Effectiveness of delayed second dose of AZD1222 vaccine in patients with autoimmune rheumatic disease

Abstract

There is paucity of data on extended dosing interval between two doses of AZD1222 (AstraZeneca) in patients with Autoimmune Rheumatic Diseases (AIRD). We aimed to study the humoral response and rate of breakthrough infections between the two groups who had received the second dose of vaccine at 4 weeks (Group 1) and 10–14 weeks (Group 2). From established cohort [COVID-19 vaccination cohort from CARE(CVCC)] of vaccinated patients with AIRD, those who had received AZD1222 were included and divided into two groups. Anti-Receptor Binding Domain (RBD) antibodies (IU/ml) were measured 1 month after the second dose. Its predictors and rate of breakthrough infections were studied. Four hundred ninety-five patients with AIRD were included in this study. Group 2 had higher anti-RBD antibody titres [1310.6 (±977.8) and [736 (±864.7), p = 0.0001. On univariate analysis, presence of Diabetes Mellitus; use of Methotrexate, Sulfasalazine, and Mycophenolate Mofetil; and vaccine interval were significantly associated with anti-RBD antibodies. Diabetes Mellitus and vaccine interval were independent predictors on multivariate analysis. Breakthrough infections were higher in Group 1 numerically on survival analysis but the difference was not significant (7.5% and 4.5%; log rank test: p = 0.25). In conclusion, increasing the gap between doses of the AZD1222 vaccine from 4 week to 10–14 weeks was found to be more beneficial in terms of antibody response in patients with AIRD. There was a trend towards higher breakthrough infections in the short interval group, supporting the antibody data. Key Points • There is paucity of data on effectiveness of increased dosing interval from 4-6 to 10-14 weeks for AZD1222 in patients with AIRDs • We observed a better humoral response with increased dosing interval with the interval and Diabetes Mellitus being independent predictors of the anti-RBD antibody levels • Breakthrough infections were numerically higher in the short interval group but the difference wasn't significant

B-Cell Responses to Sars-Cov-2 mRNA Vaccines

“…In another large retrospective study demonstrating enhanced protection from vaccination after prior infection, a prolonged interval between vaccine doses did not contribute to added protection in either uninfected or previously infected participants [76]. However, other, albeit smaller and less definitive studies have demonstrated increased protection with extended intervals [73,77], consistent with health-impact modeling [78], and changes in guidelines on dosing interval [79]. Several factors may contribute to differences in predicted or observed outcomes, including demographics, period of study, circulating variants, levels and sources of pre-existing immunity, as well as differences in vaccine efficacy [78,80].…”

Efficacy, Immunogenicity, and Safety of COVID-19 Vaccines in Patients with Autoimmune Diseases: A Systematic Review and Meta-Analysis

“…All studies concerned adult participants (the majority of participants were >18 years of age), and only one study also involved pediatric participants [91]. Sixty-six studies included participants who had only had a primary dose vaccine [8,29,30,[35][36][37][38][39]41,[82][83][84][85][86][87][88][89][90][91][92][93][97][98][99][100][101][102][103], whereas in ten studies participants had had a booster dose vaccine [31][32][33][34]40,42,81,[94][95][96].…”

“…Autoimmune medications given to the patients included alemtuzumab [29,34,48,66], abatacept [8,33,35,39,47,57,58,63,[72][73][74][75]94,98], anti-CD20/-B cell depleting therapy [8,29,[32][33][34][35]37,[39][40][41]43,45,[47][48][49][52][53][54][55]57,60,[62][63][64][65][66]72,74,75,87,89,92,94,[96]…”

Interplay of diabetes mellitus and rheumatic diseases amidst the COVID-19 pandemic: influence on the risk of infection, outcomes, and immune responses

“…Studies have also analyzed the effects of DM in RDs on the humoral immune response to SARS-CoV-2 vaccines [55][56][57]. A study in India reported a negative association between antispike antibody titers and DM in addition to a shorter dosing interval of 4 weeks between the two doses of AZD1222 (Aztra-Zenaca/ChAdOx1) vaccine in a cohort of 561 patients with RDs [54]. The presence of DM did not influence the response to BioNtech mRNA vaccine as reported in a study from Qatar in 100 patients with RDs [55].…”