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Antibody responses after SARS-CoV-2 infection were reduced in multiple sclerosis (MS) patients on ocrelizumab (Ocrevus) compared with other MS patients, but T-cell responses were not, preliminary data from a New York study suggested.

Antibody detection varied but T-cell levels were similar for patients with COVID-19 and MS regardless of the disease-modifying treatment they used, reported Ilya Kister, MD, of NYU Langone Health in New York City, at the session of the American Academy of Neurology virtual meeting.

"The top-line result of our study is that MS patients on B-cell depleting therapy, ocrelizumab, have attenuated antibody responses to SARS-CoV-2 virus and are much less likely than MS patients not on ocrelizumab to produce neutralizing antibodies against SARS-CoV-2," Kister said.

"On the other hand, SARS CoV-2-specific T-cell responses were similar in ocrelizumab-treated and non-ocrelizumab-treated patients and clinically, these two groups had COVID of similar severity," he told 名媛直播. "These findings suggest that ocrelizumab-treated patients are able to fight off COVID-19 infection despite depressed antibody responses, presumably because other arms of the immune system -- T-cells and innate immunity -- provide adequate protection in the majority of cases."

"It's reassuring to see T-cell responses to SARS-CoV-2 in patients on a B-cell depleting monoclonal antibody treatment," noted Barry Singer, MD, of Missouri Baptist Medical Center in St. Louis, who wasn't involved with the research.

"The study design provides a template to study COVID-19 vaccination responses in multiple sclerosis patients with assessments of anti-spike antibodies and T-cell responses. The ultimate, unanswered question for many living with multiple sclerosis on disease-modifying therapies is whether their COVID-19 vaccination was protective," Singer told 名媛直播.

Kister and colleagues evaluated MS patients at NYU infected with SARS-CoV-2 during the first wave of the COVID-19 pandemic early in 2020. Participants had antibody and T-cell assessments in January-March 2021, an average of 260 days after infection. MS patients who had a COVID-19 vaccine, who were using anti-CD20 drugs other than ocrelizumab, who had high-dose steroids, intravenous immunoglobulin (IVIG), plasma, or antibody treatments in the past 3 months, or who had a major comorbidity that could suppress the immune system were excluded.

About one-third (36%) of patients were treated with ocrelizumab and 16% were untreated. Participants had an average age of 41 and 70% were female. They had MS for an average of 11.5 years and 86% had relapsing MS. Most were fully ambulatory.

A total of 59 patients in the group had laboratory-confirmed SARS-CoV-2. Assessments for these patients included three antibody tests: the Elecsys anti-SARS-CoV-2 (Roche Diagnostics) and NYU multiplex bead-based immunoassays of antibody responses to SARS-CoV-2 nucleocapsid and spike proteins, and a live virus immunofluorescence-based microneutralization assay. Some patients also had T-cell response studies including enzyme-linked immune absorbent spot (ELISpot) cytokine assays and SARS-CoV-2 TruCulture.

The NYU multiplex assay detected antibodies to SARS-CoV-2 in most MS patients regardless of treatment, but levels of IgG anti-spike antibodies were significantly lower in patients treated with ocrelizumab versus those using other disease-modifying treatments or no MS treatment at all. The median half-maximal inhibitory concentration (IC50) of neutralizing antibodies was lower in the ocrelizumab-treated group than others. T-cell responses by ELISpot and TruCulture had similar rates in both ocrelizumab-treated and non-ocrelizumab-treated patients.

"One problem is we don't have easy access to T-cell response tests," noted John Corboy, MD, of the University of Colorado School of Medicine in Denver, who wasn't involved with this study. "But it is reassuring that there are responses, albeit lower with antibodies."

The University of Colorado and NYU Langone Health will start patients soon, Corboy added. "We plan to conduct a longitudinal study of how ocrelizumab-treated patients generate T-cell and antibody immune responses to COVID-19 vaccine in collaboration with the Colorado group," Kister said. "This study will enroll 60 patients and follow them for a year."

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