Robust T cell responses in anti-CD20 treated patients following COVID-19 vaccination: a prospective cohort study

• Authors: Natacha Madelon, University of Geneva; Kim Lauper, University of Geneva; Gautier Breville, University of Geneva; Irène S Royo, University of Geneva; Rachel Goldstein, University of Geneva; Diego O Andrey, University of Geneva; Alba Grifoni, University of California; Alessandro Sette, University of California; Laurent Kaiser, University of Geneva; Claire-Anne Siegrist, University of Geneva; Axel Finckh, University of Geneva; Patrice H Lalive, University of Geneva; Arnaud M Didierlaurent, University of Geneva; Christiane S Eberhardt, Emory University
• Journal Title: CLINICAL INFECTIOUS DISEASES
• Publisher: Oxford University Press (OUP) | 2021-11-17
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1093/cid/ciab954
• Subjects: Health Sciences, Pathology; Health Sciences, Immunology
• Keywords: COVID-19 vaccination; T cell response; anti-CD20; B-cell depletion; multiple sclerosis; rheumatoid arthritis

Abstract

Background Patients treated with anti-CD20 therapy are particularly at risk of developing severe COVID-19, however little is known regarding COVID-19 vaccine effectiveness in this population. Methods This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n=37), compared to immunocompetent individuals (n=22). Results SARS-CoV-2-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4+ T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 + T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4 + and CD8 + T cells were polyfunctional but expressed more activation markers in patients than in controls. During follow-up, three MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination. Conclusions Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.