Researchers show impact of SARS-CoV-2 infection on somatoparesthesia in hamster model

In a recent article published in the journal scientific immunologyUnited States researchers conducted a longitudinal cohort study in a golden hamster model to find that the sensation induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection compared with influenza A virus (IAV) We investigated the change mechanism.

study: Predictors of long-term neutralizing antibody titers after COVID-19 vaccination with three vaccines: the BOOST studyImage Credit: Numstocker / Shutterstock

Background

Characterizing the molecular basis of the effects of SARS-CoV-2 infection on the sensory nervous system has implications for long-term coronavirus disease (COVID)-associated pain and other neurological problems such as neuropathy and myalgia. It may help develop new treatments. Long-term COVID, also known as acute sequelae of SARS-CoV-2, is the persistence of his COVID-19-like symptoms beyond 2 months after recovery and cannot be elucidated by alternative diagnoses.

Many mild and severe COVID-19 patients often experience sensory-related symptoms such as headaches, visceral pain, neuralgia, and rarely develop Guillain-Barré syndrome (GBS) and polyneuritis. These symptoms usually disappear after the infection clears in most people, but persist to subacute or chronic points in many others. However, few studies have investigated the mechanisms by which SARS-CoV-2 causes these abnormal somatosensory sensations.

About research

Dorsal root ganglia (DRGs) are sites of active viral replication and satellite-mediated sequestration. Therefore, in the present study, researchers investigated gene expression changes in spinal cord (SC) sensory tissue and DRG neck and thoracic regions after SARS-CoV-2 and IAV infection. After exposure, it was evaluated longitudinally. .

They collected these tissues at 1, 4, 7, and 14 days post-infection (dpi) in study groups infected with SARS-CoV-2 and IAV. Next, they used reverse transcription quantitative polymerase chain reaction (qPCR) to identify the presence of SARS-CoV-2 nucleocapsid (NC) protein transcripts and type I interferon (IFN-I)-stimulated Isg15 canonical transcripts. I rated it. Additionally, researchers used RNAscope in situ hybridization technology to determine whether SARS-CoV-2 transcripts localize to specific cell types in the DRG at 1 dpi.

The team also performed a monofilament test in IAV- or SARS-CoV-2-infected hamsters compared to mock-infected hamsters. , have helped delineate the effects of active and quiescent viral RNA and IFN-I responses on somatosensory. Additionally, the researchers performed transcriptional profiling and her Ingenuity Pathway Analysis (IPA) canonical pathway predictions on her RNA-seq data.

Investigation result

The authors found SARS-CoV-2 transcripts, but not their infectious agents, in the neck and thoracic SC sensory tissues and DRG of infected animals within the first 24 hours of intranasal infection. rice field. Compared with IAV-infected animals, SARS-CoV-2-infected hamsters exhibited mild but prolonged mechanical hypersensitivity.

RNA-sequencing analysis showed impaired type I IFN signaling in IAV-infected animals and 1–4 dpi perturbations in neuronal signaling in SARS-CoV-2-infected animals. Strikingly, the thoracic DRG of SARS-CoV-2-infected animals developed a neuropathic transcriptome 31 days after infection, consistent with SARS-CoV-2-specific mechanical hypersensitivity.

This data demonstrates and elucidates the transcriptomic signature of DRGs in SARS-CoV-2-infected hamsters that govern short- and long-term paresthesia. This appears to be a potential target for pain management, including the RNA-binding protein ILF3, previously validated in mouse pain models.

Although IAV-induced mechanical hypersensitivity completely subsided at 1 dpi, hypersensitivity due to SARS-CoV-2 infection declined gradually and the withdrawal threshold was reached significantly at 4 dpi, whereas IAV-induced hypersensitivity was more pronounced than hypersensitivity due to SARS-CoV-2. in the same period.

Differential gene expression analysis (GEA) of RNA-seq data revealed transcriptome changes in DRGs at different time points in SARS-CoV-2 and IAV-infected hamsters. SARS-CoV-2 infection caused more active differential gene expression at both time points: 344 and 63 genes at 1 and 4 dpi, respectively, whereas IAV infection resulted in 82 and 18 genes at 1 and 4 dpi, respectively. genes were differentially expressed. Perhaps SARS-CoV-2-induced transcriptional changes counteracted IFN-induced somatosensory sensitization by adopting a more active neuronal gene signature.

The pathways most enriched at 1 dpi in SARS-CoV-2-infected hamster tissues were axonal guidance and synaptogenic signaling and neuroinflammatory signaling at 4 dpi. For IAV-infected tissue samples, the top canonical pathways represent common viral response pathways. IPA analysis also showed neuron-specific transcriptional variations within the most upregulated canonical pathways based on genes with statistical significance of p<0.05.

Conclusion

This study established the relevance of the SARS-CoV-2 respiratory infection hamster model as a preclinical model of chronic pain and may aid in the evaluation of pharmacological treatments in the future. This model is consistent with acute and chronic somatosensory trajectories in many patients with COVID-19.

Furthermore, it has helped identify core mechanisms across pain models while providing insight into viral-mediated nociceptive states relevant to drug development.