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Brief communication Lupus Sci Med: first published as 10.1136/lupus-2021-000479 on 8 March 2021. Downloaded from SARS- CoV-2 vaccines in patients with SLE Wei Tang ,1 Anca D Askanase ,1 Leila Khalili ,1 Joan T Merrill2 To cite: Tang W, Askanase AD, ABSTRACT Khalili L, et al. SARS- CoV-2 As the Moderna (mRNA-1273) and Pfizer/BioNTech Key messages vaccines in patients with SLE. (BNT162b2) vaccines become available to patients with What is already known about this subject? Lupus Science & Medicine autoimmune diseases and SLE, practitioners will have 2021;8:e000479. doi:10.1136/ There have been previous studies on patients with to inform them about the safety and efficacy of these ► lupus-2021-000479 SLE and COVID-19, and patients with SLE and vac- vaccines. Here we discuss the challenges of applying cines; however, there is minimal information about vaccine data to patients with autoimmune diseases and patients with lupus and SARS- CoV-2 vaccinations. Received 15 January 2021 the evidence available in the literature that may help in the Revised 11 February 2021 decision process. What does this study add? Accepted 20 February 2021 ► This paper discusses the challenges of applying vac- cine data to patients with autoimmune diseases and The COVID-19 pandemic has affected nearly reviews the evidence available in the literature. every corner of the world and changed the How might this impact clinical practice or future face of medicine. Almost a year into the developments? pandemic, there have been over 91 million ► This paper may help practitioners counsel patients cases and more than 1 970 000 deaths glob- with autoimmune diseases who are eligible for ally.1 During the winter of 2021, there has vaccination. been a new surge of virulent strains in many parts of the world with no assurances of when uncontrolled autoimmunity appear to be lasting relief can be expected. Given these present in those most ill from COVID-19.14–16 grim statistics, the approval and initial disper- Patients with SLE in our cohort experi- sion of the Moderna and Pfizer/BioNTech enced COVID-19 infections at a rate similar vaccines are monumental events. There is to that of the general population (27/450 http://lupus.bmj.com/ limited knowledge about the safety and effi- or 6%), and 6/27 (22.2%) experienced a cacy of the COVID-19 vaccines in patients with disease flare within 22 days after developing SLE. While the overall safety and efficacy of symptoms.17 Of these six flares, five were the vaccines are reassuring, reports of immu- mild/moderate and one was severe, using nological adverse reactions to the vaccine may SLE Disease Activity Index Flare Index defi- be concerning to people with autoimmune nitions. The symptoms manifested included diseases such as SLE. arthritis, alopecia, rash, pleurisy and serolog- on September 29, 2021 by guest. Protected copyright. SLE is characterised by dysregulation in ical worsening (low complement components 2 3 type I interferon pathways. Type I inter- C3/C4 and antibodies to double- stranded © Author(s) (or their ferons are key components of the innate and DNA (anti- dsDNA)). Although these observa- employer(s)) 2021. Re- use adaptive immune responses to new patho- tions did not seem to indicate a high risk of permitted under CC BY- NC. No gens.4 The critical role of type I interferons commercial re- use. See rights serious flares, further long- term longitudinal and permissions. Published by in antiviral immunity is well known, including studies are needed to determine the impact 5 6 BMJ. responses to SARS-CoV-2. While data are of COVID-19 infection on SLE disease activity. 1Rheumatology, Columbia limited, patients with SLE do not seem to be Both Moderna (mRNA-1273) and Pfizer/ University Irving Medical Center, at higher risk of SARS- CoV-2 infections or BioNTech (BNT162b2) vaccines contain New York, New York, USA severe COVID-19 disease compared with the 2 RNA that encodes the stabilised prefusion Arthritis and Clinical general population.7–9 However, patients with Immunology Program, SARS- CoV-2 Spike (S) protein. The RNA Oklahoma Medical Research SLE may be at higher risk of hospitalisation enters host cells and produces non-virulent 10 11 Foundation Arthritis and Clinical during the COVID-19 disease course. In Spike protein that elicits high titres of neutral- Immunology Research Program, addition, it is possible that COVID-19 leads to ising antibodies and robust antigen- specific Oklahoma City, Oklahoma, USA increased SLE disease activity.12 13 COVID-19 CD8+ and Th1- type CD4+ T- cell responses.18–21 Correspondence to has been associated with the development of The immunogenic protein includes the full- Dr Anca D Askanase; ada20@ autoantibodies in the serum of hospitalised length S protein, with both the receptor- cumc. columbia. edu patients and features suggestive of severe, binding subunit (S1) and the membrane Tang W, et al. Lupus Science & Medicine 2021;8:e000479. doi:10.1136/lupus-2021-000479 1 Lupus Science & Medicine Lupus Sci Med: first published as 10.1136/lupus-2021-000479 on 8 March 2021. Downloaded from fusion subunit (S2). These are the first mRNA-based underlying pathological immune variables and degree of antiviral vaccines in human use and, as such, produced immune suppression. some public controversy. Phase I trials found systemic There are a number of factors at play that may provide side effects in up to 90% of participants.18 19 However, unique challenges to the response of patients with lupus the late phase vaccine trials provided reassurance about to SARS- CoV-2 vaccines. Quantitative and qualitative their safety prior to what is planned to be the largest-scale lymphocyte defects are prevalent in SLE. Lymphopenia worldwide vaccine distribution in history.22 23 is one of the most common haematological manifesta- The efficacy rate in preventing COVID-19 infections tions in SLE,26 resulting from a combination of lympho- for the Moderna (mRNA-1273) and Pfizer/BioNTech cytotoxic antibodies, complement- mediated cytolysis, (BNT162b2) vaccines was 94.1% and 95.0%, respec- impaired lymphopoiesis, and side effects of immunosup- tively. The phase III trials of both vaccines reported pressants and B-cell depleting agents.27 28 In addition, low percentages of serious adverse events (below CD8+ T- cell responses are dampened in patients with 0.1%).22 23 Local reactions were common and included SLE, and the compromised cytotoxicity results in suscep- tenderness, erythema and swelling at injection sites. tibility to viral infections.29–32 Furthermore, decreased Transient systemic reactogenicity such as fever, fatigue, immunogenicity and inadequate immune responses have headache, and muscle and joint pain were noted. These been reported in patients with SLE receiving vaccines effects are generally seen within 24–48 hours following against pneumococcus and influenza.33–35 Any condition the vaccination and one or more may occur in up to 95% that shortens durability of responses that build immunity of vaccine recipients.22 23 Earlier work from Pfizer/BioN- or impairs immunological memory might weaken the Tech on a vaccine (BNT162b1) that encodes the secreted long- term efficacy of vaccinations in patients with SLE. trimerised SARS- CoV-2 receptor–binding domain was Some clinical evidence supports this theory. Serial anti- abandoned because of greater severity of systemic reac- body titers to capsular polysaccharides were followed up tions in older adults.18 24 for 3 years in 19 patients with SLE after immunisation Unfortunately, patients treated with immunosuppres- with polyvalent pneumococcal polysaccharide vaccine; sants or immune- modifying drugs for >14 days within 6 at year 3, the antibody levels of vaccinated patients with months of entry were excluded from all phases of Moderna SLE dropped below the threshold of protection in 8 of 19 (mRNA-1273) vaccine trials (NCT04470427).19 23 In the (42%) patients, and 1 patient developed a pneumococcal Pfizer/BioNTech (BNT162b2) vaccine trials, individ- pneumonia.36 Taken together, these data illustrate that uals with a history of autoimmune disease or an active much remains to be learnt about vaccine responses in autoimmune disease requiring therapeutic intervention SLE. In the setting of dysregulated cellular and humoral were specifically excluded from phase I (NCT04368728), immunity, patients with SLE might require modifications and patients who received treatment with immunosup- in vaccination strategies to achieve adequate and durable pressive therapy, including cytotoxic agents or systemic immune responses. http://lupus.bmj.com/ corticosteroids, were excluded from phases I–III.22 24 The Previous studies have established that similar type I applicability of the published data to the safety and effi- interferon and proinflammatory cytokine pathways are cacy of COVID-19 RNA vaccines in patients with autoim- shared between SLE and COVID-19,2 3 5 6 which could mune disorders is unknown, especially in those patients either potentiate or dysregulate immune responses to receiving immunosuppressive treatment. SARS- CoV-2 vaccines while triggering disease activity in The dysregulation of the immune systems and concur- previously stable lupus. Vaccine- associated enhanced rent use of immunosuppressive therapies raise theoretical respiratory disease was not observed in either the Moderna on September 29, 2021 by guest. Protected copyright. concerns about the efficacy of vaccinations in patients (mRNA-1273) or Pfizer/BioNTech (BNT162b2) vaccines with SLE. To the extent
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