National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA; Evidence-Based Toxicology Collaboration (EBTC), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Evidence-Based Toxicology Collaboration (EBTC), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Neurotoxicology. 2024 Jul;103:16-26. doi: 10.1016/j.neuro.2024.05.003. Epub 2024 May 18.
The global coronavirus 2019 (COVID-19) pandemic began in early 2020, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In mid-2020 the CIAO (Modelling the Pathogenesis of COVID-19 Using the Adverse Outcome Pathway Framework) project was established, bringing together over 75 interdisciplinary scientists worldwide to collaboratively investigate the underlying biological mechanisms of COVID-19 and consolidate the data using the Adverse Outcome Pathway (AOP) Framework. Neurological symptoms such as anosmia and encephalitis have been frequently reported to be associated with infection with SARS-CoV-2.
Within CIAO, a working group was formed to conduct a systematic scoping review of COVID-19 and its related neurological symptoms to determine which key events and modulating factors are most commonly reported and to identify knowledge gaps.
LitCOVID was used to retrieve 86,075 papers of which 10,244 contained relevant keywords. After title and abstract screening, 2,328 remained and their full texts were reviewed based on predefined inclusion and exclusion criteria. 991 studies fulfilled the inclusion criteria and were retrieved to conduct knowledge synthesis.
The majority of publications reported human observational studies. Early key events were less likely to be reported compared to middle and late key events/adverse outcomes. The majority of modulating factors described related to age or sex. Less recognised COVID-19 associated AO or neurological effects of COVID-19 were also identified including multiple sclerosis/demyelination, neurodegeneration/cognitive effects and peripheral neuronal effects.
There were many methodological and reporting issues noted in the reviewed studies. In particular, publication abstracts would benefit from clearer reporting of the methods and endpoints used and the key findings, to ensure relevant papers are included when systematic reviews are conducted. The information extracted from the scoping review may be useful in understanding the mechanisms of neurological effects of COVID-19 and to further develop or support existing AOPs linking COVID-19 and its neurological key events and adverse outcomes. Further evaluation of the less recognised COVID-19 effects is needed.
全球 2019 年冠状病毒病（COVID-19）大流行始于 2020 年初，由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起。2020 年年中，CIAO（使用不良结局途径框架模拟 COVID-19 的发病机制）项目成立，汇集了全球 75 名跨学科科学家，共同合作研究 COVID-19 的潜在生物学机制，并使用不良结局途径（AOP）框架整合数据。嗅觉丧失和脑炎等神经系统症状常与 SARS-CoV-2 感染有关。
在 CIAO 内部，成立了一个工作组，对 COVID-19 及其相关神经系统症状进行系统范围审查，以确定最常报告的关键事件和调节因素，并确定知识空白。
LitCOVID 检索了 86075 篇论文，其中 10244 篇包含相关关键词。在标题和摘要筛选后，仍有 2328 篇论文，根据预先确定的纳入和排除标准对其全文进行了审查。991 项研究符合纳入标准，并进行了知识综合。
大多数出版物报告了人类观察性研究。与中间和晚期关键事件/不良结局相比，早期关键事件不太可能被报告。描述的大多数调节因素与年龄或性别有关。还确定了一些较少认识到的 COVID-19 相关 AOP 或 COVID-19 的神经系统影响，包括多发性硬化症/脱髓鞘、神经退行性变/认知影响和周围神经元影响。
在审查的研究中注意到许多方法学和报告问题。特别是，出版物摘要可以从更清楚地报告使用的方法和终点以及关键发现中受益，以确保在进行系统评价时纳入相关论文。从范围审查中提取的信息可能有助于理解 COVID-19 神经系统影响的机制，并进一步开发或支持将 COVID-19 及其神经系统关键事件和不良结局联系起来的现有 AOP。需要进一步评估较少认识到的 COVID-19 影响。
