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. 2023 Jan:319:114969.
doi: 10.1016/j.psychres.2022.114969. Epub 2022 Nov 24.

Two-year follow-up of brain structural changes in patients who recovered from COVID-19: A prospective study

Yanyao Du  1 , Wei Zhao  2 , Sihong Huang  1 , Yijie Huang  1 , Yanjing Chen  1 , Huiting Zhang  3 , Hu Guo  4 , Jun Liu  5
Affiliations

Two-year follow-up of brain structural changes in patients who recovered from COVID-19: A prospective study

Yanyao Du et al. Psychiatry Res. 2023 Jan.

Abstract

The long-term effects of COVID-19 on brain structure remain unclear. A prospective study was conducted to explore the changes in brain structure in COVID-19 survivors at one and two years after discharge (COVID-19one, COVID-19two). The difference in gray matter volume (GMV) was analyzed using the voxel-based morphometry method, and correlation analyses were conducted. The dynamic changes in clinical sequelae varied. The GMVs in the cerebellum and vermis were reduced in COVID-19one and COVID-19two, positively correlated with lymphocyte count, and negatively correlated with neutrophil count, neutrophil/lymphocyte ratio (COVID-19one), and systemic immune-inflammation index (COVID-19two). The decreased GMVs in the left middle frontal gyrus, inferior frontal gyrus of the operculum, right middle temporal gyrus, and inferior temporal gyrus returned to normal in COVID-19two. The decreased GMV in the left frontal lobe was negatively correlated with the Athens Insomnia Scale (AIS). The GMV in the left temporal lobe was aggravated in COVID-19two and positively correlated with C-reactive protein. In conclusion, GMV recovery coexisted with injury, which was associated with AIS and inflammatory factors. This may shed some light on the dynamic changes in brain structure and the possible predictors that may be related to GMV changes in COVID-19two.

Keywords: COVID-19 clinical sequelae; Cross-sectional study; Gray matter volume changes; Voxel-based morphometry; longitudinal follow-up.

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Conflict of interest statement

Declaration of Competing Interest The authors have no conflict of interest.

Figures

Fig 1
Fig. 1
Flowchart of the study.
Fig 2
Fig. 2
Clinical symptoms in the acute stage, COVID-19one, and COVID-19two.
Fig 3
Fig. 3
Results of VBM analysis and post hoc ROI analysis between COVID-19one and HCs, COVID-19two and HCs, and COVID-19one and COVID-19two. (A) Compared with the HCs, the COVID-19one showed significantly reduced GMV in the bilateral cerebellum and vermis, left MFG and IFGoperc, and right MTG and ITG. (B) Compared with the HCs, the COVID-19two showed significantly reduced GMV in the bilateral cerebellum and vermis, left MTG and fusiform. (C) Significant difference in the left ITG between COVID-19one and COVID-19two. VBM, voxel-based morphometry. ROI, region of interest. R, right. L, left. GMV, gray matter volume. COVID-19one, patients one year post-recovery after SARS-CoV-2 infection. COVID-19two, patients two years post-recovery after SARS-CoV-2 infection. HCs, healthy controls. MFG, middle frontal gyrus. IFGoperc, inferior frontal gyrus of operculum. MTG, middle temporal gyrus. ITG, inferior temporal gyrus.
Fig 4
Fig. 4
Correlation analyses results. (A, B) The GMV in the bilateral cerebellum and vermis was positively correlated with the lymphocyte count, and the GMV in the left MFG and IFGoperc was negatively correlated with AIS in COVID-19one. (C, D, E) In COVID-19two, the GMV in the bilateral cerebellum and vermis was negatively correlated with the neutrophil count (PFDR = 0.040), NLR (PFDR = 0.025), and SII (PFDR = 0.035). (F) The difference in GMV in the left ITG between the two groups was positively correlated with CRP. GMV, gray matter volume. COVID-19one, patients one-year post-recovery after SARS-CoV-2 infection. COVID-19two, patients two years post-recovery after SARS-CoV-2 infection. AIS, Athens Insomnia Scale. MFG, middle frontal gyrus. IFGoperc, inferior frontal gyrus of operculum. MTG, middle temporal gyrus. ITG, inferior temporal gyrus. NLR, neutrophil/lymphocyte ratio. SII, systemic immune-inflammation index. CRP, C-reactive protein.
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