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ImportanceThe SARS-CoV-2 variant Omicron escapes neutralizing antibody responses elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third dose of vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses. ObjectiveTo determine T-cell responses to the Spike (S)-protein of Omicron in anti-CD20 treated patients before and after their third mRNA COVID-19 vaccination DesignProspective observational monocentric study SettingConducted since March 2021 at the University Hospital Geneva ParticipantsTwenty adults with multiple sclerosis on anti-CD20 treatment (ocrelizumab) who received their third dose of mRNA COVID-19 vaccine 6 to 7 months after their second vaccination. Intervention: Blood sampling before and one month after the third vaccine dose Main outcomes and measuresQuantification of CD4 and CD8 (cytotoxic) T cells specific for SARS-CoV-2 S-protein of vaccine strain, Delta and Omicron variants, using activation marker induced assay (AIM) and comparing frequencies before and after the third vaccine dose. ResultsS-specific CD4 and CD8 T-cell memory against all variants was maintained in around half of the patients six months after their second vaccination, albeit at lower frequencies against Delta and Omicron variants. A third dose enhanced the number of responders to all variants and significantly increased CD8 T-cell responses. The frequencies of T cells specific to Omicron and Delta remained lower than those specific to the vaccine strain after the boost. Conclusion and relevanceVaccinated MS patients on anti-CD20 treatment show robust T-cell responses that recognize S from the circulating Delta and Omicron variants. Response rates increased after the third dose, demonstrating that a booster dose might improve cytotoxic T-cell mediated protection against severe disease in patients with low humoral response. The clinical relevance of the reduced frequencies of T cells specific to Omicron will need to be monitored in the future. Key pointsO_ST_ABSQuestionC_ST_ABSAre T-cell responses to Omicron variant conserved in anti-CD20 treated MS patients after COVID-19 mRNA vaccination? FindingsOmicron Spike-specific CD4 and CD8 T cells were detectable in around half of twenty patients six months after the second COVID-19 vaccine dose, and cytotoxic T-cell responses increased following the third dose. Frequencies of T cells specific against the S-protein of Delta and Omicron were lower compared to the vaccine strain, both before and after boost. MeaningIn anti-CD20-treated MS patients the vaccine-induced T-cell responses are little affected by the mutations carried by Omicron, and a third vaccine dose improves cytotoxic T-cell responses.
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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. This study assesses humoral and T-cell responses to 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). 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%). Vaccine-specific CD4+ and CD8+ T cells were polyfunctional but expressed more IL-2 in patients than in controls. In summary, 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 prevention of severe COVID-19.
