Impact of COVID-19 on the Pediatric Brain: A Structural MRI Study

2298 

Abstract Submission 

Ting Peng¹, Yujie Chen², Zhuoyang Gu², Weijia Zhang², Han Zhang², Chaowei Zhang³, Xianghui Huang³, Guoqiang Cheng³, Jungang Liu⁴

¹Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China, ²School of Biomedical Engineering, ShanghaiTech University, Shanghai, China, ³Fujian Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University (Xiamen Branch), Xiamen, China, ⁴Department of Radiology, Xiamen Children's Hospital, Children's Hospital of Fudan University at Xiam, Xiamen, China

Ting Peng  
Department of Neonatology, Children's Hospital of Fudan University
Shanghai, China

Yujie Chen  
School of Biomedical Engineering, ShanghaiTech University
Shanghai, China

Zhuoyang Gu  
School of Biomedical Engineering, ShanghaiTech University
Shanghai, China

Weijia Zhang  
School of Biomedical Engineering, ShanghaiTech University
Shanghai, China

Han Zhang  
School of Biomedical Engineering, ShanghaiTech University
Shanghai, China

Chaowei Zhang  
Fujian Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University (Xiamen Branch)
Xiamen, China

Xianghui Huang  
Fujian Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University (Xiamen Branch)
Xiamen, China

Guoqiang Cheng  
Fujian Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University (Xiamen Branch)
Xiamen, China

Jungang Liu  
Department of Radiology, Xiamen Children's Hospital, Children's Hospital of Fudan University at Xiam
Xiamen, China

The COVID-19 pandemic has caused unprecedented physical and mental problems to infected individuals. Mounting evidence indicates that SARS-CoV-2 negatively influences human CNS including the brain (Shen et al. 2022), suggesting neurological deficits caused by the virus. Given that the first several years of life represents a critical stage in human brain development, we hypothesized that COVID-19 infection may cause more significant changes in the brain structure in young children than adults (Gilmore et al. 2018). While numerous studies have been conducted on the impact of COVID-19 on human brain, little is known regarding its impact on the pediatric populations. To resolve this issue, we recruited a group of children with COVID-19 and compared their structure with age- and gender-matched healthy control children based on high-resolution structural MRI. The whole-brain vertex-wise morphometric analysis, as well as structural covariance network construction and analysis, were performed to explore COVID-19 impact on the children's brain.

We enrolled 17 children (age 3.2 ± 1.8 years) diagnosed with mild COVID-19 and 19 age-/sex-matched (P>0.05) healthy children (age 3.7 ± 1.5 years). Their 3D high-resolution T1w structural MRI data with 0.8mm isotropic voxels were obtained by a 3.0T scanner (uMR890, United Imaging) and preprocessed using FreeSurfer (Fischl et al. 2000). Various cortical metrics (cortical thickness, area, volume, and local gyrification index (LGI)) were compared between the two groups with vertex-wise general linear models (vertex-wise P<0.01, cluster-wise P<0.05) after controlling age, gender, and total intracranial volume (eTIV). We further extracted cortical LGI histogram for each of the 68 brain regions defined by the Desikan-Killiany Atlas and constructed structural covariance networks using Graph Analysis Toolbox (Hosseini et al. 2012). The edges were defined as Pearson correlation coefficients between LGI histograms of each pair of the brain regions adjusted for age, gender, and eTIV. The structural covariance networks were then binarized according to density thresholds ranging from 0.24 to 0.38 (with an increment of 0.01) according to the literature documented elsewhere (Humphries et al. 2006). Global (clustering coefficient, path length, and small-world index) and regional metrics (nodal betweenness centrality, nodal degree, and local efficiency) were calculated (Rubinov et al. 2010) and the area under the curve (AUC) of the network parameters across all densities was compared using non-parametric permutation tests (P<0.05, false discovery rate [FDR] corrected).

The vertex-wise comparison results on cortical measurements were summarized in Table 1. Compared to the control group, patients with COVID-19 showed a significant increase in cortical area, volume, and LGI at the left superior parietal cortex, and in cortical thickness at the left lateral occipital cortex. Further exploration of the between-group differences indicated that brain cortical LGI network changed its topology towards less optimized clustering coefficient in the COVID-19 group (P<0.05, Figure 1), whereas other network global indices did not show statistical significance. Finally, we found no significant difference in the regional network measures after FDR correction.

Our study provided the first report of reduced clustering coefficient in brain cortical geometric networks in young children with COVID-19, despite of no difference in regional networks parameters. We speculate that virus-triggered neuroinflammation and immune response may cause neurotoxic consequences in children's brain, leading to cortical geometric changes and global network changes and further impairing cognitive abilities during such a pivotal development period (so-called "long-COVID").

Neurodevelopmental/ Early Life (eg. ADHD, autism) ²

Early life, Adolescence, Aging

Other Methods

Anatomical MRI ¹

Cognition

Cortex

Data analysis

Development

Infections

MRI

Pediatric Disorders

STRUCTURAL MRI

Other - COVID