Brainstem neurochemical profiles after hospitalisation for COVID-19: a 7T MR spectroscopy study

Somatic, cognitive and mental health issues have been identified in three-quarters of people 5 months after hospitalisation for severe acute SARS-CoV-2 (COVID-19) infection. The underlying neuroanatomical basis of these symptoms remains unclear, but recent studies suggest a role for altered brainstem physiology. We aimed to test the hypothesis that brainstem neurochemical profiles differ in patients who had been hospitalised for COVID-19 compared to matched controls using 7T magnetic resonance spectroscopy (MRS). This prospective case–control study recruited 34 individuals who were hospitalised for COVID-19 and 15 healthy controls with no history of COVID-19 infection from two major UK hospitals before vaccines became available. The participants underwent 7T semi-adiabatic localization by adiabatic selective refocusing (sLASER) 1H-MRS at the ponto-medullary junction. Water-referenced metabolite concentrations were compared between the patients and controls and correlated with infection severity, as measured by maximum C-reactive protein (CRPmax) assay during inpatient admission. Linear mixed modelling was used with a 0.05 significance level. Spectral quality was high/acceptable in 44/49 participants according to the MRS Consensus criteria. The magnitude of inflammation during patient admission (i.e., CRPmax) correlated positively with myo-inositol concentration (β = 0.005, p = 0.035), as did patient-reported symptoms (β = −0.564, p = 0.023). However, metabolite concentrations were not significantly different between the patients and controls. We show the feasibility of assessing brainstem neurochemical profiles using 7T 1H-MRS in a multi-centre study. Technical limitations at one site’s 7T MRI led to variable repetition times, which limited our statistical power and should be avoided in future studies. Our findings highlight the need for further investigation into the role of neuroinflammation in post-acute COVID-19.

Description

Peer reviewed: True

Acknowledgements: We would like to thank the patients and healthy controls for their participation and the radiographers and research coordinators for their efforts at this difficult time. We thank Dinesh Deelchand for providing a VB17 GOIA semi-LASER package. We thank the NIHR BioResource volunteers for their participation and gratefully acknowledge the Focledge NIHR BioResource centres, NHS Trusts and staff for their contribution. We also thank the National Institute for Health and Care Research, the NHS Blood and Transplant and the Health Data Research UK, as part of the Digital Innovation Hub Programme. The views expressed are those of the author(s) and do not necessarily reflect those of the NHS, the NIHR, the Rosetrees Trust or the Department of Health and Social Care. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Keywords

32 Biomedical and Clinical Sciences, 3202 Clinical Sciences, Emerging Infectious Diseases, Infectious Diseases, Biomedical Imaging, Clinical Research, Coronaviruses, Mental health, 3 Good Health and Well Being

Journal Title

Frontiers in Neuroscience

Journal ISSN

1662-4548
1662-453X

Volume Title

19

Publisher

Frontiers

Publisher DOI

https://doi.org/10.3389/fnins.2025.1617709

Rights and licensing

Except where otherwised noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/

Sponsorship

Wellcome Trust Ltd (098436/Z/12/Z)
Wellcome Trust Ltd (098436/Z/12/B)
Horizon Europe UKRI Underwrite ERC (10032205)
Wellcome Trust (Unknown)
Medical Research Council (MR/M008983/1)
Wellcome Trust (103838/Z/14/Z)
European Commission Horizon 2020 (H2020) Future and Emerging Technologies (FET) (801075)
Wellcome Trust (220258/Z/20/Z)
National Institute for Health Research (NIHR) (via NHS Cambridgeshire and Peterborough Integrated Care Board (ICB)) (OH-BRC NIHR203316)

We were supported by the Addenbrooke’s Charitable Trust, the National Institute for Health and Care Research (NIHR) Cambridge BioResource, by the COVID-19 Clinical Neuroscience Study (COVID-CNS), the Oxford University Medical Sciences Division COVID Rapid Response Fund (reference number 0009118) and by the Medical Research Council [MR/V03605X/1]. This study was supported by the NIHR Cambridge Biomedical Research Centre [NIHR203312] and an MRC Clinical Research Infrastructure Award for 7T research [MR/M008983/1]. This study was supported by the NIHR Oxford Health Biomedical Research Centre (NIHR203316). SC and the Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z and 203139/A/16/Z). CG is supported by the Cambridge Trust, the W.D. Armstrong Fund and the European Union’s H2020 research and innovation program under grant agreement [801075]. BR is funded by a Wellcome Career Development Award fellowship (302210/Z/23/Z). WTC was funded by the Wellcome Trust [225924/Z/22/Z]. VFJN was supported by an Academy of Medical Sciences / The Health Foundation Clinician Scientist Fellowship and is currently supported by an NIHR Rosetrees Trust Advanced Fellowship NIHR302544, which is funded in partnership by the NIHR and Rosetrees Trust. MPC acknowledges support from the Oxford NIHR Biomedical Research Centre. SN acknowledges support from the Oxford NIHR Biomedical Research Centre and from the Oxford BHF Centre of Research Excellence. JBR was supported by the Wellcome Trust [103838; 220258]. CTR was funded by the Wellcome Trust and the Royal Society [098436/Z/12/B].

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