兒童長新冠症候群之神經心理、視知覺與腦影像的長期影響

Abstract

研究背景：長新冠症候群（long COVID syndrome）為新冠病毒（COVID-19）感染之急性期過後，患者仍持續表現多樣、波動的症狀，進而對日常生活造成長期的影響。 迄今為止，有大量的研究調查了新冠病毒對成人的長期影響，但對於兒童與青少年族群的相關研究仍相當缺乏。因此，本研究旨在探討兒童長新冠症候群之神經心理症狀與視知覺表現，並進一步比較兒童及青少年在新冠感染後，不同神經心理症狀嚴重度之長期大腦結構差異與其相關性。

研究方法：我們招募了 65 名年齡介於6至18歲，經PCR或快篩呈現新冠感染陽性且距離確診5至8個月的受試者參與研究。考量長新冠神經心理症狀的多樣性，我們根據症狀的嚴重程度及其與大腦之相關性，為每種症狀訂定 0-3 之間不同的加權分數。受試者在家長協助下完成急性期和慢性期神經心理症狀的回顧性問卷，並依填答症狀之加權分數區分為嚴重與輕微症狀兩組，以利後續分析。此外，所有受試者皆完成視知覺技能測驗-第四版（TVPS-4）以評估視知覺能力，並透過3.0 Tesla SIEMENS MAGNETOM Prisma儀器進行核磁共振造影（MRI） 掃描以獲取腦部結構資料。關於腦部結構分析，我們利用 FreeSurfer 軟體來做影像前處理與皮質分區以獲取各皮質與皮質下區域之灰質體積資料來進行後續統計。

研究結果：結果顯示，兒童與青少年長新冠最常見的神經心理症狀是頭痛、頭暈、注意力不集中以及記憶力減退，這些症狀可持續長達 6 個月。在嚴重神經心理症狀的組別中，部分皮質下和顳葉區的灰質體積顯著增大，而這些腦區差異與急慢性神經心理症狀皆有顯著正相關，顯示神經心理症狀越嚴重、有越大程度的大腦皮質結構差異。此外，TVPS-4 測驗結果顯示，具有視覺相關症狀的組別，比起健康對照組，總體標準分數和順序記憶子測驗分數顯著較低。

研究結論：儘管感染新冠病毒的兒童和青少年很少會引起危重病情且大多數預後良好，但在兒童與青少年長新冠患者中仍可觀察到長期的神經心理症狀、較差的視知覺表現和腦部灰質結構的差異，此客觀證據顯示長新冠對於這個年齡層的影響仍不容忽視。此外，我們也發現急性期神經心理症狀的嚴重程度可以作為慢性期神經心理症狀嚴重程度和大腦結構差異的預測因子。未來需要更大樣本量與縱向追蹤的研究來驗證這些發現，以提供兒童長新冠預防與治療的方向。

Background: Long COVID exhibits variable persistent symptoms and durations following COVID-19 infection and causes impact on daily life. To date, there have been numerous studies investigating long-term influence of COVID-19 in adults, but the data in children and adolescents remains scarce. Thus, this study attempts to explore the neuropsychiatric symptoms and compare brain volume differences and visual perception function between children and adolescents with severe and mild or no subjective neuropsychiatric symptoms during 5 to 8 months after COVID-19 infection.

Methods: Total 65 participants aged from 6 to 18 years old and tested positive for COVID-19 antibody were recruited at 5 to 8 months after the infection. Due to the diversity of the symptoms, we assigned different weighted scores from 0-3 to each symptom regarding their severity and relationship to the brain. Participants completed retrospective questionnaires on neuropsychiatric symptoms in acute and chronic phases, and were then divided into two groups based on their symptom severity. All participants underwent MRI scans, that were performed on a 3.0 Tesla SIEMENS MAGNETOM Prisma scanner. For the brain volume analysis, we utilized FreeSurfer's protocols to acquire parcels generated. The Test of Visual Perceptual Skills—fourth edition (TVPS-4) was utilized to assess visual perception for all the participants.

Results: The results showed that the most common neuropsychiatric symptoms are headache or dizziness, and attention and memory deficit, which persist for up to 6 months. Gray matter volumes significantly enlarged in group with severe symptoms in subcortical and temporal areas, and these brain volume differences significantly correlated to the acute and chronic symptoms. When examining the scores of TVPS-4, significant differences were observed in overall standard scores and Sequential Memory subtests between those with visual-related symptoms and healthy controls.

Conclusions: Although children and adolescents who were infected with COVID-19 rarely cause critical conditions and mostly have a good prognosis, several neuropsychiatric symptoms, poor visual perception performance, and gray matter volumes differences were present in pediatric long-COVID syndrome. We also found that the severity of neuropsychiatric symptoms during the acute phase may serve as a predictive factor for the severity and brain volume differences of chronic phase. Longitudinal follow-up studies with larger sample size are essential to validate these findings.