Gray Matter Thickness and Subcortical Nuclear Volume in Men After SARS-CoV-2 Omicron Infection

The clinical manifestations and effects on the brain of the SARS-CoV-2 Omicron variant in the acute postinfection phase remain unclear.

To investigate the pathophysiological mechanisms underlying clinical symptoms and changes to gray matter and subcortical nuclei among male patients after Omicron infection and to provide an imaging basis for early detection and intervention.

In this cohort study, a total of 207 men underwent health screening magnetic resonance imaging scans between August 28 and September 18, 2022; among them, 98 provided complete imaging and neuropsychiatric data. Sixty-one participants with Omicron infection were reevaluated after infection (January 6 to 14, 2023). Neuropsychiatric data, clinical symptoms, and magnetic resonance imaging data were collected in the acute post-Omicron period, and their clinical symptoms were followed up after 3 months. Gray matter indexes and subcortical nuclear volumes were analyzed. Associations between changes in gray matter and neuropsychiatric data were evaluated with correlation analyses.

Gray matter thickness and subcortical nuclear volume change data were compared before and after Omicron infection.

The gray matter indexes and subcutaneous nuclear volume were generated from the 3-dimensional magnetization-prepared rapid acquisition gradient echo and were calculated with imaging software.

Ninety-eight men underwent complete baseline data collection; of these, 61 (mean [SD] age, 43.1 [9.9] years) voluntarily enrolled in post-Omicron follow-up and 17 (mean [SD] age, 43.5 [10.0] years) voluntarily enrolled in 3-month follow-up. Compared with pre-Omicron measures, Beck Anxiety Inventory scores were significantly increased (median, 4.50 [IQR, 1.00-7.00] to 4.00 [IQR, 2.00-9.75]; P = .006) and depressive distress scores were significantly decreased (median, 18.00 [IQR, 16.00-20.22] to 16.00 [IQR, 15.00-19.00]; P = .003) at the acute post-Omicron follow-up. Fever, headache, fatigue, myalgia, cough, and dyspnea were the main symptoms during the post-Omicron follow-up; among the participants in the 3-month follow-up, fever (11 [64.7%] vs 2 [11.8%]; P = .01), myalgia (10 [58.8%] vs 3 (17.6%]; P = .04), and cough (12 [70.6%] vs 4 [23.5%]; P = .02) were significantly improved. The gray matter thickness in the left precuneus (mean [SD], 2.7 [0.3] to 2.6 [0.2] mm; P < .001) and right lateral occipital region (mean [SD], 2.8 [0.2] to 2.7 [0.2] and 2.5 [0.2] to 2.5 [0.2] mm; P < .001 for both) and the ratio of the right hippocampus volume to the total intracranial volume (mean [SD]. 0.003 [0.0003] to 0.003 [0.0002]; P = .04) were significantly reduced in the post-Omicron follow-up. The febrile group had reduced sulcus depth of the right inferior parietal region compared with the nonfebrile group (mean [SD], 3.9 [2.3] to 4.8 [1.1]; P = .048. In the post-Omicron period, the thickness of the left precuneus was negatively correlated with the Beck Anxiety Inventory scores (r = -0.39; P = .002; false discovery rate P = .02), and the ratio of the right hippocampus to the total intracranial volume was positively correlated with the Word Fluency Test scores (r = 0.34; P = .007).

In this cohort study of male patients infected with the Omicron variant, the duration of symptoms in multiple systems after infection was short. Changes in gray matter thickness and subcortical nuclear volume injury were observed in the post-Omicron period. These findings provide new insights into the emotional and cognitive mechanisms of an Omicron infection, demonstrate its association with alterations to the nervous system, and verify an imaging basis for early detection and intervention of neurological sequelae.