A Large Cluster of New Onset Autoimmune Myositis in the Yorkshire Region Following SARS-CoV-2 Vaccination

Abstract

Background: The novel SARS-CoV-2 vaccines partially exploit intrinsic DNA or RNA adjuvanticity, with dysregulation in the metabolism of both these nucleic acids independently linked to triggering experimental autoimmune diseases, including lupus and myositis.

Methods: Herein, we present 15 new onset autoimmune myositis temporally associated with SARS-CoV-2 RNA or DNA-based vaccines that occurred between February 2021 and April 2022. Musculoskeletal, pulmonary, cutaneous and cardiac manifestations, laboratory and imaging data were collected.

Results: In total, 15 cases of new onset myositis (11 polymyositis/necrotizing/overlap myositis; 4 dermatomyositis) were identified in the Yorkshire region of approximately 5.6 million people, between February 2021 and April 2022 (10 females/5 men; mean age was 66.1 years; range 37-83). New onset disease occurred after first vaccination (5 cases), second vaccination (7 cases) or after the third dose (3 cases), which was often a different vaccine. Of the cases, 6 had systemic complications including skin (3 cases), lung (3 cases), heart (2 cases) and 10/15 had myositis associated autoantibodies. All but 1 case had good therapy responses. Adverse event following immunization (AEFI) could not be explained based on the underlying disease/co-morbidities.

Conclusion: Compared with our usual regional Rheumatology clinical experience, a surprisingly large number of new onset myositis cases presented during the period of observation. Given that antigen release inevitably follows muscle injury and given the role of nucleic acid adjuvanticity in autoimmunity and muscle disease, further longitudinal studies are required to explore potential links between novel coronavirus vaccines and myositis in comparison with more traditional vaccine methods.

Keywords: COVID vaccination; adjuvanticity; myositis.

Figure 1

Map highlighting the distribution of new-onset myositis cases across the Yorkshire region, adapted from https://d-maps.com/carte.php?num_car=18610&lang=en (accessed on 12 May 2022). Dewsbury and District Hospital is part of The Mid Yorkshire Hospitals NHS Trust, alongside Pinderfiels Hospital of Wakefield.

Figure 2

Chest X-ray (A) and high-resolution computed tomography scan (B,C) of case 3 (female, 58 years old) with findings compatible with interstitial lung disease. Lung biopsy not performed.

Figure 3

Panel (A)—MRI scan of thighs from Case 1 (female, 68 years old). Oedema in the quadriceps (vastus intermedium femuri; vasti medialis and rectum femuri) bilaterally, pointing to inflammation in the muscle masses explored. Panel (B)—Muscle biopsy from case 10 (female, 71 years old). Haematoxylin/Eosin, magnification 400×. Perimyseal pathology with local thrombosis consistent with a vasculopathy and macrophages present consistent with immune-mediated necrotising myositis. Anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies were positive.

Figure 4

Panel (A): Conventional vaccines involve the delivery of a killed pathogen, attenuated pathogen or a protein subunit with adjuvants—including alum and others—to the inoculation site. This is associated with local muscle and endothelial and supporting tissue injury at the site of vaccination. It is thought that uptake of both the antigens and adjuvants by the antigen presenting cells leads to activation of such cells and migration to the regional lymph nodes where lymphocyte priming takes place and robust antibody responses to antigen takes place. In theory, vaccine-associated injury from the injecting needle might release self-antigens that are also taken up by the Antigen-Presenting Cells (APCs) and could theoretically lead to tolerance failure and autoimmunity. However, this is not something that is recognised in the clinical setting with conventional vaccines; hence, it seems unlikely to occur. Panel (B): Conventional vaccines the novel DNA- and RNA-based vaccines are also taken up by antigen-presenting cells and migrate to regional lymph nodes and likewise damaged self-muscle, endothelial and stromal tissue elements from sites of injury could undergo pinocytosis and likewise be transported. Copying elements of the viral life cycle within APCs facilitates CD4 and cytotoxic CD8 T-cell responses, that are superior to conventional vaccines and could thus contribute also to the development of better cell-mediated immune responses [28,29]. There is actually a very limited amount of data about the uptake and processing of nucleic acid vaccines following intramuscular injection; however, direct uptake of RNA and DNA into the muscle has been reported [26,30,31]. Further experimental studies and epidemiological surveys are needed to test this hypothesis. Image created with BioRender.com.