RT Journal Article SR Electronic T1 SARS-CoV-2 Infects Peripheral and Central Neurons of Mice Before Viremia, Facilitated by Neuropilin-1 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.05.20.492834 DO 10.1101/2022.05.20.492834 A1 Jonathan D. Joyce A1 Greyson A. Moore A1 Poorna Goswami A1 Emma H. Leslie A1 Christopher K. Thompson A1 Andrea S. Bertke YR 2022 UL http://biorxiv.org/content/early/2022/05/20/2022.05.20.492834.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.