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 Oct:55:103157. doi: 10.1016/j.msard.2021.103157. Epub 2021 Jul 21.

Abstract

Background: Disease modifying therapies for multiple sclerosis (MS) can impair the specific immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Specifically, it is recognized that ocrelizumab reduces or abrogates anti-SARS-CoV-2 antibody production after natural infection or vaccination, while very little is known about T-cell responses.

Methods: We developed an interferon (IFN)-γ release assay (IGRA) to detect T-cell responses specific to SARS-CoV-2 after overnight stimulation of whole blood with peptide libraries covering the immunodominant sequence domains of the Spike glycoprotein (S) and the Nucleocapsid phosphoprotein (N).

Results: Five patients with MS receiving ocrelizumab treatment for at least 1 year and recovered from SARS-CoV-2 infection were enrolled in the study. Despite the absence or the very low concentration of anti-S antibodies, a T-cell response was detectable in all the five MS patients. These results are in accordance with the marked reduction of peripheral B-lymphocyte absolute counts induced by ocrelizumab, that, conversely, did not affect peripheral blood T-lymphocyte subset absolute and relative counts and CD4/CD8 ratio.

Conclusions: 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.

Keywords: CD20; Disease modifying therapies; IGRA; Interferon-gamma; Stimulation; T-lymphocyte, peptides.

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antibodies, Viral / blood
  • COVID-19* / immunology
  • Humans
  • Multiple Sclerosis* / drug therapy
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ocrelizumab