Objective: To evaluate B-cell- and T-cell-mediated immune response to SARS-CoV-2 mRNA vaccination in patients with complex or rare systemic autoimmune diseases previously been treated with or under continuous treatment with B-cell-targeted therapies including rituximab (RTX) and belimumab (BEL). Materials and methods: Twenty-eight consecutive patients receiving RTX (n = 11) or BEL (n = 17) treatment and 13 age-/sex-matched controls (non-rheumatic healthcare personnel) were recruited. None of the patients had detectable anti-SARS-CoV-2 antibodies caused by prior exposure to the virus. All the patients and controls received mRNA vaccines and were tested three to four weeks after completion of vaccination. In all the RTX patients, vaccination was started within 5 months from the last infusion, and B-cell depletion was confirmed in all but one of them. Total anti-SARS-CoV-2 RBD antibodies were analyzed using a diagnostic assay, while T-cell response was evaluated using the interferon-gamma release assay (IGRA). Further, SARS-CoV-2 pseudoviruses were employed to verify the strain-specific neutralizing capacity of the antibodies. Results: Detectable anti-SARS-CoV-2 antibodies were documented in 1 out of the 11 RTX patients and 16 of the 17 BEL patients. The median concentration in the RTX and BEL patients was significantly lower than that in the controls (39.6 AU/ml vs. 1133 AU/ml, p = 0.002). The result of IGRA was positive in 8 of the 11 (72.7%) RTX patients and 16 of the 17 (94.1%) BEL patients, and interferon release in both the RTX and BEL patients was comparable to that in the control participants. Conclusion: B-cell-targeted therapies do not preclude SARS-CoV-2 vaccination, since virus-specific cellular immunity can be induced even in the absence of circulating B cells. An important finding was that lupus patients treated with BEL developed immune responses to SARS-CoV-2; this indicates retention of the immunogenicity of the COVID-19 vaccine.
