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Meta-Analysis
. 2025 Oct 10;15(1):388.
doi: 10.1038/s41398-025-03639-2.

Viral infections and the risk of neurodegenerative diseases: a comprehensive meta-analysis and systematic review

Ru-Yin Liu  1 , Kang-Fu Yin  1 , Sheng-Yi He  1 , Wei-Ming Su  1 , Qing-Qing Duan  1 , Xiang-Jin Wen  1 , Ting Chen  1 , Cong Shen  2 , Ju-Rong Li  2 , Bei Cao  3 , Yong-Ping Chen  4
Affiliations
Meta-Analysis

Viral infections and the risk of neurodegenerative diseases: a comprehensive meta-analysis and systematic review

Ru-Yin Liu et al. Transl Psychiatry. .

Abstract

Background: Viral infections have been implicated in the pathogenesis of neurodegenerative diseases (NDs); however, evidence linking specific viruses to Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) remains inconclusive. This study conducted a meta-analysis and systematic review to investigate these associations.

Methods: Thorough searches were conducted across Embase, PubMed, Cochrane Library, Web of Science and Scopus until May 18, 2025, to identify observational studies investigating the relationship between viral infections and the risk of NDs, including AD, PD, and ALS. Meta-analyses were executed using a random-effects model with Stata MP18.0.

Results: A total of 34,417 articles were identified, of which 73 met the eligibility criteria for inclusion in the meta-analysis, and 48 were included in the systematic review. The analysis demonstrated that infections with cytomegalovirus (CMV) (odds ratio [OR] = 1.41; 95% confidence interval [CI]: 1.03, 1.93), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (OR = 1.88; 95% CI: 1.53, 2.32), hepatitis C virus (HCV) (OR = 1.39; 95% CI: 1.14, 1.69), and human herpesvirus (HHV) (OR = 1.24; 95% CI: 1.02, 1.51) were associated with an increased risk of AD. Regarding PD, infections with hepatitis B virus (HBV) (OR = 1.18; 95% CI: 1.04, 1.35) and HCV (OR = 1.29; 95% CI: 1.18, 1.41) were identified as risk factors. Conversely, no significant correlation was found between any viral infection and the risk of ALS.

Conclusion: This meta-analysis supports the role of select viral infections in AD and PD pathogenesis. However, no association was found between viral infections and ALS, warranting further large, multicenter, and longitudinal studies to elucidate mechanisms and confirm causality.

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Conflict of interest statement

Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Consent for publication: All the authors have consented to publication.

Figures

Fig. 1
Fig. 1. Search flow diagram for included studies in the meta-analysis.
N, n: Number of study.
Fig. 2
Fig. 2. Proportion of NOS scores for records included in the systematic review and meta- analysis.
NOS scores were divided into 3 groups high risk of bias (0 ~ 3), moderate risk of bias (4 ~ 6), low risk of bias (7 ~ 9). NOS, Newcastle-Ottawa Scale; n, Number of study.
Fig. 3
Fig. 3. Meta-analysis of studies exploring the association between viral infections and AD.
OR: odds ratio; CI: confidence interval; HSV-1/2: Herpes Simplex Virus Type 1/2; VZV: Varicella-Zoster Virus; CMV: Cytomegalovirus; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; HCV: Hepatitis C Virus; HHV: Human Herpesvirus. *Calculated by the author.
Fig. 4
Fig. 4. Meta-analysis of studies exploring the association between viral infections and PD.
OR: odds ratio; CI: confidence interval; VZV: Varicella-Zoster Virus; MeV: Measles Virus; CMV: Cytomegalovirus; IFV: Influenza virus; MuV: Mumps virus; HSV: Herpes Simplex Virus; HBV/HCV: Hepatitis B/C Virus. *Calculated by the author.
See this image and copyright information in PMC

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