Background: Multiple Sclerosis (MS) is a chronic autoimmune disease, affecting over 2.5 million people worldwide. There has been growing concern about the impact of COVID-19 on the clinical course of MS. However, these findings remain controversial, and there is a lack of high-quality evidence to establish the relationship between COVID-19 and MS.

Methods: A comprehensive search was done to identify relevant studies reporting relapse rate in patients with MS (pwMS), those comparing the relapse rate of COVID-19 pwMS and MS controls, and studies investigating the effect of COVID-19 on relapse rate of pwMS. The results were presented as proportion of COVID-19 pwMS experiencing relapse and odds ratio determining the impact of COVID-19 on relapse rate.

Results: Fourteen studies were included in the analyses. The proportion of COVID-19 positive pwMS with relapse was 7.71 per 100 cases (95 % confidence interval, CI: 4.41-13.89, I2=96 %). Quantitative evaluation of studies with pwMS without COVID-19 did not demonstrate a statistically significant difference in relapse rate of patients with COVID-19 (OR: 0.75, 95 %CI: 0.44-1.29, I2= 54 %). Subgroup and sensitivity analyses did not alter the lack of significance of association between COVID-19 and MS relapse. Sensitivity analysis excluding the outlying study was largely in favor of no difference between the groups (OR:1.00, 95 %CI: 0.72-1.38, I2=34 %)

Conclusion: The results of this review does not suggest that COVID-19 influences the relapse rate in pwMS. While the findings alleviate the concerns regarding the co-occurrence of the diseases, further studies are needed to investigate the effects of confounding factors.