Systematic review of spontaneous reports of myocarditis and pericarditis in transplant recipients and immunocompromised patients following COVID-19 mRNA vaccination

Figure 1. Tree diagram detailing the characteristics of vaccinees submitting spontaneous reports of myocarditis and pericarditis to EudraVigilance for European Union and European Economic Area only, following COVID-19 messenger RNA (mRNA) vaccines in immunocompromised individuals. Reports of myocarditis or pericarditis were searched in the EudraVigilance database following COVID-19 mRNA vaccines, either Moderna (Spikevax) or Pfizer/BioNTech (Comirnaty) (n=50 reports). The resultant reports were further assessed for individuals that were likely to be immunosuppressed based on the following search terms (transplant medications*, HIV/AIDS treatments, EU-approved cancer therapies). Concomitant medications were used as a proxy for disease status. *Counts are not mutually exclusive; one report may contain multiple concomitant medications from different categories. †Where tacrolimus, mycophenolate mofetil, ciclosporin or prednisolone were reported as concomitant medications. ‡Methotrexate was included as a potential transplant medication, however due to its wide use in autoimmune disease this was listed independently of the treatments used as a proxy for transplantation.

Figure 2. Tree diagram detailing the characteristics of spontaneous reports of myocarditis and pericarditis on the Vaccine Adverse Event Reporting System (VAERS) database following COVID-19 messenger RNA (mRNA) vaccines in immunocompromised individuals. Reports of myocarditis, pericarditis or myopericarditis were searched in the VAERS database following COVID-19 mRNA vaccines, either Moderna or Pfizer BioNTech. The resultant reports were further assessed for individuals that were likely to be immunocompromised based on the following search terms (transplant, tacrolimus, mycophenolate mofetil, methotrexate, prednisolone, ciclosporin). Transplant recipients were assessed separately to immunocompromised individuals that received medication, independent of disease setting. *Unspecified category, †cancer defined by use of cancer-approved medicines.

Figure 3. Tree diagram detailing the characteristics of spontaneous reports of myocarditis and pericarditis on the Yellow Card database following COVID-19 messenger RNA (mRNA) vaccines in immunocompromised individuals (Yellow Card, UK). Reports of myocarditis, pericarditis or myopericarditis from immunocompromised individuals were searched in the Yellow Card scheme following COVID-19 mRNA vaccines, either Moderna or Pfizer BioNTech. Data provided by Medicines and Healthcare products Regulatory Agency, datalock 1 December 2021. *n=3 unspecified, †n=2 under 18 years. For age category n=5 unknown.

Figure 4. Schematic of the immune response to antigen. Antigen is part of a foreign/non-self pathogen and is presented by an antigen-presenting cell (APC) either following viral protein digestion and presentation on the major histocompatibility complex (MHC) or via messenger RNA (mRNA) translation of the protein within the APC then the protein is presented on the MHC. The non-self protein presented on the MHC is recognised by B and T cells. This triggers a cascade of intracellular signalling responses and leads to the maturation of the B cells, within the germinal centre of a lymph node. The germinal centre reaction involves interactions with B cells, antigen and T cells; leading to somatic hypermutation of the B cell receptor (BCR), generating a BCR that is better adapted to recognise the antigen. The B cell then differentiates into memory B cells and plasma B cells to release the antibodies into the general circulation to clear the body of the infection.