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Antibody Development after SARS-CoV-2 Vaccinations in Elderly Patients with Autoimmune Diseases: Data From a Prospective Controlled Cohort Study

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.