Anti-SARS-CoV-2 T-stem cell memory persists in ocrelizumab-treated MS patients

Gisella Guerrera, Alessandra Mandelli, Annamaria Finardi, Mario Orrico, Silvia D’Orso, Mario Picozza, Maddalena Noviello, Valeria Beretta, Bruno Bonetti, Massimiliano Calabrese, Damiano Marastoni, Nicola De Rossi, Ruggero Capra, Marco Salvetti, Maria Chiara Buscarinu, Matilde Inglese, Antonio Uccelli, Lucia Moiola, Catarina Raposo, Erwan Muros-Le RouzicRosetta Pedotti, Massimo Filippi, Chiara Bonini, Luca Battistini, Giovanna Borsellino, Roberto Furlan

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Development of long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) T-cell responses in persons with multiple sclerosis (pwMS) treated with ocrelizumab is questioned. Objective: Investigate antiviral T-cell responses after infection with SARS-CoV-2 in ocrelizumab-treated pwMS. Control groups included ocrelizumab-treated pwMS without SARS-CoV-2 infection, and non-MS individuals with and without SARS-CoV-2 infection. Methods: Peripheral blood mononuclear cells were stimulated with SARS-CoV-2 peptide pools and T-cell reactivity was assessed by ELISPOT for interferon (IFN)-γ detection, and by multiparametric fluorescence-activated cell sorting (FACS) analyses for assessment and characterization of T-cell activation. Results: ELISPOT assay against the spike and the N protein of SARS-CoV-2 displayed specific T-cell reactivity in 28/29 (96%) pwMS treated with ocrelizumab and infected by SARS-CoV-2, similar to infected persons without MS. This reactivity was present 1 year after infection and independent from the time of ocrelizumab infusion. FACS analysis following stimulation with SARS-CoV-2 peptide pools showed the presence of activation-induced markers (AIMs) in both CD4+ and CD8+ T-cell subsets in 96% and 92% of these individuals, respectively. Within naïve AIM+ CD4+ and CD8+ T-cells, we detected T memory stem cells, suggesting the acquisition of long-term memory. Conclusions: B-cell depletion using ocrelizumab does not impair the development of long-lasting anti-SARS-CoV-2 T-cell responses.

Original languageEnglish
Pages (from-to)1937-1943
Number of pages7
JournalMultiple Sclerosis Journal
Issue number12
StatePublished - Oct 2022
Externally publishedYes


  • COVID-19
  • SARS-CoV-2
  • anti-CD20
  • cellular immune response
  • multiple sclerosis
  • ocrelizumab


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