Irrespective of whether a person has ever been infected with the SARS-Cov-2 virus or not, one thing is for sure: it affected the mental health of every individual.

New research has indicated that for some individuals even those who have steered clear of becoming infected with SARS-CoV-2 -- societal and lifestyle disruptions during the COVID-19 pandemic may have triggered inflammation in the brain that can affect mental health. The study, which was conducted by a team led by investigators at Massachusetts General Hospital (MGH), is published in Brain, Behavior, and Immunity.

Beyond causing a staggering number of infections and deaths, the COVID-19 pandemic has led to significant social and economic disruptions that have impacted the lives of a large swath of the world's population in multiple ways. Also, since the start of the pandemic, the severity and prevalence of symptoms of psychological distress, fatigue, brain fog, and other conditions increased considerably in the United States, including among people not infected with SARS-CoV-2.

To obtain a better understanding of the effects of the pandemic on the brain and mental health, researchers analysed brain imaging data, conducted behavioural tests, and collected blood samples from multiple uninfected volunteers -- 57 before and 15 after lockdown/stay-at-home measures were implemented to limit the pandemic's spread.

After lockdowns, the study participants demonstrated elevated brain levels of two markers of neuroinflammation -- translocator protein (measured using positron emission tomography) and myoinositol (measured using magnetic resonance spectroscopy) -- compared with pre-lockdown participants. Blood levels of two inflammatory markers -- interleukin-16 and monocyte chemoattractant protein-1 -- were also elevated in post-lockdown participants, although to a lesser extent.

Participants who reported a higher burden of symptoms related to mood and mental and physical fatigue showed higher levels of translocator protein in certain brain regions, compared with those reporting little or no symptoms. Also, higher post-lockdown translocator protein levels correlated with the expression of several genes involved in immune functions.

"While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected has remained under-explored," said lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at MGH and Harvard Medical School.

"Our study demonstrates an example of how the pandemic has impacted human health beyond the effects directly caused by the virus itself." Senior author Marco L. Loggia, PhD, co-director of the Center for Integrative Pain NeuroImaging at MGH and Harvard Medical School noted that acknowledging a role of neuroinflammation in the symptoms experienced by many during the pandemic might point to possible strategies to reduce them.

"For instance, behavioural or pharmacological interventions that are thought to reduce inflammation -- such as exercise and certain medications -- might turn out to be helpful as a means of reducing these vexing symptoms". Loggia added that the findings also provided further support to the notion that stressful events might be accompanied by brain inflammation. "This could have important implications for developing interventions for a broad number of stress-related disorders," he said.