LAUSR

Although largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and chronic phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster model to characterize and compare the effects of infection with SARS-CoV-2 and influenza A virus (IAV) on the sensory nervous system. We detected SARS-CoV-2 transcripts but no infectious material in the cervical and thoracic spinal cord and dorsal root ganglia (DRGs) within the first 24 hours of intranasal virus infection. SARS-CoV-2–infected hamsters exhibited mechanical hypersensitivity that was milder but prolonged compared with that observed in IAV-infected hamsters. RNA sequencing analysis of thoracic DRGs 1 to 4 days after infection suggested perturbations in predominantly neuronal signaling in SARS-CoV-2–infected animals as opposed to type I interferon signaling in IAV-infected animals. Later, 31 days after infection, a neuropathic transcriptome emerged in thoracic DRGs from SARS-CoV-2–infected animals, which coincided with SARS-CoV-2–specific mechanical hypersensitivity. These data revealed potential targets for pain management, including the RNA binding protein ILF3, which was validated in murine pain models. This work elucidates transcriptomic signatures in the DRGs triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities. Description Long Covid pain may arise from a targetable antiviral response to SARS-CoV-2 particles in dorsal root ganglia. The pain of long COVID Some people infected with SARS-CoV-2, the virus that causes COVID-19, experience a range of symptoms after the resolution of infection, such as neurological issues that include generalized pain, neuropathy, and myalgia. Serafini et al. found that non-infectious viral RNA was detectable in the dorsal root ganglia of hamsters after intranasal infection with SARS-CoV-2. This phenomenon was associated with a durable gene expression signature in sensory neurons that partly resembled those of mouse models of inflammatory and injury-induced neuropathic pain but was distinct from those in mice infected with influenza virus. The findings further identify the cytokine-associated factor ILF3 and other potential therapeutic targets to treat pain associated with long COVID and other neuropathies. –LKF