ABSTRACT
Neurological symptoms are increasingly associated with COVID-19, suggesting that SARS-CoV-2 is neuroinvasive. Although studies have focused on neuroinvasion through infection of olfactory neurons and supporting cells or hematogenous spread, little attention has been paid to the susceptibility of the peripheral nervous system to infection or to alternative routes of neural invasion. We show that neurons in the central and peripheral nervous systems are susceptible to productive infection with SARS-CoV-2. Infection of K18-hACE2 mice, wild-type mice, and primary neuronal cultures demonstrates viral RNA, protein, and infectious virus in peripheral nervous system neurons, spinal cord, specific brain regions, and satellite glial cells. Moreover, we found that SARS-CoV-2 infects neurons at least in part via neuropilin-1. Our data show that SARS-CoV-2 rapidly invades and establishes productive infection in previously unassessed sites in the nervous system via direct invasion of neurons before viremia, which may underlie some cognitive and sensory symptoms associated with COVID-19.