van Lith Theresa J, Li Hao, van der Wijk Marte W, Wijers Naomi T, Sluis Wouter M, Wermer Marieke J H, de Leeuw Frank-Erik, Meijer Frederick J A, Tuladhar Anil M
Department of Neurology, Donders Center for Medical Neurosciences, Radboud University Medical Center, Nijmegen, Netherlands.
Department of Neurology, Leiden University Medical CenterLeiden, Netherlands.
Front Neurol. 2024 Aug 8;15:1440294. doi: 10.3389/fneur.2024.1440294. eCollection 2024.
SARS-CoV-2 infection is associated with a decline in functional outcomes; many patients experience persistent symptoms, while the underlying pathophysiology remains unclear. This study investigated white matter (WM) integrity on brain MRI in hospitalized COVID-19 patients and its associations with clinical outcomes, including long COVID.
We included hospitalized COVID-19 patients and controls from CORONavirus and Ischemic Stroke (CORONIS), an observational cohort study, who underwent MRI-DWI imaging at baseline shortly after discharge (<3 months after positive PCR) and 3 months after baseline scanning. We assessed WM integrity using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) and performed comparisons between groups and within patients. Clinical assessment was conducted at 3 and 12 months with functional outcomes such as modified Rankin Scale (mRS), Post-COVID-19 Functional Status scale (PCFS), Visual Analogue Scale (VAS), and long COVID, cognitive assessment was conducted by the Modified Telephone Interview for Cognitive Status (TICS-M), and the Hospital Anxiety and Depression Scale (HADS) was used to assess mood disorder. Associations between WM integrity and clinical outcomes were evaluated using logistic regression and linear regression.
A total of 49 patients (mean age 59.5 years) showed higher overall peak width of skeletonized mean diffusivity (PSMD) ( = 0.030) and lower neurite density index (NDI) in several WM regions compared with 25 controls at the baseline ( < 0.05; FWE-corrected) but did not remain statistically significant after adjusting for WM hyperintensities. Orientation dispersion index (ODI) increased after 3-month follow-up in several WM regions within patients ( < 0.05), which remained significant after correction for changes in WMH volume. Patients exhibited worse clinical outcomes compared with controls. Low NDI at baseline was associated with worse performance on the Post-COVID-19 Functional Status scale after 12 months ( = 0.018).
After adjusting for WMH, hospitalized COVID-19 patients no longer exhibited lower WM integrity compared with controls. WM integrity was generally not associated with clinical assessments as measured shortly after discharge, suggesting that factors other than underlying WM integrity play a role in worse clinical outcomes or long COVID.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染与功能预后下降有关；许多患者会出现持续症状，但其潜在的病理生理学仍不清楚。本研究调查了住院的2019冠状病毒病（COVID-19）患者脑磁共振成像（MRI）上的白质（WM）完整性及其与临床结局的关联，包括新冠后综合征。
我们纳入了来自冠状病毒与缺血性卒中（CORONIS）观察性队列研究中的住院COVID-19患者及对照组，这些患者在出院后不久（PCR检测呈阳性后<3个月）的基线期以及基线扫描后3个月接受了磁共振扩散加权成像（MRI-DWI）检查。我们使用扩散张量成像（DTI）和神经突方向离散度与密度成像（NODDI）评估WM完整性，并在组间和患者内部进行比较。在3个月和12个月时进行临床评估，评估指标包括改良Rankin量表（mRS）、COVID-19后功能状态量表（PCFS）、视觉模拟量表（VAS）以及新冠后综合征；通过改良认知状态电话访谈（TICS-M）进行认知评估，并使用医院焦虑抑郁量表（HADS）评估情绪障碍。使用逻辑回归和线性回归评估WM完整性与临床结局之间的关联。
与25名对照组相比，共有49名患者（平均年龄59.5岁）在基线期时多个WM区域的整体骨架化平均扩散率峰值宽度（PSMD）更高（=0.030），神经突密度指数（NDI）更低（<0.05；FWE校正），但在调整WM高信号后不再具有统计学意义。患者在3个月随访后多个WM区域的方向离散度指数（ODI）增加（<0.05），在校正WMH体积变化后仍具有显著性。与对照组相比，患者的临床结局更差。基线期低NDI与12个月后COVID-19后功能状态量表表现更差相关（=0.018）。
在调整WMH后，住院COVID-19患者与对照组相比不再表现出更低的WM完整性。出院后不久进行测量时，WM完整性通常与临床评估无关，这表明除了潜在的WM完整性外，其他因素在更差的临床结局或新冠后综合征中起作用。
