Cardiovascular complication by COVID-19 infection in SSc patients with anti-RNA polymerase III antibody

OBJECTIVES: Autoantibodies represent a serological hallmark of SSc. Heart involvement in SSc patients includes diastolic dysfunction, conduction block, pericardial effusion, altered left ventricular ejection fraction (LVEF), valvular pathology, as well as myocardial inflammation and/or fibrosis. To characterize the role of anti-RNA polymerase III (RNAPIII) antibody positivity in the pathophysiology of coronavirus disease 2019 (COVID-19)-related cardiac involvement in SSc patients. METHODS: We retrospectively analysed four SSc patients with anti-RNAPIII antibodies who developed cardiac complications after COVID-19. This study was approved by the University of Osaka Clinical Research Review Board. RESULTS: All patients were female and had been diagnosed within the past 3 years. Case 1 presented with elevated myocardial enzymes and severe cardiac injury requiring mechanical circulatory support. The diagnosis of COVID-19-related fulminant myocarditis was made. The other three patients did not have elevated myocardial enzymes but had elevated brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) and pericardial effusion or decreased LVEF and respiratory distress, suggesting the appearance of COVID-19-induced cardiac dysfunction. CONCLUSION: Patients with anti-RNAPIII-positive SSc may have an increased risk of developing cardiac complications after COVID-19. The pathogenesis may involve angiotensin-converting enzyme 2 (ACE2)-mediated mechanisms, which may include reducing ACE2 expression, leading to increased angiotensin II activity and induce cytokine storm. These results underline the importance of understanding the interplay between autoimmune diseases and infections in promoting immune-mediated cardiac injury. Further investigation is needed to characterize the role of anti-RNAPIII antibodies in the pathophysiology of COVID-19-related cardiac involvement.