T-cell response and COVID-19 infection following COVID-19 booster vaccinations in pwMS treated with ocrelizumab

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Introduction People with multiple sclerosis (pwMS) treated with ocrelizumab mount a T-cell response to vaccination, irrespective of humoral response. Correlates of this pattern of immune response remain unclear. Methods PwMS on ocrelizumab who were seronegative following initial COVID-19 vaccine course provided whole blood samples 2-8 weeks after vaccines 3 (n=30) and 4 (n=15). T-cell responses to SARS- CoV-2 spike protein (IFNγ release assay), anti-spike IgG, and anti-nucleocapsid IgG were measured. Clinical data including COVID-19 PCR/lateral flow test results, and infection severity were recorded. Results 26/30 (86.7%) people showed measurable T-cell responses following COVID-19 vaccine 3, 13/15 (87%) after vaccine 4. 12/30 (40.0%) had detectable anti-spike IgG following vaccine 3. Of the 15 who gave samples at both timepoints, 5/15 (33.3%) were seropositive after vaccine 3 and 4/15 (26.7%) following vaccine 4. Rates of anti-spike IgG at vaccine 3 were 6/8 (75.0%) where there was evidence of prior COVID-19 (nucleocapsid IgG, PCR, or lateral flow test), and 6/22 (27.3%) where there was no evidence of prior infection (chi-squared; p=0.0183). Four pwMS had COVID-19 infection between vaccines 3 and 4, none required hospitalisation. All had a T-cell response at vaccine 3 and two had detectable anti-spike IgG. Conclusions Many pwMS who were seronegative following the initial COVID-19 vaccine course show T- cell responses following booster vaccination. The lack of severe infections is relatively reassuring.

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