Research finds increases in 'pandemic brain' after COVID-19 lockdowns
Chances are, the COVID-19 pandemic has affected your health — even if you have never been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to new research from Harvard Medical School, the stress of isolation from lockdown and stay-at-home measures is making people sick. Their medRxiv* study suggests people not infected with SARS-CoV-2 are experiencing increased markers of neuroinflammation, otherwise known as "pandemic brain."
Neuroinflammation is associated with mood disorders such as depression. In addition, neuroimmune changes are characterized by fatigue, brain fog, and other psychological symptoms that have been observed during the pandemic.
How they did it
The researchers examined the brains of healthy and non-infected individuals before (n = 57) or after lockdown (n=15) in Massachusetts. To start, the team gave out a questionnaire that would evaluate a participant's mental and physical health during the pandemic. Then, brain imaging was performed to identify any markers of neuroinflammation.
Pandemic-associated stressors trigger changes in the neuroimmune response
People were more likely to report more issues with their mental and physical health after lockdown. For example, about 54% reported mood changes, 36% felt mentally exhausted, 27% were physically exhausted, and 18% said they had difficulty concentrating.
The symptoms mentioned above coincided with an increase in [11C]PBR28 signal, a radioactive biochemical substance for the glial marker 18 kDa translocator protein (TSPO). High expression of TSPO is associated with the activation of microglia and astrocytes during a neuroinflammatory response. Additionally, the signal elevation was higher in people's brains after lockdown than before lockdown.
For brains imaged after lockdown, there was an increase in the brain levels of [11C]PBR28 in several cortical and subcortical regions. The brain regions included precentral, postcentral, superior, middle, and inferior frontal gyri, precuneus, superior parietal lobule, anterior and posterior insula, amygdala, putamen, supplementary motor cortex, anterior, middle, posterior cingulate, and subcallosal cortex.
The [11C]PBR28 signal was more elevated in people who reported more symptoms than those who reported little or no symptoms. Increased markers associated with neuroinflammation were present in participants who reported physical fatigue. Mental fatigue or mood changes were associated with [11C]PBR28 signal changes in the hippocampus.
The [11C]PBR28 signal changes after lockdown parallel changes in gene expression in cells involved in neuroinflammation.
Two genes, AQP4 and CSF1R, were highly expressed in glial cells such as astrocytes and microglia. The monocyte marker CCR1 also showed increased expression. The increased gene expression was related to biological pathways for neuroimmune signaling.
"Collectively, these findings provide support to neuroimmune responses as mechanisms underlying stress, depression and other symptoms of psychological distress. Further, the regional variability in increased [11C]PBR28 signal could be predicted by constitutive expression of genes related to glial neuroimmune response in healthy post-mortem human brains," concluded the researchers.
Several points should be considered when interpreting the study's results. First, since clinical research was temporarily halted during the pandemic, only a small number of participants were available to undergo a brain scan after lockdown compared to people who had brain scans before lockdown.
The researchers did not conduct the questionnaire the same day as the brain scan, leaving the possibility that people may have felt different symptoms at the time of their visit. Therefore, the clinical symptoms collected during the questionnaire will need to be validated in future studies.
Overall, the results indicate that the virus has a broad impact on physical health. In an effort to mitigate infection, pandemic-related lifestyle disruptions may have had indirect consequences on the brain. Future research looking at COVID-19-pandemic–related neuroinflammatory responses is needed to know how this may affect people in the long run.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Brusaferri L, et al. (2021). The Pandemic Brain: neuroinflammation in healthy, non-infected individuals during the COVID-19 pandemic. medRxiv. Doi: https://doi.org/10.1101/2021.09.21.21263740, https://www.medrxiv.org/content/10.1101/2021.09.21.21263740v1
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