Antibody prevalence after 3 or more COVID-19 vaccine doses in 23,000 immunosuppressed individuals: a cross-sectional study from MELODY

Objectives To investigate the prevalence of spike-protein antibodies following at least 3 COVID-19 vaccine doses in immunocompromised individuals. Design Cross-sectional study using UK national disease registries of individuals with solid organ transplants (SOT), rare autoimmune rheumatic diseases (RAIRD) and lymphoid malignancies (LM). Setting Participants were identified, invited and recruited at home by accessing the NHS Blood and Transplant Registry for those UK individuals who had received a SOT; and the National Disease Registration Service at NHS Digital for identifying individuals within England with RAIRD or LM. Participants 101972 people were invited, 28411 recruited, and 23036 provided serological data, comprising 9927 SOT recipients, 6516 with RAIRD, and 6593 with LM. Interventions Participants received a lateral flow immunoassay for spike-protein antibodies to perform at home together with an online questionnaire. Main outcome measures Odds of detectable IgG spike-protein antibodies in immunosuppressed cohorts following at least three COVID-19 vaccine doses by participant demographic, disease type, and treatment related characteristics Results IgG spike-protein antibodies were undetectable in 23.3%, 14.1% and 20.7% of the SOT, RAIRD and LM cohorts, respectively. Participants had received three, four or ≥five vaccine doses at the time of testing in 28.5%, 61.8%, and 9.6%, respectively. In all groups, seropositivity was associated with younger age, higher number of vaccine doses and previous COVID-19 infection. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in SOT recipients receiving an anti-proliferative agent, calcineurin inhibitor and steroid concurrently, and those treated with anti-CD20 in the RAIRD and LM cohorts. Conclusions Approximately one in five individuals with SOT, RAIRD and LM have no detectable IgG spike-protein antibodies despite three or more vaccines, but this proportion reduces with sequential booster doses. Choice of immunosuppressant and disease-type is strongly associated with serological response. Antibody testing could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions. Trial registration Clinicaltrials.gov , NCT05148806