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ImportanceData on immune responses following SARS-CoV-2 vaccinations/infections and on detection rate of SARS-CoV-2 infections in anti-CD20 treated patients with multiple sclerosis (pwMS) are important for guiding management of pwMS during the current SARS-CoV-2 pandemic. ObjectiveTo analyze humoral and cellular immune responses to SARS-CoV-2 vaccinations/infections and to determine the detection rate of SARS-CoV-2 infections in anti-CD20 treated pwMS. DesignProspective single-center cohort study from March 2020 to August 2021. SettingMS referral center, Charite - Universitatsmedizin Berlin, Germany. Participants222 consecutive pwMS (128 [57.7%] female, median [range] age 39 [17-81] years). 181 patients were on anti-CD20 therapy at study inclusion, 41 began anti-CD20 therapy during the study. Hospital employees (HE, n=19) served as controls. ExposurespwMS were exposed to anti-CD20 therapy for 169.5 patient years. 51 patients under anti-CD20 treatment, 14 patients before anti-CD20 treatment, and 19 HE were vaccinated twice against SARS-CoV-2. Main outcomesSARS-CoV-2 spike protein immunoglobulin (Ig)G (ELISA and immunofluorescence), IgA (ELISA), IgG to four recombinant SARS-CoV-2 antigens (solid phase immunoassay), neutralizing capacity of SARS-CoV-2 antibodies (plaque reduction neutralization test), SARS-CoV-2 IgG avidity (modified ELISA), and SARS- CoV-2 specific T cells (interferon-{gamma} release assay). ResultsFollowing two SARS-CoV-2 vaccinations, median (IQR) levels of SARS-CoV-2 spike protein IgG (OD ratio: 1.2 [0.1-5.1] vs. 9.0 [6.8-9.9] vs. 8.8 [8.0-9.4], p |