Response to COVID-19 booster vaccinations in seronegative people with MS

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.


Uncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and fingolimod, who have substantially reduced antibody responses to initial vaccine course.


To report humoral and T-cell responses following COVID-19 vaccine 3 in pwMS who were seronegative after COVID-19 vaccines 1&2.

Design, setting and participants:

PwMS taking part in a seroprevalence study without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Data on demographics, MS treatment, and COVID-19 infection/vaccine dates were derived from the medical notes.


Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. The relationship between evidence of prior COVID-19 infection and immune response to COVID-19 vaccine 3 was evaluated using Fishers exact test.


Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There no association between laboratory evidence of prior COVID-19 infection and anti-spike seroconversion following COVID-19 vaccine 3.


Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

Author list

Emma C Tallantyre, Martin J Scurr, Nicola Vickaryous, Aidan Richards, Valerie Anderson, David Baker, Randy Chance, Nikos Evangelou, Katila George, Gavin Giovannoni, Katherine Harding, Aimee Hibbert, Gillian Ingram, Stephen Jolles, Meleri Jones, Angray Kang, Samantha Loveless, Stuart Moat, Neil Robertson, Francesca Rios, Klaus Schmierer, Mark Willis, Andrew Godkin, Ruth Dobson

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