patient care perspectives

Impact of COVID-19 on Systemic Lupus Erythematosus

by George C. Tsokos, MD

Overview

Patients with systemic lupus erythematosus (SLE) may be more vulnerable to infections due to factors related to both the SLE and its treatment. Guidance has been issued on the use and timing of immunomodulatory therapies in relation to COVID-19 vaccine administration in patients with rheumatic and musculoskeletal diseases.

Expert Commentary

George C. Tsokos, MD

Professor of Medicine
Harvard Medical School
Chief, Division of Rheumatology and Clinical Immunology
Beth Israel Deaconess Medical Center
Boston, MA

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.”  

George C. Tsokos, MD

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+ CD38high 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.

References

ACR COVID-19 Vaccine Clinical Guidance Task Force. COVID-19 vaccine clinical guidance summary for patients with rheumatic and musculoskeletal diseases. Accessed May 21, 2021. https://www.rheumatology.org/Portals/0/Files/COVID-19-Vaccine-Clinical-Guidance-Rheumatic-Diseases-Summary.pdf

Calabrese LH, Winthrop K, Strand V, Yazdany J, Walter JE. Type I interferon, anti-interferon antibodies, and COVID-19. Lancet Rheumatol. 2021;3(4):e246-e247. doi:10.1016/S2665-9913(21)00034-5

Fernandez-Ruiz R, Paredes JL, Niewold TB. COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease. Transl Res. 2021;232:13-36. doi:10.1016/j.trsl.2020.12.007

Gupta S, Nakabo S, Chu J, Hasni S, Kaplan MJ. Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus. Preprint. medRxiv. 2020;2020.10.29.20222000. doi:10.1101/2020.10.29.20222000

Katsuyama E, Suarez-Fueyo A, Bradley SJ, et al. The CD38/NAD/SIRTUIN1/EZH2 axis mitigates cytotoxic CD8 T cell function and identifies patients with SLE prone to infections. Cell Rep. 2020;30(1):112-123.e4. doi:10.1016/j.celrep.2019.12.014

Lupus Foundation of America. Coronavirus (COVID-19) and lupus. Accessed May 21, 2021. https://www.lupus.org/resources/coronavirus-and-lupus#

Mason A, Rose E, Edwards CJ. Clinical management of lupus patients during the COVID-19 pandemic. Lupus. 2020;29(13):1661-1672. doi:10.1177/0961203320961848

Misra DP, Agarwal V, Gasparyan AY, Zimba O. Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets. Clin Rheumatol. 2020;39(7):2055-2062. doi:10.1007/s10067-020-05073-9

Ramirez GA, Gerosa M, Beretta L, et al; SMILE, Milan Lupus Consortium. COVID-19 in systemic lupus erythematosus: data from a survey on 417 patients. Semin Arthritis Rheum. 2020;50(5):1150-1157. doi:10.1016/j.semarthrit.2020.06.012

Tang W, Askanase AD, Khalili L, Merrill JT. SARS-CoV-2 vaccines in patients with SLE [published correction appears in Lupus Sci Med. 2021;8(1):e000479corr1]. Lupus Sci Med. 2021;8(1):e000479. doi:10.1136/lupus-2021-000479

Tsokos GC, Lo MS, Costa Reis P, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(12):716-730. doi:10.1038/nrrheum.2016.186

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