Immune responses to SARS‐CoV‐2 vaccination in multiple sclerosis: a systematic review/meta‐analysis

INTRODUCTION: Responses to SARS‐CoV‐2 vaccination in patients with MS (pwMS) varies by disease‐modifying therapies (DMTs). We perform a meta‐analysis and systematic review of immune response to SARS‐CoV‐2 vaccines in pwMS. METHODS: Two independent reviewers searched PubMed, Google Scholar, and Embase from January 1, 2019‐December 31, 2021, excluding prior SARS‐CoV‐2 infections. The meta‐analysis of observational studies in epidemiology (MOOSE) guidelines were applied. The data were pooled using a fixed‐effects model. RESULTS: Eight‐hundred sixty‐four healthy controls and 2203 pwMS from 31 studies were included. Antibodies were detected in 93% healthy controls (HCs), and 77% pwMS, with >93% responses in all DMTs (interferon‐beta, glatiramer acetate, cladribine, natalizumab, dimethyl fumarate, alemtuzumab, and teriflunomide) except for 72% sphingosine‐1‐phosphate modulators (S1PM) and 44% anti‐CD20 monoclonal antibodies (mAbs). T‐cell responses were detected in most anti‐CD20 and decreased in S1PM. Higher antibody response was observed in mRNA vaccines (99.7% HCs) versus non‐mRNA vaccines (HCs: 72% inactivated virus; pwMS: 86% vector, 59% inactivated virus). A multivariate logistic regression model to predict vaccine response demonstrated that mRNA versus non‐mRNA vaccines had a 3.4 odds ratio (OR) for developing immunity in anti‐CD20 (p = 0.0052) and 7.9 OR in pwMS on S1PM or CD20 mAbs (p < 0.0001). Antibody testing timing did not affect antibody detection. CONCLUSION: Antibody responses are decreased in S1PM and anti‐CD20; however, cellular responses were positive in most anti‐CD20 with decreased T cell responses in S1PM. mRNA vaccines had increased seroconversion rates compared to non‐RNA vaccines. Further investigation in how DMTs affect vaccine immunity are needed.