ABSTRACT
Aim/Introduction: A substantial amount of post-COVID-19 patients suffer from debilitating fatigue and cognitive impairment persisting months after infection, referred to as 'long COVID'. The pathophysiology of long COVID is unknown, but post-mortem studies have demonstrated that after acute SARS-CoV-2 infection profound neuro-inflammation may be present. However, to date no clear in-vivo evidence for this is available in patients who survived COVID-19. The aim of this study was to quantify neuro-inflammation in-vivo with [18F]DPA-714 positron emission tomography (PET) in post COVID patients with and without long term complaints. [18F] DPA-714 binds with high affinity to translocator protein (TSPO) that is brought to expression on, among others, activated microglia, enabling visualization of neuro inflammation in-vivo. Material(s) and Method(s): We will include patients with and without persisting postinfectious fatigue, cognitive complaints and smell loss or distortions and will relate it to cognitive, psychiatric and post infectious fatigue symptoms. We will assess in-vivo peripheral and neuro-inflammation with a 90 minutes [18F]DPA-714 PET scan, alternately capturing brain (dynamic 60 minutes) and body (30 minutes;pelvic to head) with both continuous on-line and manual arterial blood sampling for full quantification. The 30-minutes body scan will be performed to examine whole-body inflammation (secondary parameter). Brain MRI will be performed for functional and anatomical information. Additionally, neuropsychological assessment and questionnaires will be performed. So far, we included five patients with long COVID with persisting post-infectious fatigue and cognitive complaints, who all got infected in 2020. Two patients were female and patients were on average 59 +/- 5 years of age. Indeed, this is an ongoing study and more data (>20 patients) will become available in the near future. Result(s): We will report on the first results of this crosssectional observational case-control study in which we quantify peripheral and neuro-inflammation with fully quantitative [18F] DPA-714 PET scans in post-COVID-19 patients. Preliminary results indicate profound neuro-inflammation in these first patients with long COVID. Conclusion(s): Preliminary results of this study indicate that patients with long COVID have profound neuro-inflammation. Results of this study may provide important insight into the underlying pathophysiology of long COVID symptoms and may potentially provide opportunities for future (treatment-directed) studies.
ABSTRACT
Aim/Introduction: A hallmark of coronavirus disease 2019 (COVID-19) is lower respiratory tract infection and pneumonia. Infection of nonhuman primates mirrors mild-to-moderate human disease determined with concordant immunologic, virologic, and lung histopathologic findings in combination with imaging abnormalities. Particularly in the lower respiratory tract, medical imaging of pulmonary disease contributes uniquely to the understanding and measuring of the consequences of an infection. Advanced medical imaging, such as PET-CT, of the lungs of SARS-CoV-2-exposed nonhuman primates shows great promise in detecting and longitudinally evaluating disease in a non-invasive manner. The aim of this study was to investigate the application of [18F]DPA714 for visualizing the inflammation processes in the lungs of SARS-CoV-2-infected rhesus monkeys. Material(s) and Method(s): Four experimentally SARS-CoV-2 infected rhesus monkeys were followed for seven weeks post infection (pi) with a weekly PETCT using a MultiScan Large Field of View Extreme Resolution Research Imager (LFER) 150 (Mediso Medical Imaging Systems Ltd., Budapest, Hungary) with [18F]DPA714 as radiotracer. Following a retrospectively gated CT, an intravenous bolus of approximately 180 MBq [18F]DPA714 (molar activity: 77.4 GBq/mumol (range 39.8- 150.6 GBq/mumol, radioactivity concentration: of 277.0+/-172.8 MBq/ mL, a radiochemical purity > 98.0%) was administered. Two PET images, ten minutes each, of a single field-of-view covering the chest area, were obtained ten and thirty minutes after injection. To confirm the infection of SARS-CoV-2 , both nasal and tracheal swabs and blood samples were obtained. Result(s): All animals tested positive for SARS-CoV-2 in both swabs on multiple timepoints pi. The initial development of pulmonary lesions was already detected at the first scan 2-days pi. PET revealed an increased tracer uptake in the pulmonary lesions and mediastinal lymph nodes of all animals starting from the first scan pi onwards. However, also an increased uptake was detected in the lung tissue surrounding the lesions, which persisted until day 30 and then subsided by day 37-44 pi. In parallel, a similar pattern of increased expression of activation markers was observed on dendritic cells in blood. Conclusion(s): This study illustrates that [18F]DPA714 is a valuable radiotracer to visualize SARS-CoV-2-associated pulmonary inflammation even during mild-to-moderate disease. In addition, the inflammatory process detected in anatomically unaffected lung tissue coincided with dendritic cell activation detected in blood samples. Our data indicate that [18F]DPA714 can be applied to visualize the pulmonary tract following a SARS-CoV-2 infection in rhesus monkeys and may be translated to the clinic as diagnostic tracer for this indication too.