Does Microglial Activation Lead to Cognitive Changes After COVID-19 Infection?

Abstract

One of the many issues we have yet to understand in relation to the COVID-19 pandemic is the mechanism by which the infection can cause long-lasting neuropsychiatric symptoms, particularly cognitive symptoms and depression as part of the postacute period, referred to as post-COVID-19 condition (also known as long COVID). Since as many as 20% of individuals might experience cognitive impairment 12 or more weeks following COVID-19 diagnosis, 1 it is paramount to understand the underlying pathophysiology in order to develop potential therapeutic avenues. Microglial activation as part of the neuroinflammatory response of the brain can occur as an answer to a direct insult to the brain (this includes viral infection) but can also occur following respiratory inflammation and might play an important role in the development of cognitive problems after COVID-19 infection. 2 Braga et al 3 present elegant work on this matter. They have examined the in vivo neuroinflammatory changes in patients with persistent depressive and cognitive symptoms after COVID-19 infection using positron emission tomography (PET) and the ligand [ 18 F]FEPPA for the translocator protein 18 kDa (TSPO), which is expressed by activated microglia as part of the neuroinflammatory response of the brain.They found an increased expression of TSPO in patients with persistent neurocognitive symptoms after COVID-19 infection compared to healthy control individuals, especially in the ventral striatum and dorsal putamen. TSPO binding in the dorsal putamen of individuals with post-COVID-19 conditions negatively correlated with speed in motor tasks.These findings indicate that microglial activation was associated with the development of neurocognitive symptoms after COVID-19 infection and the imaging technique the authors used has the advantage that it allows the imaging of this part of the neuroinflammatory process in vivo. The authors conclude that increased microglial activation in the ventral striatal and dorsal putamen reflects a possible mechanism to explain persistent depressive cognitive symptoms after COVID-19 infection.