T-Cell Responses Still Detected in Patients With MS Receiving Ocrelizumab and Recovered From COVID-19


Patients with multiple sclerosis (MS) who have recovered from COVID-19 and received the B-cell depleting therapy ocrelizumab for at least 1 year were observed to still have T-cell responses.

Patients with multiple sclerosis (MS) who have undergone therapy with ocrelizumab (Ocrevus) and have recovered from COVID-19 still had detectable T-cell responses, according to a recent study published in Multiple Sclerosis and Related Disorders.

The study provides insight into whether B-cell depleting treatment for MS impairs a patient’s immune responses to SARS-CoV-2, the virus that causes COVID-19.

“The detection of specific T-cell responses to SARS-CoV-2 in patients receiving B-cell depleting therapies represents a useful tool to improve the diagnostic approach in SARS-CoV-2 infection and to accurately assess the immunological response after natural infection or vaccination,” wrote the investigators.

Ocrelizumab, a B-cell depleting treatment, is known to reduce or abrogate anti–SARS-CoV-2 antibody production after a patient is naturally infected with the virus or receives a vaccine. However, there is little evidence on how the drug affects cell-mediated responses in response to COVID-19 infection. Some case reports have shown that detectable anti–SARS-CoV-2 antibodies are absent and others have demonstrated poor seroconversion rates after receiving a COVID-19 vaccine in patients with MS receiving B-cell depleting therapy.

Five patients who had recovered from COVID-19, 4 of whom were men, with a median (range) age of 33 (27-50) years were enrolled in the analysis. All patients had relapsing remitting MS and had been exposed to ocrelizumab for at least 1 year. The median (range) Expanded Disability Status Score was 0.5 (0-3). Additionally, 2 patients were hospitalized for COVID-19–related pneumonia and were classified as having severe COVID-19.

Interferon (IFN)-γ release assay, developed by the investigators, is a tool used to identify individuals with specific cellular immunity for COVID-19. Samples from the patients were collected after a median (range) of 89 (66-176) days after onset of COVID-19 and 89 (36-196) days from their last infusion of ocrelizumab.

“SARS-CoV-2 IGRA assay could be a valuable tool for implementing the accuracy of diagnosis of COVID-19, especially in those subjects receiving B-cell depleting treatments. Moreover, it may represent an integrative approach to correctly establish the efficacy of vaccination in patients receiving immunosuppressants targeting the B-cell compartment.,” the investigators noted.

Anti–surface glycoprotein antibodies, which target the spike protein (S) associated with SARS-CoV-2, were detectable in 2 subjects at low concentrations (patient 1, 0.54 U/mL; patient 5, 155.6 U/mL). Analysis of peripheral blood using flow cytometry revealed that the patients had a reduction in CD19+ B-lymphocyte absolute and relative counts, demonstrating a median (range) of 1 (0-15) cell/mcL and 0.04% (0%-0.96%), respectively.

However, the patients had normal CD4+ T-cell absolute and relative counts. This trend was also observed for patients’ CD8+ T-cell absolute and relative counts. Additionally, the ratio of CD4 and CD8 T cells was above 1 for all 5 patients.

Through whole blood stimulation of the spike protein, the investigators were unable to detect IFN-γ levels. After stimulation of the nucleocapsid phosphoprotein (N) and the N-terminal S1 domain (S1) of the spike protein on SARS-CoV-2, the investigators detected levels of IFN-γ in 4 patients. After pooling together peptide libraries of S1, S, and N, production of IFN-γ was detectable in all subjects.

“Whole blood stimulation with the same type of SARS-CoV-2 peptides libraries used in our experiment, has shown high sensitivity and specificity to diagnose and distinguish different SARS-CoV-2 exposures,” the investigators said.

A main limitation of the study involved the lack of samples from before the patients were infected with SARS-CoV-2. Thus, the investigators were unable to evaluate SARS-CoV-2 specific T-cell responses prior to the patients developing COVID-19.

“Further studies are needed, involving larger cohorts of immunocompromised subjects, to confirm the role of T-cell responses during SARS-CoV-2 acute infection and after vaccination,” wrote the investigators.


Iannetta M, Landi D, Cola G, et al. T-cell responses to SARS-CoV-2 in multiple sclerosis patients treated with ocrelizumab healed from COVID-19 with absent or low anti-spike antibody titers. Mult Scler Relat Disord. 2021;33:103157. doi: 10.1016/j.msard.2021.103157

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