PT  - JOURNAL ARTICLE
AU  - Frederik Novak
AU  - Hamza Mahmood Bajwa
AU  - John Eugenio Coia
AU  - Anna Christine Nilsson
AU  - Christian Nielsen
AU  - Dorte K Holm
AU  - Kamilla Østergaard
AU  - Mathilde Vilhelmine Miller Hvidt
AU  - Keld-Erik Byg
AU  - Isik S Johansen
AU  - Kristen Mittl
AU  - William Rowles
AU  - Scott S Zamvil
AU  - Riley Bove
AU  - Joseph J Sabatino, Jr
AU  - Tobias Sejbaek
TI  - Low protection from breakthrough SARS-CoV-2 infection and mild disease course in ocrelizumab-treated patients with multiple sclerosis after three mRNA vaccine doses
AID  - 10.1136/jnnp-2022-330757
DP  - 2023 Apr 25
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - jnnp-2022-330757
4099  - http://jnnp.bmj.com/content/early/2023/04/24/jnnp-2022-330757.short
4100  - http://jnnp.bmj.com/content/early/2023/04/24/jnnp-2022-330757.full
AB  - Background Our study investigated the rate of breakthrough SARS-CoV-2 infection and clinical outcomes in a cohort of multiple sclerosis (MS) patients who were treated with the anti-CD20 monoclonal antibody (Ab), ocrelizumab, before first, second and third BNT162b2 mRNA vaccinations. To correlate clinical outcomes with the humoral and cellular response.Methods The study was a prospective non-randomised controlled multicentre trial observational study. Participants with a diagnosis of MS who were treated for at least 12 months with ocrelizumab prior to the first BNT162b2 mRNA vaccination were prospectively followed up from January 2021 to June 2022.Results Out of 54 participants, 32 (59.3%) developed a positive SARS-CoV-2 PCR test in the study period. Mild infection was observed in all infected participants. After the third vaccination, the non-infected participants had higher mean Ab levels compared to the infected participants (54.3 binding antibody unit (BAU)/mL vs 26.5 BAU/mL, p=0.030). The difference in reactivity between spike-specific CD4+ and CD8+ T lymphocytes in the two groups was not significant.Conclusion and relevance The study results demonstrate rates of 59% in breakthrough infections after the third SARS-CoV-2 mRNA vaccination in ocrelizumab-treated patients with MS, without resulting in critical disease courses. These findings suggest the need for continuous development of prophylactic treatments when proved important in the protection of severe breakthrough infection.