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Multicolor Flow Cytometry Analyses of Cellular Immune Response in Rhesus Macaques
Published on: April 22, 2010
Inflammation from mild COVID-19 results in persistent neurological and behavioral changes in rhesus macaques
Tomas R Wiche Salinas1, Sienna Freeman1, Rebecca Richardson1
1Emory National Primate Research Center, Emory University, 954 Gatewood Rd NE, Atlanta GA 30329, USA.
Abstract:
Although most SARS-CoV-2 infections result in mild or moderate symptoms not requiring hospitalization, many patients experience persistent symptoms after their initial recovery, a condition termed Post-Acute Sequelae of SARS-CoV-2 infection (PASC). The underlying pathogenesis behind infection associated chronic illnesses, such as PASC, are poorly understood, thus critically limiting the development of therapeutics to prevent or alleviate symptoms. The current study examined the neurocognitive impact of SARS-CoV-2 induced inflammation in a nonhuman primate model. Ten adult rhesus macaques (5 female, 5 male) were monitored before, during, and after recovery from a mild COVID-19 illness (SARS-CoV-2 strain 2019-noCoV/USA-WA1/2020). Macaques exhibited persistent alterations in taste and smell, as well as decreased cognitive flexibility up to 3 months post-infection. Female macaques experienced sleep disturbances, greater stress and poorer autonomic function months after SARS-CoV-2 infection. Importantly, the development of these neurocognitive changes were associated with acute cytokine response to infection and increased microglia activation in brain tissue at 4 months post-infection. These findings suggest a causative link between the inflammatory response to mild COVID-19 symptoms and persistent neurocognitive changes associated with PASC and provide rationale for therapeutic strategies aimed at reducing acute inflammatory responses to the virus.
Insights
Mild COVID-19 can cause long-term neurocognitive issues like altered senses and cognitive flexibility. This study in macaques links these persistent symptoms to the initial inflammatory response and brain changes.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Post-Acute Sequelae of SARS-CoV-2 infection (PASC) presents persistent symptoms after mild COVID-19.
- The mechanisms driving PASC, particularly neurocognitive impacts, remain poorly understood.
- Limited therapeutic options exist due to gaps in understanding PASC pathogenesis.
Purpose of the Study:
- To investigate the neurocognitive effects of SARS-CoV-2 infection-induced inflammation.
- To explore the link between acute inflammatory responses and long-term neurocognitive sequelae.
- To utilize a nonhuman primate model for studying PASC-related neuroinflammation.
Main Methods:
- Ten adult rhesus macaques (5 female, 5 male) were infected with SARS-CoV-2 (strain 2019-noCoV/USA-WA1/2020).
- Subjects were monitored before, during, and up to 3-4 months post-infection for neurocognitive and physiological changes.
- Brain tissue was analyzed for microglia activation post-infection.
Main Results:
- Macaques showed persistent deficits in taste, smell, and cognitive flexibility up to 3 months post-infection.
- Female macaques experienced sleep disturbances, increased stress, and impaired autonomic function.
- Neurocognitive changes correlated with acute cytokine responses and increased microglia activation in the brain.
Conclusions:
- Mild SARS-CoV-2 infection can lead to lasting neurocognitive alterations.
- An acute inflammatory response to SARS-CoV-2 is linked to persistent neurocognitive deficits.
- Targeting acute inflammatory pathways may offer therapeutic strategies for PASC.
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