SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model

Serafini, R. A.; Frere, J. J.; Zimering, J.; Giosan, I. M.; Pryce, K. D.; Golynker, I.; Panis, M.; Ruiz, A.; tenOever, B.; Zachariou, V.

doi:10.1101/2022.08.19.504551

bioRxiv · 10.1101/2022.08.19.504551

SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model

Serafini, R. A.·Frere, J. J.·Zimering, J.·Giosan, I. M.·Pryce, K. D.·Golynker, I.·Panis, M.·Ruiz, A.·tenOever, B.·Zachariou, V.

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Abstract

Despite being largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and long-lasting phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster infection model to characterize the effects of SARS-CoV-2 versus Influenza A virus (IAV) infection on the sensory nervous system. Efforts to detect the presence of virus in the cervical/thoracic spinal cord and dorsal root ganglia (DRGs) demonstrated detectable levels of SARS-CoV-2 by quantitative PCR and RNAscope uniquely within the first 24 hours of infection. SARS-CoV-2-infected hamsters demonstrated mechanical hypersensitivity during acute infection; intriguingly, this hypersensitivity was milder, but prolonged when compared to IAV-infected hamsters. RNA sequencing (RNA-seq) of thoracic DRGs from acute infection revealed predominantly neuron-biased signaling perturbations in SARS-CoV-2-infected animals as opposed to type I interferon signaling in tissue derived from IAV-infected animals. RNA-seq of 31dpi thoracic DRGs from SARS-CoV-2-infected animals highlighted a uniquely neuropathic transcriptomic landscape, which was consistent with substantial SARS-CoV-2-specific mechanical hypersensitivity at 28dpi. Ontology analysis of 1, 4, and 30dpi RNA-seq revealed novel targets for pain management, such as ILF3. Meta-analysis of all SARS-CoV-2 RNA-seq timepoints against preclinical pain model datasets highlighted both conserved and unique pro-nociceptive gene expression changes following infection. Overall, this work elucidates novel transcriptomic signatures triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities while also highlighting several therapeutic targets for alleviation of infection-induced hypersensitivity. One Sentence SummarySARS-CoV-2 infection results in an interferon-associated transcriptional response in sensory tissues underlying time-dependent hypersensitivity.

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Serafini, R. A., Frere, J. J., Zimering, J., Giosan, I. M., Pryce, K. D., Golynker, I., Panis, M., Ruiz, A., tenOever, B., Zachariou, V.. 2022-08-19. SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model. https://doi.org/10.1101/2022.08.19.504551

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