Chronic Aichi Virus Infection As a Cause of Long-Lasting Multiorgan Involvement in Patients With Primary Immune Deficiencies.

This article focuses on the identification and characterization of chronic Aichi virus (AiV) infection in patients with primary immune deficiencies (PIDs) presenting with immunodysregulation-related multiorgan disease. Using metagenomic next-generation sequencing (mNGS), AiV was detected in tissue biopsies or bodily fluids of six male PID patients exhibiting symptoms such as chronic hepatitis, splenomegaly, nephritis, and CD8+ T-cell infiltration, while no AiV was found in asymptomatic immunodeficient controls. In situ hybridization confirmed AiV RNA presence in hepatocytes and spleen tissue, and viral clearance following hematopoietic stem cell transplantation correlated with clinical improvement, supporting a causal role of AiV in these immunopathological conditions. The study highlights the diagnostic challenges of AiV infection due to low and intermittent viral loads and underscores the importance of restoring B-cell immunity for viral clearance and symptom resolution.