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

Abstract

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.

Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms

“…In addition, autoantibodies to IL-1RA were also present in 62% (13/21) of samples of multisystem inflammatory syndrome in children (MIS-C), and further research is required to see if these have pathological effects [ 418 ]. Other studies awaiting peer-review notably observed significant increases in autoantibodies (n = 30) in severity to desmoglein 2 (DSG2), that can be present in heart, skin, or skeletal muscle [ 419 ]. The significance of autoantibody changes, presently, is largely unclear in research, and other authors concur that this could be a transient change but would need further research [ 420 ].…”

Desmoglein-2 and COVID-19 complications: insights into its role as a biomarker, pathogenesis and clinical implications

“…This raises the possibility that autoimmunity could contribute to the development of acute and chronic symptoms of COVID-19. DSG2 autoantibodies have the potential to be pathogenic and have been associated with ARVC and familial DCM [ (47,12]. In addition, the presence of DSG2 autoantibodies has been demonstrated to disrupt the normal functioning of DSG2 proteins, leading to interference with cell-to-cell adhesion [66,67].…”

“…Moreover, DSG2 and its autoantibody have both been implicated in the pathogenesis of many diseases especially those involving cardiac injury [66,103,104]. This recently includes COVID-19 [12,47].…”

“…Ward et al [12] recently associated increased levels of DSG2 proteins with severe cases of COVID-19, especially concerning cardiac injury. In COVID-19 patients who had died, they also detected DSG2 in the intercalated discs that connect cardiac muscle cells [12]. This further confirms the role of DSG2 in cardiac damage during COVID-19 infection.…”

“…A recent study has highlighted the potential role of DSG2 in the pathophysiology of COVID-19 [12]. SARS-CoV-2 has been shown to interact with DSG2, facilitating viral entry into cardiomyocytes and potentially contributing to myocardial injury [12]. Given the implications of cardiac involvement in severe COVID-19 cases, targeting DSG2 as a therapeutic intervention may hold promise.…”