Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
Department of Pharmacology and Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Front Public Health. 2023 Aug 22;11:1185957. doi: 10.3389/fpubh.2023.1185957. eCollection 2023.
A substantial proportion of individuals with COVID-19 experienced cognitive impairment after resolution of SARS-CoV-2 infection. We aimed to evaluate whether genetic liability to SARS-CoV-2 infection , or more severe COVID-19, is causally linked to cognitive deficit.
We firstly performed univariable Mendelian randomization (MR) analysis to examine whether genetic liability to SARS-CoV-2 infection, hospitalized and severe COVID-19 is causally associated with cognitive performance. To dissect the causal pathway, multivariable MR (MVMR) analysis was conducted by adjusting for five inflammatory markers [C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor α, as proxies of systemic inflammation].
In univariable MR analysis, host genetic liability to SARS-CoV-2 infection was associated with lower cognitive performance [inverse variance weighted (IVW) analysis, estimate: -0.023; 95% Confidence Interval (CI): -0.038 to -0.009]. Such causal association was attenuated in MVMR analysis when we adjusted for the five correlated inflammatory markers in one analysis (IVW analysis, estimate: -0.022; 95% CI: -0.049 to 0.004). There was insufficient evidence of association for genetic liability to hospitalized and severe COVID-19 with cognitive performance.
The causal effect of host genetic liability to SARS-CoV-2 infection on reduced cognitive performance may be mediated by systemic inflammation. Future studies examining whether anti-inflammatory agents could alleviate cognitive impairment in SARS-CoV-2-infected individuals are warranted.
相当一部分 COVID-19 患者在 SARS-CoV-2 感染痊愈后出现认知障碍。我们旨在评估 SARS-CoV-2 感染的遗传易感性，或更严重的 COVID-19 是否与认知缺陷有因果关系。
我们首先进行单变量孟德尔随机化（MR）分析，以评估 SARS-CoV-2 感染、住院和严重 COVID-19 的遗传易感性是否与认知表现有因果关系。为了剖析因果途径，我们通过调整五个炎症标志物[C 反应蛋白、白细胞介素（IL）-1β、IL-6、IL-8 和肿瘤坏死因子 α，作为全身炎症的替代指标]进行多变量 MR（MVMR）分析。
在单变量 MR 分析中，宿主对 SARS-CoV-2 感染的遗传易感性与较低的认知表现相关[逆方差加权（IVW）分析，估计值：-0.023；95%置信区间（CI）：-0.038 至 -0.009]。当我们在一次分析中调整五个相关炎症标志物时，这种因果关系在 MVMR 分析中减弱（IVW 分析，估计值：-0.022；95% CI：-0.049 至 0.004）。对于住院和严重 COVID-19 的遗传易感性与认知表现之间的关联，证据不足。
宿主对 SARS-CoV-2 感染的遗传易感性对认知表现下降的因果效应可能通过全身炎症介导。未来研究应检查抗炎症药物是否能减轻 SARS-CoV-2 感染个体的认知障碍。
