Atypical hemolytic uremic syndrome induced by SARS-CoV2 infection in infants with EXOSC3 mutation

• Published in: Pediatric nephrology (Berlin, West) Vol. 37; no. 11; pp. 2781 - 2784
• Main Authors: Van Quekelberghe, Chantal, Latta, Kay, Kunzmann, Steffen, Grohmann, Maik, Hansen, Matthias
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2022; Springer Nature B.V
• Subjects: Atypical Hemolytic Uremic Syndrome - therapy; Brief Report; Complement activation; Complement system; Complement System Proteins; COVID-19; COVID-19 - complications; Endothelial cells; Exosome Multienzyme Ribonuclease Complex - genetics; Genetic disorders; Hemolytic uremic syndrome; Humans; Hypoplasia; Infant; Infants; Infections; Kidneys; Medicine; Medicine & Public Health; Microvasculature; Mutation; Nephrology; Neurodegenerative diseases; Neurodegenerative Diseases - complications; Patients; Pediatrics; Ribonucleic acid; RNA; RNA processing; RNA, Viral; RNA-Binding Proteins - genetics; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Thrombotic Microangiopathies - complications; Thrombotic Microangiopathies - genetics; Thrombotic microangiopathy; Urology; COVID-19; aHUS; RNA exosome; mutation; EXOSC3 mutation
• ISSN: 0931-041X; 1432-198X; 1432-198X
• DOI: 10.1007/s00467-022-05566-6

Background Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by systemic thrombotic microangiopathy mainly in the kidneys and mostly due to genetic disorders leading to uncontrolled activation of the complement system. Severe complications of SARS-CoV2 infection are linked to microvascular injury and complement activation is suspected to play a role in the pathogenesis of endothelial cell damage in severe COVID-19. Methods We present the first two cases of aHUS triggered by SARS-CoV-2 infection in two unrelated infants with the same mutation in the RNA exosome gene EXOSC3 . This mutation is known to cause pontocerebellar hypoplasia type 1b, an autosomal-recessive neurodegenerative disease. So far, no kidney involvement in affected persons was reported. Results As eculizumab treatment was unsuccessful and complement-mediated disorders were ruled out, we suppose that the atypical HUS in our two patients is not due to complement-mediated thrombotic microangiopathy but rather due to a dysfunction of the RNA exosome. Conclusions The RNA exosome is crucial for the precise processing and degradation of nuclear and cytoplasmatic RNA. We suspect that the SARS-CoV-2 infection led to changes in RNA that could not be offset by the defective RNA exosome in our two patients. The accumulation/wrong processing of the viral RNA must have led to the endothelial cell damage resulting in aHUS. This would be a new — “RNA-induced” — mechanism of aHUS.