A significant number of COVID-19 patients develop 'long COVID', a condition defined by long-lasting debilitating, often neurological, symptoms. The pathophysiology of long COVID is unknown. Here we present in-vivo evidence of widespread neuroinflammation in long COVID, using a quantitative assessment, [18F]DPA-714 PET, in two long COVID patients. We reanalyzed historical data from three matched healthy control subjects, for comparison purposes. Both patients with long COVID had widespread increases in [18F]DPA-714 binding throughout the brain. Quantitative measures of binding (BPND values) were increased on average by 121% and 76%, respectively. This implicates profound neuroinflammation in the pathophysiology of long COVID.
### Competing Interest Statement
EG has a consultancy agreement with IXICO for the reading of PET scans and is involved in investigator-initiated sponsored research with Heuron Co., Ltd. FB is member of the Radiology editorial board. AW is editor-in-chief of Nuclear Medicine and Biology. BB has received research support from EU-FP7, CTMM, ZonMw, NWO and Alzheimer Nederland. BvB has performed contract research for Rodin, IONIS, AVID, Eli Lilly, UCB, DIAN-TUI and Janssen. BvB was a speaker at a symposium organized by Springer Healthcare. BB has a consultancy agreement with IXICO for the reading of PET scans. BB is a trainer for GE. BB only receives financial compensation from Amsterdam UMC. No other potential conflicts of interest were reported.
### Clinical Trial
### Funding Statement
This study was funded by a ZonMw grant (number: 10430302110003)
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This study was approved by the Medical Ethics Review Committee of the Amsterdam UMC, location VU Medical Center, and registered under 2021-000781-15 in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) and under [NCT05371522] in ClinicalTrials.gov.
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