COVID‐19 and the risk of Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis

Abstract

Background The coronavirus disease 2019 (COVID‐19) pandemic has had an unprecedented impact on the healthcare system, economy, and society. Studies have reported that COVID‐19 may cause various neurologic symptoms, including cognitive impairment. We aimed to assess the causal effect of COVID‐19 on neurodegenerative diseases using two‐sample Mendelian randomization (MR) study. Methods Genetic variants were obtained from genome‐wide association studies (GWAS) summary‐level data and meta‐analyses. We used the inverse variance–weighted (IVW) method as the primary analysis to estimate causal effects. Sensitivity analyses were performed to make the conclusions more robust and reliable. Results We found that the COVID‐19 infection phenotype was associated with a higher risk of AD and inverse associated with the risk of ALS and MS. The hospitalized COVID‐19 phenotype was associated with the risk of AD and wasn't associated with ALS and MS. We also found that the severe COVID‐19 (main analysis) phenotype was associated with the AD outcome from UK biobank datasets but was not associated with other outcomes. The severe COVID‐19 infection phenotype, the severe COVID‐19 (subtype analysis) phenotype and the hospitalization risk of COVID‐19 were not associated with each outcome. Conclusion This MR study suggests a potential association between genetically predicted COVID‐19 and a higher risk of AD and a reduced risk of ALS and MS. Further elucidations of this association and underlying mechanisms may inform public health messages to prevent COVID‐19 and AD.

A systematic review of Mendelian randomization studies on multiple sclerosis

“…Only COVID hospitalization showed a slight statistically significant causal estimate in increasing MS risk (IVW OR = 1.15 [95% CI: 1.02-1.30], p = .04). On the contrary, previous studies from Zhang and Zhou (2022) and Li, Liu, et al (2022) did not highlight a statistically significant causal effect for COVID hospitalization. Interestingly, in Zhang and Zhou (2022), COVID infection and COVID severity showed a protective statistically significant causal estimate on MS risk, that is, respectively, OR = .79 (95% CI: .70-.88), p < .0001, and OR = .86 (95% CI: .75-.99), p = .03, while these two exposures were not statistically significant in Li, Liu, et al (2022).…”

Probing molecular pathways: Illuminating the connection between COVID‐19 and Alzheimer's disease through the endocannabinoid system dynamics

“…However, they observed a causal relationship between COVID-19 infection and hospitalization in patients when data from the Psychiatric Genomics Consortium was used. 22 Contrarily, UK Biobank data suggested a causal link between AD and various COVID-19 populations, including susceptibility, hospitalization, and severity groups. Sun et al also reported varying findings based on COVID-19 severity 23 (Supporting Information S1: Table 1).…”

COVID-19 delirium and encephalopathy: Pathophysiology assumed in the first 3 years of the ongoing pandemic

“…Genetic studies also suggest a correlation between COVID-19 and AD. A study of the causal effect of COVID-19 on neurodegenerative diseases using the two-sample Mendelian randomization (MR) method revealed a correlation between AD and COVID-19, where COVID-19-infected phenotype was associated with a higher risk of AD [60] . Genetic variants were obtained from genome-wide association studies (GWAS), with summary-level data and meta-analyses.…”