Antibody development after COVID-19 vaccination in patients with autoimmune diseases in the Netherlands: a substudy of data from two prospective cohort studies

Abstract

Background Data are scarce on immunogenicity of COVID-19 vaccines in patients with autoimmune diseases, who are often treated with immunosuppressive drugs. We aimed to investigate the effect of different immunosuppressive drugs on antibody development after COVID-19 vaccination in patients with autoimmune diseases. Methods In this study, we used serum samples collected from patients with autoimmune diseases and healthy controls who were included in two ongoing prospective cohort studies in the Netherlands. Participants were eligible for inclusion in this substudy if they had been vaccinated with any COVID-19 vaccine via the Dutch national vaccine programme, which at the time was prioritising vaccination of older individuals. Samples were collected after the first or second COVID-19 vaccination. No serial samples were collected. Seroconversion rates and IgG antibody titres against the receptor-binding domain of the SARS-CoV-2 spike protein were measured. Logistic and linear regression analyses were used to investigate the association between medication use at the time of vaccination and at least until sampling, seroconversion rates, and IgG antibody titres. The studies from which data were collected are registered on the Netherlands Trial Register, Trial ID NL8513, and ClinicalTrials.org, NCT04498286. Findings Between April 26, 2020, and March 1, 2021, 3682 patients with rheumatic diseases, 546 patients with multiple sclerosis, and 1147 healthy controls were recruited to participate in the two prospective cohort studies. Samples were collected from patients with autoimmune diseases (n=632) and healthy controls (n=289) after their first (507 patients and 239 controls) or second (125 patients and 50 controls) COVID-19 vaccination. The mean age of both patients and controls was 63 years (SD 11), and 423 (67%) of 632 patients with autoimmune diseases and 195 (67%) of 289 controls were female. Among participants without previous SARS-CoV-2 infection, seroconversion after first vaccination were significantly lower in patients than in controls (210 [49%] of 432 patients vs 154 [73%] of 210 controls; adjusted odds ratio 0·33 [95% CI 0·23–0·48]; p<0·0001), mainly due to lower seroconversion in patients treated with methotrexate or anti-CD20 therapies. After the second vaccination, seroconversion exceeded 80% in all patient treatment subgroups, except among those treated with anti-CD20 therapies (three [43%] of seven patients). We observed no difference in seroconversion and IgG antibody titres between patients with a previous SARS-CoV-2 infection who had received a single vaccine dose (72 [96%] of 75 patients, median IgG titre 127 AU/mL [IQR 27–300]) and patients without a previous SARS-CoV-2 infection who had received two vaccine doses (97 [92%] of 106 patients, median IgG titre 49 AU/mL [17–134]). Interpretation Our data suggest that seroconversion after a first COVID-19 vaccination is delay...

Humoral and cellular immunogenicity to a second dose of COVID-19 vaccine BNT162b2 in people receiving methotrexate or targeted immunosuppression: a longitudinal cohort study

“… 23 Although not statistically significant, the data from our limited sample size also suggest numerically lower levels of anti-spike IgG in immunosuppressed patients, compared with controls. Similar trends were identified in other cohorts of patients with immune-mediated inflammatory diseases, 9 , 19 , 24 and these findings have raised questions about whether dose modification of methotrexate or temporary discontinuation could enhance immune responses to COVID-19 vaccines. As this strategy was shown to be successful in promoting immunogenicity to the influenza vaccine, 25 a 2 week interruption in methotrexate after the COVID-19 booster is currently under investigation in a multicentre, randomised controlled trial.…”

The Use of COVID-19 Vaccines in Patients with SLE

“…Izmirly et al showed that fully vaccinated SLE patients (n=90) produced significantly lower IgG antibodies against SARS-CoV-2 spike receptor binding domain (RBD) than healthy controls (HCs) (n=20) [14]. Boekel et al reported that among participants without previous SARS-CoV-2 infection, seroconversion rates after first COVID-19 vaccination in patients with AIIRDs (n=432) were lower than HCs (n=210), an effect that was mainly driven by those treated with MTX or B cell-depletion therapies; however, differences in seroconversion rates were similar across autoimmune disease types examined [15]. Similarly, Ammitzbøll et al observed a higher seroconversion rate following BNT162b2 vaccine in SLE (n=73) than RA (n=64) patients, but the difference was not statistically significant after adjusting for RTX treatment [16].…”

Preserved T cell responses to SARS-CoV-2 in anti-CD20 treated multiple sclerosis

“…[1][2][3][4][5][6] Indeed, serum levels of SARS-CoV-2 immunoglobulin (Ig)G following SARS-CoV-2 vaccinations and infections are reduced in anti-CD20 treated pwMS. [7][8][9] Nevertheless, in addition to antibody levels, protection from infection, and especially from severe courses of coronavirus disease-19 (COVID- 19), may depend on neutralizing capacity and avidity of anti-SARS-CoV-2 antibodies as well as on induction of SARS-CoV-2 specific T cells. [10][11][12] However, data on anti-SARS-CoV-2 antibody neutralization capacity and avidity in anti-CD20 treated pwMS are scarce.…”