Accumulating data suggest that treatment with anti-CD20 therapy, such as rituximab and ocrelizumab, puts patients at considerably increased risk of developing severe outcomes from COVID-19 (risk ratios ranging from 1·7 to 5·5 have been reported).This reported risk emphasizes how important it is that these patients develop protective immunity via COVID-19 vaccinations, but, unfortunately, studies have shown that humoral immune responses after COVID-19 vaccination are poor in patients with rheumatic diseases or multiple sclerosis who are taking anti-CD20 agents, even after two doses.Therefore, it is highly relevant to investigate the effects of a third COVID-19 vaccine dose in patients receiving rituximab and critically discuss the place of rituximab in treatment strategies for patients with rheumatic diseases.All patients were treated with rituximab, and concomitant treatment with conventional synthetic disease-modifying antirheumatic drugs was paused 1 wk before until 2 wk after each vaccination.Classification of antibody respose (no response, weak response, and response) was based on immunoglobulinG antibody levels found in healthy controls.Only patients with a weak or absent antibody response after two vaccine doses received a third dose (n=49); healthy controls did not receive a third dose.Cellular analyses to evaluate CD4+ and CD8+ T-cell responses were done in a subset of randomly chosen participants (19 patients and 20 healthy controls after the second vaccine dose, and 12 patients after the third vaccine dose).A third dose only marginally improved seroconversion rates; 29 (59·2%) of 49 patients had no response and 12 (24·5%) had a weak antibody response.By contrast, T-cell responses after two vaccine doses were similar for patients and controls, and a third vaccine dose slightly increased SARS-CoV-2-specific CD4+and CD8+ T-cell counts.Altogether, Jyssum and colleagues8 showed that the effects of a third dose of COVID-19 vaccine on humoral and cellular immunity in patients with rheumatoid arthritis receiving rituximab are marginal and therefore unlikely to considerably improve humoral protection against severe COVID-19.Physicians always need to carefully weigh the benefits against the risks before prescribing immunosuppressive treatment, and normally this balance is in favor of benefit due to low absolute risk of becoming infected with a dangerous pathogen.During the COVID-19 pandemic, however, people are constantly at a substantial risk of becoming infected with SARS-CoV-2, which means that the risks of rituximab treatment become considerably more important.Because of this altered risk-benefit evaluation, it could be argued that physicians should discuss the necessity of rituximab with their patients, and, when possible, prescribe other treatments.In addition to implications for treatment strategies regarding rituximab itself, the data from Jyssum and colleagues also have important implications for therapeutic strategies when patients receiving rituximab become infected with SARS-CoV-2.Data from the RECOVERY trial9 show that therapeutic monoclonal SARS-CoV-2 antibody infusions significantly reduced mortality in patients with severe COVID-19 who had no detectable SARS-CoV-2 antibodies before infection.In conclusion, the current literature suggests that treatment with rituximab during the ongoing COVID-19 pandemic puts patients at an increased risk of COVID-19-related hospitalisation and death, even after vaccination.Because the results from Jyssum and colleagues indicate that a third COVID-19 vaccination does not substantially improve humoral protection, physicians should discuss alternative therapies with patients who receive or would start treatment with rituximab, at least for the remainder of the COVID-19 pandemic.In addition, patients receiving rituximab should be actively advised to contact a physician as soon as they test pos. for COVID-19, so that early treatment with monoclonal SARS-CoV-2 antibodies and antiviral therapy can be considered.