Antibody response to four doses of SARS-CoV-2 vaccine in rare autoimmune rheumatic diseases: an observational study

Objective Antibody responses to coronavirus disease 2019 (COVID-19) vaccines are reduced among immunocompromised patients but are not well quantified among people with rare disease. We conducted an observational study to evaluate the antibody responses to the booster SARS-CoV-2 vaccine in people with rare autoimmune rheumatic diseases (RAIRD).Methods Blood samples were collected after second, before third, after third and after fourth vaccine doses. Anti-spike and anti-nucleocapsid antibody levels were measured using an in-house ELISA. Logistic regression models were built to determine the predictors for non-response. Results were compared with age- and sex-matched healthy controls.Results Forty-three people with RAIRD were included, with a median age of 56 years. Anti-spike seropositivity increased from 42.9% after second dose to 51.2% after third dose and 65.6% after fourth dose. Median anti-spike antibody levels increased from 33.6 (interquartile range 7.8-724.5) binding antibody units after second dose to 239.4 (interquartile range 35.8-1051.1) binding antibody units after the booster dose (third dose, or fourth dose if eligible). Of the participants who had sufficient antibody levels post-second dose, 22.2% had insufficient levels after the booster, and 34.9% of participants had lower antibodies after the booster than the lowest healthy control had after the second dose. Rituximab in the 6 months prior to booster (P = 0.02) and non-White ethnicity (P = 0.04) were associated with non-response. There was a dose-response relationship between the timing of rituximab and generation of sufficient antibodies (P = 0.03).Conclusion Although the booster dose increased anti-spike IgG and seropositivity rates, some people with RAIRD, particularly those on rituximab, had insufficient antibody levels despite three or four doses. What does this mean for patients?People living with rare autoimmune rheumatic illnesses, such as vasculitis, lupus, myositis and scleroderma, can have a weakened immune system because of their illness or its treatment. They might not respond to coronavirus disease 2019 (COVID-19) vaccinations as effectively as healthy people. Forty-three people with a rare autoimmune rheumatic illness took part (30 had vasculitis, 8 systemic lupus erythematosus and 5 myositis). We used a questionnaire to collect health information including diagnosis, treatments, age, sex, ethnic origin and details about COVID-19 vaccination and infection. We collected blood samples after the first booster vaccine, which was the third or fourth COVID-19 vaccine. We looked for anti-spike antibodies in the blood samples (a sign of response to the vaccine). We used the lowest level of antibodies produced by a group of healthy people to define having enough antibodies. We found that: 65% of people living with a rare autoimmune disease made enough antibodies after their first booster dose of vaccine; more vaccines increased the chance of having protective antibodies (enough antibodies were found in 43% of people after their second dose, 51% after their third dose and 66% after their fourth dose); and having a drug called rituximab in the 12 months before vaccination and being from a non-White ethnic background reduced the chance of producing enough antibodies.