A small case-control study has revealed that an index of gliosis was associated with persistent neurocognitive symptoms after mild or moderate SARS-CoV-2 infection. Researchers found that PET measures of translocator protein total distribution volume (TSPO VT), a marker of gliosis, were elevated in people with ongoing cognitive and depressive symptoms after COVID-19. In comparison to healthy controls, people with post-COVID neurocognitive symptoms and the slowest finger-tapping speeds had higher dorsal putamen TSPO volume than healthy persons by 27%. Increased TSPO expression was found to be particularly prominent in the ventral striatum and dorsal putamen.
This study is the first to evaluate brain gliosis in long COVID, also known as post-acute sequelae of SARS-CoV-2 infection. According to the researchers, these findings have important implications for understanding the pathology of COVID-DC (depressive or cognitive symptoms after acute mild or moderate SARS-CoV-2) and for developing clinical interventions.
The Role of Microglial Activation in Persistent Neuropsychiatric Symptoms After COVID-19
The mechanism behind persistent neuropsychiatric symptoms after COVID-19 remains somewhat of a mystery. Alexander Gerhard, MD, of the University of Manchester in England, observed that up to 20% of individuals might experience cognitive impairment 12 or more weeks following COVID-19 diagnosis. It is therefore necessary to understand the underlying pathophysiology in order to develop potential therapeutic avenues.
Microglial activation is part of the neuroinflammatory response of the brain and can occur in response to a direct insult to the brain, including viral infection. It can also occur following respiratory inflammation and may play an important role in the development of cognitive problems after COVID-19 infection. This study has “important pilot character, as it elucidates a possible mechanism behind neurocognitive symptoms after COVID-19 infection,” Gerhard said.
However, Gerhard also noted that the PET signal for this and other TSPO tracers is particularly noisy and is not limited to microglial cells. Additionally, TSPO expression is only one part of the complex neuroinflammatory response of the brain. “To target neuroinflammatory changes therapeutically, we will need a much more detailed understanding of microglial activation at different time points of neurological disorders,” Gerhard stated. “Not surprisingly, relatively simplistic attempts to suppress microglial activation have so far not resulted in clinically meaningful results.”
The study evaluated 40 people with a mean age of 33, 60% of whom were women. Half had depressive or cognitive symptoms after acute mild or moderate COVID, and half were healthy controls. To qualify for the study, people with COVID-DC had to have a new major depressive episode within three months of acute mild or moderate COVID-19 illness. Healthy controls had no history of psychiatric illness. Prominent symptoms of COVID-DC were anhedonia, motor speed slowing, energy problems, and cognitive concerns.
The mechanisms for neurocognitive symptoms after COVID-19 may be heterogeneous, and outcomes may differ after severe SARS-CoV-2 infection. The researchers also acknowledged that elevated TSPO expression is not completely specific to glial cells. Although most TSPO in neuropsychiatric disease is typically expressed in microglia, and to a lesser extent in astroglia, the next most common cellular expression is in endothelial cells. However, endothelial cell content is unlikely to fully account for the findings.