Patients with autoimmune rheumatic disease have been identified as a vulnerable population at risk for severe COVID-19 illness. Some of this vulnerability may be related to treatment. Patients with SLE who receive long-term treatment with steroids, mycophenolate mofetil, or cyclophosphamide may have compromised cytotoxic responses that could impact their infection risk.

Other risks may be related to the immune dysfunction of SLE. Epidemiologically, it does not appear that SLE increases one’s susceptibility to COVID-19 after infection with SARS-CoV-2; however, there is a conceptual basis for exercising more caution in this population. T-cell cytotoxic responses are decreased in patients with SLE, and there is evidence that high levels of CD8+ CD38^high lymphocytes in the peripheral blood of patients with SLE may be linked to infections. Those with SLE also produce more proinflammatory cytokines, including interleukin 17, which suggests a preexisting inflammation that may be exaggerated by COVID-19. Stimulation of the adaptive immune system after SARS-CoV-2 infection might predispose patients with SLE to more severe outcomes. 

Another consideration in this patient population is the complex relationship between type I interferon (IFN) and SLE. Gupta and colleagues reported an increased prevalence of preexisting anti-IFNα autoantibodies in patients with both SLE and COVID-19 compared with the reported prevalence in those with SLE and in the general population with severe COVID-19. To further complicate matters, the SARS-CoV-2 virus itself encodes a protein that blocks IFN, acting as a decoy IFN receptor. 

The American College of Rheumatology has issued guidance on COVID-19 vaccination for patients with SLE and other autoimmune inflammatory and rheumatic diseases. To date, there is no preference for one mRNA-based vaccine over the other. There are a few points to consider in trying to optimize a patient’s response to the vaccine. As expected, those on high-dose steroids may have a decreased response. The timing of vaccine administration relative to SLE therapy administration is also a consideration. Patients on B-cell depletion therapy, such as those taking rituximab, should receive the vaccine before their next scheduled dose of rituximab. While there are still unanswered questions regarding COVID-19 vaccination in SLE, the anticipated benefits of vaccination in this patient population are significant. Organizations such as the American College of Rheumatology and the Lupus Foundation of America continue to help patients navigate the changing terrain.