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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]; pInterpretation: Our data suggest that seroconversion after a first COVID-19 vaccination is delayed in older patients on specific immunosuppressive drugs, but that second or repeated exposure to SARS-CoV-2, either via infection or vaccination, improves humoral immunity in patients treated with immunosuppressive drugs. Therefore, delayed second dosing of COVID-19 vaccines should be avoided in patients receiving immunosuppressive drugs. Future studies that include younger patients need to be done to confirm the generalisability of our results.FUNDING: ZonMw, Reade Foundation, and MS Center Amsterdam.

OBJECTIVE: The objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies (DMTs) in relation to timing of vaccination and B-cell count.METHODS: OCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70.RESULTS: 87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL).CONCLUSIONS: Low B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.

Introduction: Data on immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases are still scarce, because these patients were largely excluded from SARS-CoV-2 vaccine trials. Methods: Serum samples of patients with autoimmune diseases (n = 480) and healthy controls (n = 204) included in two ongoing prospective cohort studies were collected after first or second SARS-CoV-2 vaccinations. Seroconversion rates and IgG antibody titers against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were measured. Multivariable logistic and linear regression analyses were used to investigate associations between medication, seroconversion rates and IgG antibody titers respectively. Findings: Seroconversion rates after a first SARS-CoV-2 vaccination in 111 patients on methotrexate (25%, adjusted OR: 0.1, 95% CI: 0.1 – 0.2, P < 0.001) and 15 patients on anti-CD20 therapies (0%, P < 0.001) were lower compared to 103 healthy controls (71%). For patients on tumor necrosis factor (TNF) inhibitors (adjusted OR: 0.7, 95% CI: 0.4 – 1.4, P = 0.20) and patients on prednisone monotherapy (adjusted OR: 0.6, 95% CI: 0.2 – 1.5, P = 0.25) seroconversion rates were similar compared to controls. After the second SARS-CoV-2 vaccination seroconversion rates exceeded 88% in all patient subgroups, except in patients treated with anti-CD20 therapies (2 (33%) of 6). Seroconversion rates and IgG antibody titers were similar for patients with a prior SARS-CoV-2 infection who had received a single vaccine dose and patients without a prior SARS-CoV-2 who had received two vaccine doses. Interpretation: Treatment regimens other than anti-CD20 therapies of patients with autoimmune diseases do not need to be postponed when these patients receive a SARS-CoV-2 vaccination. Patients receiving anti-CD20 therapies may benefit from a second booster vaccination, as our data suggest that repeated exposure to SARS-CoV-2 vaccines or the virus itself enhances the development of humoral immunity in these patients. Funding: ZonMw, Reade Foundation and MS Center Amsterdam. Declaration of Interest: None to declare. Ethical Approval: The research protocols were approved by the medical ethical committee of the VU University medical center (registration number 2020.169 and 2020.370). All participants gave informed consent.