Association between Alzheimer's disease and COVID 19: A bidirectional Mendelian randomization

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Not applicable. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data generated or analyzed during this study are included in this published article and its supplementary information files.