Severe acute myositis and myocarditis upon initiation of six-weekly Pembrolizumab post-COVID-19 mRNA vaccination

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within one month of receiving the initial cycle of the anti-PD-1 drug Pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Wellcome Intermediate Clinical Fellowship to BPF (no. 201488/Z/ 16/Z). RAW is funded by a Wellcome Trust Doctoral Training Fellowship (no. BST00070). The Oxford Radcliffe Biobank and Oxford Centre for Histopathology Research are supported by the University of Oxford, the Oxford CRUK Cancer Centre and the NIHR Oxford Biomedical Research Centre (Molecular Diagnostics Theme/Multimodal Pathology Subtheme), and the NIHR Cancer Research Network (CRN) Thames Valley network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Patients provided written informed consent for the donation of tissue and access to clinical records to the Oxford Radcliffe Biobank (ethical approval 19/SC/0173, projects 16/A019, 18/A064, and 19/A114). Ethics committee/IRB of University of Oxford (CUREC) gave ethical approval for this work (CUREC-1, R80630/RE001). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors