# Beyond prediction: unveiling the prognostic power of μ-opioid and cannabinoid receptors, alongside immune mediators, in assessing the severity of SARS-CoV-2 infection

**Authors:** Masoumeh Tavakoli-Yaraki, Aida Abbasi, Fatemeh Nejat Pishkenari, Saeed Baranipour, Alireza Jahangirifard, Seyed Bashir Mirtajani, Zahra Noorani Mejareh, Mohammad Amin Vaezi, Jila Yavarian, Bahare Abdollahi, Talat Mokhtari-Azad, Vahid Salimi

PMC · DOI: 10.1186/s12879-024-09280-6 · BMC Infectious Diseases · 2024-04-12

## TL;DR

This study identifies key receptors and immune markers that predict the severity of SARS-CoV-2 infection and suggest their roles in disease progression.

## Contribution

The study introduces novel predictive markers combining opioid and cannabinoid receptors with immune mediators for SARS-CoV-2 severity assessment.

## Key findings

- MOR and CB2 gene expression is elevated in severe SARS-CoV-2 cases.
- MCP-1, IL-17, IFN-γ, and osteopontin levels correlate with disease severity.
- CB2 expression is significantly linked to other mediators like MOR and IFN-γ.

## Abstract

This study aims to explore the potential of utilizing the expression levels of cannabinoid receptor 2 (CB2), μ-opioid receptor (MOR), MCP-1, IL-17, IFN-γ, and osteopontin as predictors for the severity of SARS-CoV-2 infection. The overarching goal is to delineate the pathogenic mechanisms associated with SARS-CoV-2.

Using quantitative Real-time PCR, we analyzed the gene expression levels of CB2 and MOR in nasopharynx specimens obtained from patients diagnosed with SARS-CoV-2 infection, with 46 individuals classified as having severe symptoms and 46 as non-severe. Additionally, we measured the circulating levels of MCP-1, IL-17, IFN-γ, and osteopontin using an ELISA assay. We examined the predictive capabilities of these variables and explored their correlations across all patient groups.

Our results demonstrated a significant increase in MOR gene expression in the epithelium of patients with severe infection. The expression of CB2 receptor was also elevated in both male and female patients with severe symptoms. Furthermore, we observed concurrent rises in MCP-1, IL-17, IFN-γ, and osteopontin levels in patients, which were linked to disease severity. CB2, MOR, MCP-1, IL-17, IFN-γ, and osteopontin showed strong predictive abilities in distinguishing between patients with varying degrees of SARS-CoV-2 severity. Moreover, we identified a significant correlation between CB2 expression and the levels of MOR, MCP-1, osteopontin, and IFN-γ.

These results underline the interconnected nature of molecular mediators in a sequential manner, suggesting that their overexpression may play a role in the development of SARS-CoV-2 infections.

## Linked entities

- **Genes:** CNR2 (cannabinoid receptor 2) [NCBI Gene 1269], OPRM1 (opioid receptor mu 1) [NCBI Gene 4988]
- **Proteins:** CCL2 (C-C motif chemokine ligand 2), IL17A (interleukin 17A), IFNG (interferon gamma)

## Full-text entities

- **Genes:** SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, OPRM1 (opioid receptor mu 1) [NCBI Gene 4988] {aka LMOR, M-OR-1, MOP, MOR, MOR1, OPRM}, CNR2 (cannabinoid receptor 2) [NCBI Gene 1269] {aka CB-2, CB2, CX5}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}
- **Diseases:** infection (MESH:D007239), SARS-CoV-2 (MESH:D000086382)
- **Species:** Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC11015610/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11015610/full.md

## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC11015610/full.md

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Source: https://tomesphere.com/paper/PMC11015610