Trender William, Hellyer Peter J, Killingley Ben, Kalinova Mariya, Mann Alex J, Catchpole Andrew P, Menon David, Needham Edward, Thwaites Ryan, Chiu Christopher, Scott Gregory, Hampshire Adam
Department of Brain Sciences, Imperial College London, UK.
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
EClinicalMedicine. 2024 Sep 21;76:102842. doi: 10.1016/j.eclinm.2024.102842. eCollection 2024 Oct.
Patient-reported outcomes and cross-sectional evidence show an association between COVID-19 and persistent cognitive problems. The causal basis, longevity and domain specificity of this association is unclear due to population variability in baseline cognitive abilities, vulnerabilities, virus variants, vaccination status and treatment.
Thirty-four young, healthy, seronegative volunteers were inoculated with Wildtype SARS-CoV-2 under prospectively controlled conditions. Volunteers completed daily physiological measurements and computerised cognitive tasks during quarantine and follow-up at 30, 90, 180, 270, and 360 days. Linear modelling examined differences between 'infected' and 'inoculated but uninfected' individuals. The main cognitive endpoint was the baseline corrected global cognitive composite score across the battery of tasks administered to the volunteers. Exploratory cognitive endpoints included baseline corrected scores from individual tasks. The study was registered on ClinicalTrials.gov with the identifier NCT04865237 and took place between March 2021 and July 2022.
Eighteen volunteers developed infection by qPCR criteria of sustained viral load, one without symptoms and the remainder with mild illness. Infected volunteers showed statistically lower baseline-corrected global composite cognitive scores than uninfected volunteers, both acutely and during follow up (mean difference over all time points = -0.8631, 95% CI = -1.3613, -0.3766) with significant main effect of group in repeated measures ANOVA (F (1,34) = 7.58, p = 0.009). Sensitivity analysis replicated this cross-group difference after controlling for community upper respiratory tract infection, task-learning, remdesivir treatment, baseline reference and model structure. Memory and executive function tasks showed the largest between-group differences. No volunteers reported persistent subjective cognitive symptoms.
These results support larger cross sectional findings indicating that mild Wildtype SARS-CoV-2 infection can be followed by small changes in cognition and memory that persist for at least a year. The mechanistic basis and clinical implications of these small changes remain unclear.
This study was funded through the UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy (BEIS) of Her Majesty's Government. WT was funded by the EPSRC through the CDT for Neurotechnology Imperial College London.
患者报告的结果和横断面证据表明，2019冠状病毒病（COVID-19）与持续性认知问题之间存在关联。由于基线认知能力、脆弱性、病毒变体、疫苗接种状况和治疗方面的人群差异，这种关联的因果基础、持续时间和领域特异性尚不清楚。
34名年轻、健康、血清学阴性的志愿者在预先控制的条件下接种野生型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。志愿者在隔离期间以及30天、90天、180天、270天和360天的随访期间完成每日生理测量和计算机化认知任务。线性模型分析了“感染”个体和“接种但未感染”个体之间的差异。主要认知终点是对志愿者进行的一系列任务的基线校正后的总体认知综合评分。探索性认知终点包括各个任务的基线校正分数。该研究已在ClinicalTrials.gov上注册，标识符为NCT04865237，研究于2021年3月至2022年7月进行。
根据qPCR持续病毒载量标准，18名志愿者发生感染，1名无症状，其余有轻症。感染的志愿者在急性期和随访期间的基线校正后的总体综合认知评分在统计学上低于未感染的志愿者（所有时间点的平均差异=-0.8631，95%置信区间=-1.3613，-0.3766），重复测量方差分析中组的主效应显著（F(1,34)=7.58，p=0.009）。敏感性分析在控制社区上呼吸道感染、任务学习、瑞德西韦治疗、基线参考和模型结构后重现了这种组间差异。记忆和执行功能任务显示出最大的组间差异。没有志愿者报告持续性主观认知症状。
这些结果支持了更大规模的横断面研究结果，表明轻度野生型SARS-CoV-2感染后可能会出现持续至少一年的认知和记忆小变化。这些小变化的机制基础和临床意义仍不清楚。
本研究由英国女王陛下政府商业、能源和产业战略部（BEIS）的英国疫苗特遣部队资助。WT由工程和物理科学研究委员会（EPSRC）通过伦敦帝国理工学院神经技术博士培训中心资助。
