levels. Hence, our study aims to measure the brain GSH and GABA levels in PASC.

Methods: 29 PASC participants and 24 uninfected controls were recruited for this study. Each was evaluated with detailed neuropsychiatric assessments and an edited proton MRS (Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy, HERMES) method to measure GABA and GSH concentrations in predominantly grey matter (GM) and predominantly white matter (WM) brain frontal voxels.

Results: PASC participants were 219 ± 137 days since their COVID-19 diagnosis. Nine individuals with PASC were hospitalized. Compared to controls, individuals with PASC had similar levels of GABA in both brain regions, but lower GSH and greater age-related GSH decline in the frontal GM region.

Conclusions: The lower-than-normal frontal GM GSH level in participants with PASC suggest that they have ongoing oxidative stress in the brain, and that older individuals may be even more vulnerable to oxidative stress.

Keywords: COVID-19; GABA; SARS-CoV2; glutathione.

Abstract

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