COVID-19 impacts gray matter volume, especially among those with fever, receipt of oxygen

Patients with COVID-19 experienced changes in gray matter volume, especially those with fever and those who received oxygen therapy, according to findings from a multivariate, observational study published in Neurobiology of Stress.

The results indicate that COVID-19 may impact the frontal-temporal network of the brain “in a secondary manner through fever or lack of oxygen,” the researchers wrote.

“Neuroimaging data provide us a good opportunity to study links between COVID-19 and the central nervous system,” Kuaikuai Duan, a PhD student and graduate research assistant at the Translational Research in Neuroimaging and Data Sciences and Georgia Institute of Technology, and colleagues wrote. “However, to date, only a few studies have examined the effect of COVID-19 on the brain, and previous findings are inconsistent.”

Duan and colleagues used source-based morphometry analysis, a multivariate extension of voxel-based morphometry analysis, to examine changes identified on CT scans in covarying gray matter volume among 120 neurological patients. This included 58 patients with COVID-19 and 62 patients without COVID-19 who were matched for age, sex and diseases, according to the study findings.

Patients with COVID-19 were older than patients without COVID-19 (mean age, 73.41 years vs. 69.46 years). The distribution of men and women in each group was similar.

Neurological complications and confounding variables reported by the researchers included agitation (n = 25 in patients with COVID-19 vs. n = 10 in patients without COVID-19), cerebrovascular events (n = 39 in patients with COVID-19 vs. n = 36 in patients without COVID-19), diabetes (n = 15 in patients with COVID-19 vs. n = 7 in patients without COVID-19) and hypertension (n = 30 in patients with COVID-19 vs. n = 41 in patients without COVID-19).

The source-based morphometry analysis demonstrated that decreased gray matter volume in the superior, medial and middle frontal gyri correlated significantly with a greater level of disability according to the modified Rankin scale at both discharge and the 6-month follow-up phase. This association persisted even after the researchers controlled for cerebrovascular diseases, according to the study findings.

Specifically, Duan and colleagues found that gray matter volume in the superior, medial and middle frontal gyri was significantly reduced among patients receiving oxygen therapy compared with patients who did not receive such treatment. Additionally, patients with fever experienced significant decreases in gray matter volume in the inferior and middle temporal gyri and fusiform gyrus compared with patients without fever. Patients with agitation demonstrated decreases in gray matter volume in the superior, medial and middle frontal gyri compared to patients without agitation.

“The result that patients who received oxygen therapy presented reduced [gray matter volume] in frontal regions can be supported by the observations that individuals who were lack of oxygen supply to the brain demonstrated regional [gray matter volume] reduction,” Duan and colleagues wrote. “Patients with chronic obstructive pulmonary disease that can cause reduced oxygen supply to the brain have shown [gray matter volume] reduction in widespread regions, including the frontal cortex, the cingulate cortex and other subcortical regions.”

The impact of COVID-19 on the brain’s structure, function, metabolism and activity in the frontal and temporal lobes “are increasingly reported as being affected by COVID-19,” according to the researchers.

“This study leveraged a multivariate blind source separation method, [source-based morphometry], to identify CT-derived [gray matter volume] alterations underlying COVID-19 in 120 older adults,” Duan and colleagues wrote. “Importantly, [gray matter volume] alterations in the identified frontal-temporal network can predict individual disability levels [ie, modified Rankin scale] at both discharge and 6 months follow-up for the hold-out testing samples, implying that the frontal-temporal network can be potentially employed as a biomarker for prognosis and evaluation of treatment of COVID-19.”