Emergence and Compartmentalization of Fatal Multi-Drug-Resistant Cytomegalovirus Infection in a Patient With Autosomal-Recessive Severe Combined Immune Deficiency

Abstract

The authors describe a patient with autosomal-recessive severe combined immunodeficiency (SCID) with severe, multiorgan cytomegalovirus (CMV) disease. In the face of appropriate therapy, the patient developed a 100-fold gradient in viral load across the blood-brain barrier. Disseminated disease, including pneumonitis, contributed to a fatal outcome. Serial genotypic analyses revealed multiple UL97 and UL54 (DNA polymerase) mutations that conferred phenotypic resistance to all currently licensed systemic CMV antivirals.