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 NCT05371522 ### Funding Statement This study was funded by a ZonMw grant (number: 10430302110003) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: 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][1] in ClinicalTrials.gov. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05371522&atom=%2Fmedrxiv%2Fearly%2F2022%2F06%2F04%2F2022.06.02.22275916.atom
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