We report a case of Type 1 Narcolepsy (NT1) following SARS-CoV-2 infection with undetectable cerebrospinal fluid (CSF) hypocretin-1 and HLA-DQB1*0602/*0301 haplotypes.  

NT1 is a rare neurologic disorder with severe hypersomnolence, cataplexy and REM instability. NT1 occurs with immune-mediated loss of hypocretin-producing neurons of the lateral hypothalamus and associated HLA DQB1*0602 haplotype. NT1 is associated with increased prevalence following H1N1, vaccination, and other autoimmune disease like multiple sclerosis. SARS-CoV-2 and NT1 are separately associated with olfactory dysfunction, the latter improved with intranasal orexin-A. The mechanistic postulation of SARS-CoV-2 triggered NT1 via the olfactory bulb predated this case. 

Multiple sleep latency test (MSLT): mean sleep latency 6.2 minutes, 5/5 sleep onset REM periods. PSG with PAP 5 cm H20: Total sleep time (TST) 8.9 hours, REM latency 7 minutes. Two-week actigraphy: average TST 8.3 hours. Heterozygous HLA-DQB1*0602/ *0301. CSF Orexin levels <50 pg/mL. Brain MRI was normal.

This is the first reported NT1 with close temporal relationship of SARS-CoV-2 infection demonstrating CSF orexin deficiency and high-risk HLA phenotypes. This case underscores the need for further understanding of (1) the mechanism and clinical spectrum of central hypersomnias, (2) genetic basis of autoimmunity in neurological disease, and (3) SARS-CoV-2-induced olfactory compromise as a model for CNS auto-neurodegeneration.