Gray matter atrophy and severe disruption of brain functional connectivity were seen in long COVID patients with anxiety and depression about 3 months after acute mild SARS-CoV-2 infection.
Compared with people who were asymptomatic after SARS-CoV-2 infection, long COVID patients with both anxiety and depression showed limbic atrophy and a widespread pattern of hyperconnectivity, reported Clarissa Yasuda, MD, PhD, of the University of Campinas in São Paulo, Brazil, and colleagues, in an abstract released in advance of the American Academy of Neurology annual meeting.
The magnitude of changes suggest an association with cognitive dysfunction, they observed.
"Our results suggest a severe pattern of changes in how the brain communicates as well as its structure, mainly in people with anxiety and depression with long COVID syndrome, which affects so many people," Yasuda said in a statement. "Our findings are concerning, as even people with a mild case of COVID-19 are showing changes in their brains months later."
The findings add to the growing body of evidence that show brain structure and function are affected by SARS-CoV-2, noted Ziyad Al-Aly, MD, director of the clinical epidemiology center and chief of research and development at the VA St. Louis Health Care System, who wasn't involved with the study.
"Anxiety and depression are manifestations of the neurologic damage caused by SARS-CoV-2 and this abstract provides further objective evidence of structural and functional alteration in the brain following SARS-CoV-2 infection," Al-Aly told MedPage Today. "Our understanding of this is evolving, but clearly infection with SARS-CoV-2 can affect the brain."
Many studies have shown brain problems persist long after acute infection, with some symptoms lasting as long as 2 years, but why this happens isn't clear.
"Some hypothesize that microglia are activated in some people with SARS-CoV-2 and that the inflammatory response that ensues creates a milieu that is disruptive to neuronal health," Al-Aly said. "Other hypotheses revolve around autoimmunity. At this point, we are still learning more and more every day."
Yasuda and colleagues evaluated 254 individuals with mild COVID-19 a median of 82 days from RT-PCR test with Beck Depression Inventory and Beck Anxiety Inventory tests. The overall sample included 177 women with a median age of 41.
Participants were separated into asymptomatic (152 people) and simultaneous (102 people with simultaneous anxiety and depression symptoms based on test scores) groups.
Gray matter atrophy was assessed with voxel-based morphometry comparing the two groups with 148 healthy controls on MRI. Connectivity data were evaluated with resting-state MRI of 12 large-scale brain networks in 84 people in the asymptomatic group, 70 people in the simultaneous group, and 90 controls. The researchers reported results with P <0.05.
In the simultaneous group, gray matter atrophy was seen in the left cingulum (86 voxels) and the inferior frontal lobe (91 voxels). The asymptomatic group had no gray atrophy.
The simultaneous group presented a widespread, bilateral pattern of hyperconnectivity involving all 12 networks; the asymptomatic group showed hyperconnectivity involving only five networks.
"This abstract, along with all the other evidence, is a compelling reason to double our effort to further understand long COVID and its various sequelae or consequences," Al-Aly said.
"Understanding the long-term health effects of SARS-CoV-2 infection will not only help us understand long COVID, but more broadly will deepen our understanding of infection-associated chronic illnesses -- an entity that has been ignored for more than 100 years," he added. "It will also help prepare us better for the next pandemic."