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The overarching goal is to delineate the pathogenic mechanisms associated with SARS-CoV-2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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-\u03b3, and osteopontin using an ELISA assay. We examined the predictive capabilities of these variables and explored their correlations across all patient groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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-\u03b3, and osteopontin levels in patients, which were linked to disease severity. CB2, MOR, MCP-1, IL-17, IFN-\u03b3, 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-\u03b3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Graphical Abstract<\/jats:title><\/jats:sec>","DOI":"10.1186\/s12879-024-09280-6","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T15:01:59Z","timestamp":1712934119000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond prediction: unveiling the prognostic power of \u03bc-opioid and cannabinoid receptors, alongside immune mediators, in assessing the severity of SARS-CoV-2 infection"],"prefix":"10.1186","volume":"24","author":[{"given":"Masoumeh","family":"Tavakoli-Yaraki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida","family":"Abbasi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh Nejat","family":"Pishkenari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeed","family":"Baranipour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alireza","family":"Jahangirifard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Bashir","family":"Mirtajani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra Noorani","family":"Mejareh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Amin","family":"Vaezi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jila","family":"Yavarian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahare","family":"Abdollahi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talat","family":"Mokhtari-Azad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-7846","authenticated-orcid":false,"given":"Vahid","family":"Salimi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"issue":"1","key":"9280_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s12929-022-00872-5","volume":"29","author":"AC Borczuk","year":"2022","unstructured":"Borczuk AC, Yantiss RK. 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