Widmann Catherine N, Wieberneit Michelle, Bieler Luzie, Bernsen Sarah, Gräfenkämper Robin, Brosseron Frederic, Schmeel Carsten, Tacik Pawel, Skowasch Dirk, Radbruch Alexander, Heneka Michael T
Section Neuropsychology, Department of Neurodegenerative Diseases and Gerontopsychiatry, University of Bonn Medical Center, Bonn, Germany.
German Center for Neurodegenerative Diseases, Bonn, Germany.
JMIR Res Protoc. 2021 Nov 11;10(11):e30259. doi: 10.2196/30259.
There is a dearth of information about "brain fog," characterized by concentration, word-finding, or memory problems, which has been listed in the new World Health Organization provisional classification "U09.9 Post-COVID-19 Condition." Moreover, the extent to which these symptoms may be associated with neurological, pulmonary, or psychiatric difficulties is unclear.
This ongoing cohort study aims to carefully assess neurocognitive function in the context of the neurological, psychiatric, and pulmonary sequelae of SARS-CoV-2 infection among patients with asymptomatic/mild and severe cases of COVID-19 after remission, including actively recruited healthy controls.
A total of 150 participants will be included in this pilot study. The cohort will comprise patients who tested positive for SARS-CoV-2 infection with either an asymptomatic course or a mild course defined as no symptoms except for olfactory and taste dysfunction (n=50), patients who tested positive for SARS-CoV-2 infection with a severe disease course (n=50), and a healthy control group (n=50) with similar age and sex distribution based on frequency matching. A comprehensive neuropsychological assessment will be performed comprising nuanced aspects of complex attention, including language, executive function, verbal and visual learning, and memory. Psychiatric, personality, social and lifestyle factors, sleep, and fatigue will be evaluated. Brain magnetic resonance imaging, neurological and physical assessment, and pulmonological and lung function examinations (including body plethysmography, diffusion capacity, clinical assessments, and questionnaires) will also be performed. Three visits are planned with comprehensive testing at the baseline and 12-month visits, along with brief neurological and neuropsychological examinations at the 6-month assessment. Blood-based biomarkers of neurodegeneration will be quantified at baseline and 12-month follow-up.
At the time of submission, the study had begun recruitment through telephone and in-person screenings. The first patient was enrolled in the study at the beginning of April 2021. Interim data analysis of baseline information is expected to be complete by December 2021 and study completion is expected at the end of December 2022. Preliminary group comparisons indicate worse word list learning, short- and long-delayed verbal recall, and verbal recognition in both patient cohorts compared with those of the healthy control group, adjusted for age and sex. Initial volumetric comparisons show smaller grey matter, frontal, and temporal brain volumes in both patient groups compared with those of healthy controls. These results are quite robust but are neither final nor placed in the needed context intended at study completion.
To the best of our knowledge, this is the first study to include objective and comprehensive longitudinal analyses of neurocognitive sequelae of COVID-19 in an extreme group comparison stratified by disease severity with healthy controls actively recruited during the pandemic. Results from this study will contribute to the nascent literature on the prolonged effects of COVID-19 on neurocognitive performance via our coassessment of neuroradiological, neurological, pulmonary, psychiatric, and lifestyle factors.
International Clinical Trials Registry Platform DRKS00023806; https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00023806.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30259.
关于“脑雾”（其特征为注意力不集中、找词困难或记忆问题）的信息匮乏，“脑雾”已被列入世界卫生组织新的临时分类“U09.9 新冠后状况”。此外，这些症状与神经、肺部或精神方面困难的关联程度尚不清楚。
这项正在进行的队列研究旨在仔细评估新冠病毒感染无症状/轻症和重症患者康复后，在新冠病毒感染的神经、精神和肺部后遗症背景下的神经认知功能，包括积极招募的健康对照。
本试点研究共纳入 150 名参与者。队列将包括新冠病毒感染检测呈阳性且病程无症状或为轻症（定义为除嗅觉和味觉功能障碍外无其他症状，n = 50）的患者、新冠病毒感染检测呈阳性且病程为重症（n = 50）的患者，以及基于频率匹配的年龄和性别分布相似的健康对照组（n = 50）。将进行全面的神经心理学评估，包括复杂注意力的细微方面，如语言、执行功能、言语和视觉学习及记忆。将评估精神、人格、社会和生活方式因素、睡眠及疲劳情况。还将进行脑磁共振成像、神经和身体评估以及肺科和肺功能检查（包括体容积描记法、弥散能力、临床评估及问卷）。计划进行三次访视，在基线和 12 个月访视时进行全面检测，在 6 个月评估时进行简短的神经和神经心理学检查。将在基线和 12 个月随访时对基于血液的神经退行性变生物标志物进行定量分析。
在提交本文时，该研究已通过电话和现场筛查开始招募。第一名患者于 2021 年 4 月初入组该研究。预计 2021 年 12 月完成基线信息的中期数据分析，预计 2022 年 12 月底完成研究。初步组间比较表明，在对年龄和性别进行调整后，两个患者队列在单词表学习、短期和长期言语回忆以及言语识别方面均比健康对照组差。初始容积比较显示，与健康对照组相比，两个患者组的灰质、额叶和颞叶脑体积较小。这些结果相当可靠，但既非最终结果，也未置于研究完成时所需的背景中。
据我们所知，这是第一项在疫情期间通过积极招募健康对照，按疾病严重程度进行极端组比较，对新冠病毒感染的神经认知后遗症进行客观且全面纵向分析的研究。通过我们对神经放射学、神经学、肺部、精神和生活方式因素的共同评估，本研究结果将为关于新冠病毒感染对神经认知表现长期影响的新文献做出贡献。
国际临床试验注册平台 DRKS00023806；https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00023806。
国际注册报告识别码（IRRID）：DERR1-10.2196/30259。
