COVID-19 as a possible risk factor for poor prognosis in systemic sclerosis

Abstract

Introduction. Scleroderma Renal Crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc), traditionally associated with anti-RNA polymerase III antibodies, corticosteroid use, and diffuse skin involvement. However, the role of COVID-19 as a potential trigger for SRC remains poorly understood. This study explores the occurrence of COVID-19-associated SRC, focusing on its clinical presentation, underlying risk factors, and outcomes.

Case presentation. We present a case series of two unvaccinated patients with systemic sclerosis who developed SRC following COVID-19 infection, despite the absence of traditional risk factors. Clinical features, laboratory findings, renal histopathology, and disease progression were analyzed to assess potential mechanisms linking SARS-CoV-2 infection to SRC onset. Both patients developed abrupt-onset malignant hypertension and acute kidney injury after supporting the COVID-19. Neither patient had a history of corticosteroid use or known anti-RNA polymerase III positivity, suggesting an alternative mechanism of SRC activation. Notably, both cases had pre-existing renal anomalies (renal developmental abnormality and prior nephrectomy), which may have contributed to increased susceptibility. Despite aggressive management, both patients developed dialysis-dependent renal failure and succumbed to SRC-related complications.

Conclusions. Our findings highlight COVID-19 as a potential trigger for SRC, possibly through endothelial dysfunction, inflammatory cytokine storms, and renal microangiopathy. The presence of pre-existing kidney conditions may further predispose SSc patients to SRC following SARS-CoV-2 infection. Additionally, the lack of vaccination in these cases raises the question of whether COVID-19 immunization could reduce SRC risk. Further research is needed to elucidate the pathophysiology, risk stratification, and long-term outcomes of COVID-19-associated SRC, as well as the role of vaccination in prevention.