For a study, researchers sought to assess the effect of disease-modifying treatments (DMTs) for multiple sclerosis (MS) on the establishment of cellular and humoral immunity to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. About 18 to 60-year-old MS patients were evaluated for anti-nucleocapsid and anti-Spike receptor-binding domain (RBD) antibodies with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture enzyme-linked immunosorbent assay (ELISA); and IL-2 and IFNγ ELISpot assays.  Comparing assay results by DMT class. Spearman correlation and multivariate analysis examined relationships between immunologic responses and infection severity. Between January 6, 2021, and July 21, 2021, 389 MS patients (mean age 40,3 years; 74% women; 62% non-White) were enrolled. About 40% of patients were treated with ocrelizumab (OCR), —17% with natalizumab, −12% with Sphingosine 1-phosphate receptor (S1P) modulators, and 15% remained untreated. Around 177 patients (46%) exhibited test evidence of SARS-CoV-2 infection; 130 had a symptomatic illness, and 47 had a silent infection. Antibody responses were significantly less in OCR than in other groups (P≤0.0001). T-cell responses (IFNγ) were lower in S1P (P=0.03), higher in natalizumab (P<0.001), and comparable in other DMTs, including OCR. The correlation between cellular and humoral responses were moderate in both OCR (r=0.45, P=0.0002) and non-OCR (r=0.64, P<0.0001). Immune responses did not vary according to race or ethnicity. The clinical course of Coronavirus disease 2019 (COVID-19) was generally mild and comparable to DMTs; 7% (9/130) of patients were hospitalized. The impact of DMTs on the humoral and cellular immune responses to SARS-CoV-2 infection varied. In this relatively youthful and able-bodied MS patient population, there was no correlation between immune responses and COVID-19 clinical severity.