COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study

Abstract

Emerging evidence has suggested a close correlation between COVID-19 and neurodegenerative disorders. However, whether there exists a causal association and the effect direction remains unknown. To examine the causative role of COVID-19 in the risk of neurodegenerative disorders, we estimated their genetic correlation, and then conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of susceptibility, hospitalization, and severity of COVID-19, as well as six major neurodegenerative disorders including Alzheimer’s disease (AD), amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body dementia, multiple sclerosis, and Parkinson’s disease. We identified a significant and positive genetic correlation between hospitalization of COVID-19 and AD (genetic correlation: 0.23, P = 8.36E–07). Meanwhile, hospitalization of COVID-19 was significantly associated with a higher risk of AD (OR: 1.02, 95% CI: 1.01–1.03, P: 1.19E–03). Consistently, susceptibility (OR: 1.05, 95% CI: 1.01–1.09, P: 9.30E–03) and severity (OR: 1.01, 95% CI: 1.00–1.02, P: 0.012) of COVID-19 were nominally associated with higher risk of AD. The results were robust under all sensitivity analyses. These results demonstrated that COVID-19 could increase the risk of AD. Future development of preventive or therapeutic interventions could attach importance to this to alleviate the complications of COVID-19.

Acute TNFα levels predict cognitive impairment 6–9 months after COVID-19 infection

“…One emerging hypothesis following observations of persistent long-term cognitive difficulties and physiological patterns after COVID-19 suggests a potential trigger or accelerator of neurodegenerative process ( Beauchet and Allali, 2022 , McAlpine et al, 2021 ). Indeed, different studies have shown that COVID-19 associates with neurotoxicity, hippocampal degeneration, and increased risk of Alzheimer's disease ( Bayat et al, 2022 , Chiricosta et al, 2021 , Li et al, 2022 ). However, although the hypothesis of an initiation (or acceleration) of neurodegenerative cascades is central after COVID-19 infection, other hypotheses that limbic encephalitis after COVID-19 ( Franke et al, 2023 , Franke et al, 2021 ) would result in persistent cognitive symptoms could potentially be another interesting avenue (Shnayder et al, 2021).…”

Cognitive dysfunction associated with COVID-19: Prognostic role of circulating biomarkers and microRNAs

“…As the population of patients recovering from COVID-19 grows, it is important to establish an understanding of the multi-organ dysfunction associated with post-COVID-19 complications. Of note, neurological manifestations in COVID-19 patients have been reported, showing a close correlation between COVID-19 and future development of neurodegenerative diseases (Wu et al, 2020b;Taquet et al, 2021;Frontera et al, 2022;Li et al, 2022a). It has also been established that the likelihood of developing COVID-19-associated cognitive impairment and the severity of these deficits is associated with the severity of the SARS-CoV-2 infection and the subsequent increases in specific circulating inflammatory mediators and biomarkers (Becker et al, 2021;Miskowiak et al, 2021;Zeng et al, 2022).…”

Selective Vulnerability of the Locus Coeruleus Noradrenergic System and its Role in Modulation of Neuroinflammation, Cognition, and Neurodegeneration

“…The direct viral infection of the brain has also been proposed as a cause for these symptoms, as SARS-CoV-2 viral proteins were detected in the brain tissue of patients who died from COVID-19 ( Matschke et al, 2020 ). It has been suggested that increased COVID-19 susceptibility and severity could increase the risk for neurodegenerative disorders ( Li et al, 2022 ). While further investigations are required to clarify a causal link, these collective findings demonstrate the importance of understanding the neurodegenerative sequelae of viral infections.…”