SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection

Post-acute cardiac sequelae, following SARS-CoV-2 infection, are well recognised as complications of COVID-19. We have previously shown the persistence of autoantibodies against antigens in skin, muscle, and heart in individuals following severe COVID-19; the most common staining on skin tissue displayed an inter-cellular cement pattern consistent with antibodies against desmosomal proteins. Desmosomes play a critical role in maintaining the structural integrity of tissues. For this reason, we analysed desmosomal protein levels and the presence of anti-desmoglein (DSG) 1, 2 and 3 antibodies in acute and convalescent sera from patients with COVID 19 of differing clinical severity. We find increased levels of DSG2 protein in sera from acute COVID patients. Furthermore, we find that DSG2 autoantibody levels are increased significantly in convalescent sera following severe COVID-19 but not in hospitalised patients recovering from influenza infection or healthy controls. Levels of autoantibody in sera from patients with severe COVID-19 were comparable to levels in patients with non-COVID-19-associated cardiac disease, potentially identifying DSG2 autoantibodies as a novel biomarker for cardiac damage. To determine if there was any association between severe COVID-19 and DSG2, we stained post-mortem cardiac tissue from patients who died from COVID-19 infection. This revealed disruption of the intercalated disc between cardiomyocytes that was consistent with separation of the DSG2 protein homodimer. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection. ### Competing Interest Statement Mark T. Drayson owns stock in Abingdon Health, outside the submitted work. All other authors declare no competing interests. ### Funding Statement The authors would like to acknowledge the staff of the University of Birmingham Clinical Immunology Service for facilitating laboratory studies. The convalescent health care worker study (COCO) was carried out at the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. This study was funded as part of the UK Coronavirus Immunology Consortium funded by NIHR and UKRI. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. Post-mortems were performed by Dr Esther Youd, Royal Glamorgan Hospital, Cwm Taf University Health Board and Dr Gareth Leopold, Morriston Hospital, Swansea Bay University Health Board. Post-mortem sample collection was funded by an MRC Clinical Research Training Fellowship and the Welsh Assembly Government. ### 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: Northwest-Preston Research Committee (ref: 20/NW/0240 IRAS Project ID: 282164) gave approval for the recruitment of 39 individuals in ITU with severe COVID-19 and 25 individuals in convalescence from admission to the ITU with severe COVID-19 infection. London-Camden and Kings Cross Research Ethics Committee (ref. 20/HRA/1817) gave approval for recruitment of individuals as part of the COvid-19 COnvalescent immunity (COCO) study. Outer West London Research Ethics Committee (ref: 09/MRE00/67) and the NHS National Research Ethics Service (ref: 09/H0709/52) gave approval for the influenza samples. Birmingham and Black Country atrial fibrillation registry (BBC-AF, IRAS ID 97753, REC reference 12/WM/0344) gave approval for the samples comprising the cardiac cohort. The NHS National Research Ethics Committee (ref: 19/NE/0336, IRAS ID 193937) gave approval for the post-mortem samples as part of the Long and Short-Term effects of Standard-of-Care treatments for Cancer (LoST-SoCC) study. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced are available upon request to the authors.