Background In observational studies, Alzheimer's disease (AD) has been associated with an increased risk of Coronavirus disease 2019 (COVID-19), and the prognosis of COVID-19 can affect nervous systems. However, the causality between these conditions remains to be determined. Methods This study sought to investigate the bidirectional causal relations of AD with COVID-19 using two-sample Mendelian randomization (MR) analysis. Results We found that genetically predicted AD was significantly associated with higher risk of severe COVID-19 (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.139-9.725; P=0.028). It's interesting that genetically predicted severe COVID-19 was also significantly associated with higher risk of AD (OR, 1.004; 95% CI, 1.001-1.007; P=0.018). In addition, the two strong genetic variants associated with severe COVID-19 was associated with higher AD risk (OR, 1.018; 95% CI, 1.003-1.034; P=0.018). There is no evidence to support that genetically predicted AD was significantly associated with COVID-19 susceptibility, and vice versa. No obvious pleiotropy bias and heterogeneity were observed. Conclusion Overall, AD may causally affect severe COVID-19, and vice versa, performing bidirectional regulation through independent biological pathways.

中文翻译：

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阿尔茨海默氏病与COVID-19之间的关联：孟德尔双向双向

背景在观察性研究中，阿尔茨海默氏病（AD）与2019年冠状病毒病（COVID-19）的风险增加相关，并且COVID-19的预后可能会影响神经系统。但是，这些条件之间的因果关系仍有待确定。方法本研究试图通过两次样本孟德尔随机（MR）分析研究AD与COVID-19的双向因果关系。结果我们发现，遗传预测的AD与严重COVID-19的较高风险显着相关（比值比[OR]为3.329； 95％置信区间[CI]为1.139-9.725； P = 0.028）。有趣的是，遗传预测的严重COVID-19也与较高的AD风险显着相关（OR为1.004； 95％CI为1.001-1.007； P = 0.018）。此外，与严重COVID-19相关的两个强遗传变异与较高的AD风险相关（OR，1.018； 95％CI，1.003-1.034； P = 0.018）。没有证据支持遗传预测的AD与COVID-19易感性显着相关，反之亦然。没有观察到明显的多效性偏倚和异质性。结论总体而言，AD可能会通过严重的COVID-19引起因果关系，反之亦然，并通过独立的生物学途径进行双向调节。