Long-term COVID cognition, depressive symptoms linked to brain inflammatory markers

Gliosis index was associated with persistent neurocognitive symptoms after mild or moderate SARS-CoV-2 infection in a small case-control study.

Compared to healthy controls, the PET-measured total volume of distribution of translocated proteins (TSPO V_T) is glial A marker of hyperplasia, elevated in people with persistent cognitive and depressive symptoms post-COVID-19 (mean percentage difference 17%), University of Toronto MD Jeffrey Meyer and co-authors report.

TSPO expression increased significantly in the ventral striatum (mean percent difference 26%) and dorsal putamen (mean percent difference 24%), Meyer and colleagues in JAMA Psychiatry

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Movement speed of finger tapping test is negatively correlated with dorsal putamen TSPO volume (r – 0.53, 95% CI -0.79 to -0.09). People with post-COVID neurocognitive symptoms and the slowest finger tapping speed had 27% higher dorsoputamen TSPO volumes than healthy people.

The study is the first to assess brain gliosis in long COVID, also known as the acute sequelae of SARS-CoV-2 infection, Meyer and coauthors said. “We focused our sample on common clinical phenomena representing depressive or cognitive symptoms after acute mild or moderate SARS-CoV-2 (COVID-DC),” they wrote.

“We found generalized differences in TSPO V_T between COVID-DC patients and healthy control participants, most prominently in the ventral striatum and dorsal putamen , and the severity of motor slowing was associated with higher dorsoputamen TSPO V_T,” they added. “These findings have important implications for understanding the pathology of COVID-DC and developing clinical interventions.”

University of Manchester, UK, in an accompanying editorial.

“As up to 20% of individuals may experience cognitive impairment 12 weeks or more after a COVID-19 diagnosis, it is of paramount importance to understand the underlying pathophysiology in order to develop potential therapeutic avenues,” Gerhard wrote. “Microglial activation as part of the brain’s neuroinflammatory response can occur in response to direct injury to the brain, including viral infection, but can also occur after airway inflammation and may play an important role in the development of cognitive problems after infection post-COVID-19.”

Gerhard said the study is “important in its experimental nature as it elucidates possible mechanisms underlying neurocognitive symptoms following COVID-19 infection”.

“While this is an important piece of the neuroinflammation puzzle in chronic neurological disease, it is important to remember that our understanding of the complex is still lacking for a number of reasons,” he pointed out.

Gerhard noted that the PET signal of this and other TSPO tracers is particularly noisy and not limited to microglia. Furthermore, TSPO expression is only one part of the brain’s complex neuroinflammatory response.

“In order to therapeutically target neuroinflammatory changes, we need a more detailed understanding of microglial activation at different time points in neurological diseases,” Gerhard said. “Not surprisingly, relatively simple attempts to suppress microglial activation have so far yielded no clinically meaningful results.”

Meyer and coauthors evaluated 40 individuals with an average age of 33 year-old; 60% are women. Half had depressive or cognitive symptoms after acute mild or moderate COVID and half were healthy controls. The study will be conducted in Canada from April 2021 to June 2022.

To be eligible for the study, individuals with COVID-DC must be in acute mild or moderate COVID-19 disease. The healthy control group had no history of mental illness. Prominent symptoms of COVID-DC are anhedonia, slowed movement, energy issues, and cognitive issues.

Mechanisms of neurocognitive symptoms after COVID-19 may be heterogeneous and outcomes may be different after severe SARS-CoV-2 infection, note Meyer and coauthors.

Furthermore, the researchers acknowledge that elevated TSPO expression is not entirely specific to glial cells. “Although the majority of TSPO in neuropsychiatric disorders is commonly expressed in microglia and, to a lesser extent, astrocytes, the next most common cell expressed is in endothelial cells,” they said wrote. “However, endothelial cell content is unlikely to fully explain these findings.”

Judy George covers neurology and neuroscience news for MedPage Today and writes about brain aging, Alzheimer’s, dementia, multiple sclerosis, rare diseases, epilepsy, autism, headaches, stroke, Parkinson’s , Amyotrophic lateral sclerosis, concussion, CTE, sleep, pain, etc. Follow