Profound Neuroinflammation Is Associated With Long COVID Pathophysiology

Eileen Gamagami, PhD, for Medscape

June 09, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaway

  • In-vivo evidence of widespread neuroinflammation using a quantitative assessment, [18F]DPA-714 PET, implicates profound neuroinflammation in the pathophysiology of long COVID.

Why This Matters

  • Severe neurologic symptoms can persist long after COVID respiratory infection; however, the pathophysiology and long-term effects of 'long COVID' are unknown.

  • This study reports that significant and extensive in-vivo neuroinflammation, measured by [18F]DPA-714 PET, is associated with long COVID.

Study Design

  • Two patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020 and suffered from long COVID were included in this study, one woman in her late 50s and one man in his mid-60s.

  • Both patients with long COVID were declared unfit for work, either partially or totally, and experienced severe fatigue and concentration deficits; additionally, the female suffered from anosmia, parosmia, headaches, and some visual complaints.

  • Both patients were determined to be high affinity binders of the PET tracer by [18F]DPA-714.

  • Three healthy control individuals who had not been infected with SARS-CoV-2 were included in this study, and eight patients with MS were used for comparison of [18F]DPA-714 metabolism.

  • Imaging was conducted using MRI on a 3.0T whole-body scanner. The scanning protocol included a high resolution 3DT1-weighted magnetization prepared rapid acquisition gradients-echo (MP-RAGE) image.

  • Dynamic 60 minute [18F]DPA-714 PET scans with arterial blood sampling were acquired on the same Ingenuity TF PET-CT scanner.

  • Blood concentration levels of [18F]DPA-714 metabolites were assessed and[18F]DPA-714 binding in whole brain gray matter was measured using a plasma input two-tissue compartment model with blood volume parameter (2T4k_VB) for the two long COVID patients compared with all other subjects available.

Key Results

  • Neuropsychological tests and questionnaire scores indicated that long COVID patient 1 had verbal memory deficits, mildly impaired attention, presence of severe fatigue and concentration problems, and severe functional impairment. Long COVID patient 2 had visuo-constructive deficits, fluctuating sustained attention, presence of fatigue, severe concentration problems, and severe functional impairment.

  • Long COVID patient 1 had elevated [18F]DPA-714 binding in all brain regions and whole brain gray matter quantitative measures of binding (BPND values) were increased on average 121% relative to the healthy control subjects.

  • Long COVID patient 2 also had elevated [18F]DPA-714 binding, with an increase in whole brain gray matter BPND values on average 76% relative to the healthy control subjects.

Limitations

  • Only 2 patients with long COVID were included in the study.

  • No comparable neuropsychological or questionnaire data were available.

Disclosures

  • This study was funded by a ZonMw grant (number: 10430302110003).

  • Authors have disclosed a consultancy agreement with IXICO for the reading of PET scans and involvement in investigator-initiated sponsored research with Heuron Co., Ltd. Author(s) received research support from EU-FP7, CTMM, ZonMw, NWO and Alzheimer Nederland, performed contract research for Rodin, IONIS, AVID, Eli Lilly, UCB, DIAN-TUI and Janssen, and received financial compensation from Amsterdam UMC.

This is a summary of a preprint research study, "Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET," written by Denise Visser from the Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, Vrije University Amsterdam, the Netherlands, and colleagues on medRxiv.org, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found medRxiv.org.

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