SARS-CoV-2 RNA persists in the central nervous system of non-human primates despite clinical recovery
Year: 2023
Type: article
Abstract: Adverse neurological and psychiatric outcomes, collectively termed the post-acute sequelae of SARS-CoV-2 infection (PASC), persist in adults clinically recovered from COVID-19. Effective therapeutic interventions are fundamental to reducing the burden of PASC, necessitating an investigation of the pathophysiology underlying the debilitating neurological symptoms associated with the condition. Herein, eight non-human primates (Wild-Caught African Green Monkeys, n =4; Indian Rhesus Macaques, n =4) were inoculated with the SARS-CoV-2 isolate USA-WA1/2020 by either small particle aerosol or via multiple routes. At necropsy, tissue from the olfactory epithelium and pyriform cortex/amygdala of SARS-CoV-2 infected non-human primates were collected for ribonucleic acid in situ hybridization (i.e., RNAscope). First, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) mRNA are downregulated in the pyriform cortex/amygdala of non-human primates clinically recovered from SARS-CoV-2 inoculation relative to wildtype controls. Second, abundant SARS-CoV-2 mRNA was detected in clinically recovered non-human primates; mRNA which is predominantly harbored in pericytes. Collectively, examination of post-mortem pyriform cortex/amygdala brain tissue of non-human primates clinically recovered from SARS-CoV-2 infection revealed two early pathophysiological mechanisms potentially underlying PASC. Indeed, therapeutic interventions targeting the downregulation of ACE2, decreased expression of TMPRSS2, and/or persistent infection of pericytes in the central nervous system may effectively mitigate the debilitating symptoms of PASC.
Source: Molecular Biomedicine
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,258
Awards: G2094357788, G2957582635, Neurobiological Mechanisms of Apathy in HAND, G3925572253, G5189047705, G5514239192, G6075900548, HIV/COCAINE NEUROTOXICITY IN FEMALES, G6510997095, Neurocognitive Impairments Resulting from Adolescent Prescription Opioid Use Disorder: Longitudinal Impact, Neural Mechanisms, and Comorbidities, Progression of Attentional and Executive Function Deficits in HAND, G814809518, G870627805, G9000150658, G9000300598, G9000337672, Neurocognitive Impairments Resulting from Adolescent Prescription Opioid Use Disorder: Longitudinal Impact, Neural Mechanisms, and Comorbidities, Tulane National Primate Research Center
OpenAlex ID: W4388460374