Preserved T Cell Responses to SARS-CoV-2 in Anti-CD20 Treated Multiple Sclerosis

Background: Optimal management of anti-CD20-treated patients with multiple sclerosis (pwMS) is an important clinical task during the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic.

Objectives: To characterize humoral and cellular immune responses to SARS-CoV-2 vaccinations/infections in a longitudinal cohort of anti-CD20 treated ( = 175) and anti-CD20 therapy-naïve ( = 41) pwMS.

Methods: Anti-SARS-CoV-2 spike protein immunoglobulin G (IgG) and IgA, virus neutralizing capacity, IgG avidity and SARS-CoV-2-specific T cells were determined.

Results: Following two SARS-CoV-2 vaccinations, not only SARS-CoV-2 spike protein IgG and IgA, but also neutralizing capacity and avidity of SARS-CoV-2 IgG were lower in anti-CD20-treated ( = 51) than in anti-CD20 therapy-naïve pwMS ( = 14) and in healthy controls (HC,  = 19). However, in all anti-CD20-treated pwMS vaccinated twice ( = 26) or infected with SARS-CoV-2 ( = 2), in whom SARS-CoV-2-specific T cells were measured, SARS-CoV-2-specific T cells were detectable, at levels similar to those of twice-vaccinated anti-CD20 therapy-naïve pwMS ( = 7) and HC ( = 19). SARS-CoV-2-S1 IgG levels ( = 0.42,  = 0.002), antibody avidity ( = 0.7,  < 0.001), and neutralizing capacity ( = 0.44,  = 0.03) increased with time between anti-CD20 infusion and second vaccination. Based on detection of SARS-CoV-2 antibodies, SARS-CoV-2 infections occurred in 4 out of 175 (2.3%) anti-CD20-treated pwMS, all of whom recovered fully.

Conclusions: These findings should inform treatment decisions and SARS-CoV-2 vaccination management in pwMS.