Key result
Severe COVID-19 is linked to ~3-fold higher anti-desmoglein 2 autoantibody levels versus healthy controls.
Why the study?
Post-acute cardiac sequelae are recognized complications of COVID-19, and prior evidence showed persistent autoantibodies consistent with targeting desmosomal proteins, which maintain structural integrity of tissues.
Does SARS-CoV-2 infection increase the production of anti-desmoglein 2 autoantibodies and contribute to cardiac intercalated disc disruption?
Observational (n=252)
Yes
Does SARS-CoV-2 infection increase the production of anti-desmoglein 2 autoantibodies and contribute to cardiac intercalated disc disruption?
Severe COVID-19 is associated with elevated anti-DSG2 autoantibodies and structural changes at cardiac intercalated discs, proposing a potential autoimmune mechanism for post-acute cardiac complications.
Post-acute cardiac sequelae, following SARS-CoV-2 infection, are well recognized 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 analyzed 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-19 patients. Furthermore, we find that DSG2 autoantibody levels are increased significantly in convalescent sera following severe COVID-19 but not in hospitalized 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 confirmed DSG2 protein within the intercalated discs and disruption of the intercalated disc between cardiomyocytes in patients who died from COVID-19. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection.
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Ward et al. (2023) conducted an observational in COVID-19 (n=252). SARS-CoV-2 infection vs. Healthy controls and non-COVID illness was evaluated on Anti-desmoglein 2 (DSG2) autoantibody levels (p=<0.0001). Severe SARS-CoV-2 infection was associated with significantly elevated anti-desmoglein 2 autoantibody levels in both acute (median OD 0.90) and convalescent (median OD 1.10) phases compared to healthy controls (median OD 0.35, p<0.0001).
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