Imaging neuroglial mechanisms of neuropathic pain-opioid interaction in HIV

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PROJECT SUMMARY/ABSTRACT Since the World Health Organization declared COVID-19 a pandemic in March 2020, increasing evidence shows that COVID-19 affects multiple organs, including the central nervous system (CNS). Effects of COVID- 19 on the CNS have been well documented in the hospitalized setting by magnetic resonance imaging (MRI) and spectroscopy (MRS), blood and cerebrospinal fluid biomarkers and autopsy. Neurological problems associated with COVID-19 can persist long past recovery from the initial stages of COVID-19, including fatigue, cognitive blunting, and body pain which are among the top 10 symptoms reported by COVID-19 survivors. According to the Center for Disease Control, people with HIV (PWH) may be at higher risk for severe outcomes from COVID-19, and the long-term neurological sequelae in this population is unknown and may represent a clinical phenotype at risk for future health threats (i.e., development of cognitive disorders). Data informing the underlying biology of prolonged symptoms in COVID-19 is limited, and how COVID-19 and HIV may interact to affect neurological function is urgently needed. Based on the clinical presentation of COVID-19, complications ranging from mild-to-severe, and known triggers of cerebral pathology, neuroinflammation (Aim 1) and loss of neuronal integrity (Aim 2) are expected to be important components of post-acute sequalae of COVID (PASC). To evaluate neuro-glial dysregulation in people with PASC, we will use advanced brain imaging technologies, neuropsychological testing, fatigue measurements and quantitative sensory testing (QST). Specifically, integrated [11C]PBR28 Positron Emission Tomography / Magnetic Resonance (PET/MR) and 3-Tesla proton magnetic resonance spectroscopy (1H MRS) will be used to evaluate brain levels of glial markers (18kDa translocator protein, TSPO, and myo-inositol, mI), and neuronal / structural integrity markers (N- acetylaspartate, NAA). QST techniques will assess pain threshold, suprathreshold sensitivity and temporal summation, while cognitive function will be assessed using detailed neuropsychological battery designed for COVID-19 patients to assess concentration and attention. People with persistent neurological symptoms after COVID-19 will be enrolled for this supplemental award. The parent R01 will provide two comparator control populations that include people with and without HIV who were not previously infected with COVID-19. Group differences in magnetic resonance markers of neuroinflammation and neuronal integrity and their associations with neurological symptoms including cognitive function and pain will be investigated. The mechanistic insights provided by this supplemental study in HIV-COVID-19 interaction will inform the care and neurological management of people with COVID-19, including PWH, and who are expected to suffer long-term consequences of the pandemic for years to come.