Human Coronavirus OC43 Associated with Fatal Encephalitis.

To the Editor: Encephalitis is a serious neurologic syndrome characterized by brain inflammation that may be fatal. Although the majority of cases are caused by viruses, the identification of a causal organism can be difficult. Encephalopathy that affects patients with immunodeficiency is particularly challenging to diagnose, since the clinical presentation may be atypical and the differential diagnosis may include unusual pathogens or a noninfective cause. Deep sequencing of clinical samples has the potential to identify the pathogens associated with encephalitis, particularly in cases in which traditional techniques have not identified the candidate causative pathogen.1 Here we report the use of deep sequencing of a brain biopsy sample obtained from an 11-monthold boy with severe combined immunodeficiency who had symptoms of viral encephalitis with negative results on conventional diagnostic polymerase-chain-reaction (PCR) assay. The boy’s family provided written informed consent. The boy underwent unconditioned cord-blood transplantation, which resulted in T-cell engraftment. Nonetheless, his condition continued to deteriorate, and he died 1.5 months after receiving the transplant. RNA sequencing of a brain biopsy sample obtained 2 months after the onset of symptoms showed the presence of human coronavirus OC43 (HCoV-OC43), which was sub-