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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. We find raised levels of anti-DSG2 autoantibodies in sera from individuals following severe COVID-19. Staining of post-mortem cardiac tissue from individuals that died from COVID-19 with an anti-DSG2 antibody 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. [ABSTRACT FROM AUTHOR]

Antineuronal antibodies are associated with rare paraneoplastic neurological syndromes, and their identification alerts clinicians to examine for the presence of a tumor. Presented here is laboratory experience (prevalence, difficulties, and procedures) and several interesting but inconclusive results. A total of 1045 samples were screened over a 2-year period; 91 showed a degree of binding of antibodies to the cerebellum, and 22 of these 91 were confirmed, by Western blot, to have specific antineuronal antibodies. Thirteen of 22 were Hu-positive, and 6 of these also had antinuclear antibodies. Six were Yo-positive, 2 had anti-Ma antibodies, and 1 was Tr-positive. An additional 27 of 91 patients had cerebellar antibodies giving recognized staining patterns (Hu, Yo, and Ma). However, Western blot did not confirm these specificities, and hence they were reported as atypical. Six of 27 of these patients had neoplasms; 3 of the 6 gave nucleolar patterns (not Ma). Two appeared similar to Yo, and 1 similar to Hu. Antineuronal antibodies are rare, and in the absence of a specific etiology patients should be examined further for the possible presence of an underlying tumor. Methodical classification of the antibodies must be conducted to avoid incorrect reporting. Further criteria on the typing/ reporting of atypical results may aid diagnosis of paraneoplastic neurological syndromes. [ABSTRACT FROM AUTHOR]