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

10.1101/2022.07.26.22278002

MedRxiv

Contributing to research themes:

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

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.

Author list:

Affiliations:

  1. Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
  2. Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
  3. Institute of Cancer and Genomic Sciences, University of Birmingham, United Kingdom
  4. Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom
  5. Department of Critical Care, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
  6. National Heart and Lung Institute, Imperial College London, London, UK
  7. Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
  8. Department of Clinical Immunology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United

Authors:

KingdomKerensa E Ward1, Lora Steadman1, Abid R Karim1, Gary M Reynolds1, Matthew Pugh3, Winnie Chua4, Sian E Faustini1, Tonny Veenith5, Ryan S Thwaites6, Peter JM Openshaw6, Mark T Drayson1, Adrian M Shields1,8, Adam F Cunningham7, David C. Wraith1, Alex G Richter1,8