Regional differences in the association of cytomegalovirus seropositivity and multiple sclerosis: A systematic review and meta-analysis

Abstract

© 2020 Elsevier B.V. Background: Despite of a few decades of investigations, the association and role of cytomegalovirus (CMV) and multiple sclerosis (MS) remain inconclusive. Herein, we performed a meta-analysis to investigate the association between CMV IgG serostatus and MS. Methods: A literature search was conducted on MEDLINE, EMBASE, and Cochrane databases. Eligibility criteria included observational studies assessing the seroprevalence of CMV immunoglobulin G (IgG) in adults with MS and non-MS control. Two authors screened all resulting studies and evaluated the quality of the included studies. Pooled odd ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effect model. Results: The search identified 771 unique citations, and 15 (3,591 MS patients and 4,241 controls) satisfied eligibility criteria. The meta-analysis of all included studies showed no significant association between CMV IgG seropositivity and MS with a substantial heterogeneity (OR 1.190; 95%CI 0.780–1.813; I2 32.7%). Subgroup analysis, stratified by geographic area, showed different associations and less heterogeneity in each geographical area. In Europe, CMV IgG seroprevalence was lower among people with MS than controls (OR 0.750; 95%CI 0.599–0.940; I213.9%). In contrast, CMV IgG seropositivity was more common among MS patients compared to controls in the Middle East region (OR 5.089; 95%CI 01.067–24.263; I2 5.6%). There was no significant association in North America. Conclusions: There is evidence of the regional differences in the association between CMV IgG seropositivity and MS. Further biological and epidemiological studies are needed to identify the genetic or environmental factors which are potentially the effect modifiers of this association.