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Neuropilin‐1 as a Neuroinflammatory Entry Factor for SARS‐CoV‐2 Is Attenuated in Vaccinated COVID‐19 Patients: A Case–Control Study

Hosseini et al., Health Science Reports, doi:10.1002/hsr2.70630, Apr 2025
https://c19early.org/hosseini7.html
Case-control study of 80 COVID-19 patients and 30 healthy controls showing increased expression of Neuropilin-1 (NRP1) and IL-6 genes in COVID-19 patients, with higher expression correlating with disease severity. Vaccinated COVID-19 patients had significantly lower IL-6 expression compared to unvaccinated patients with moderate and severe disease, and reduced NRP1 expression compared to other patient groups. Authors suggest NRP1 and IL-6 may serve as biomarkers of disease severity and potential therapeutic targets due to their role in inflammation and cytokine storm.
Hosseini et al., 7 Apr 2025, Iran, peer-reviewed, 7 authors. Contact: azadmehr2010@gmail.com, a.azadmehr@mubabol.ac.ir.
Neuropilin‐1 as a Neuroinflammatory Entry Factor for SARS‐CoV‐2 Is Attenuated in Vaccinated COVID‐19 Patients: A Case–Control Study
Faezeh Hosseini, Abbas Azadmehr, Kiarash Saleki, Mohamadreza Ahmadifard, Morteza Oladnabi, Moein Shirzad, Mostafa Javanian
Health Science Reports, doi:10.1002/hsr2.70630
Background and Aim: COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as a pandemic infectious disease. So far, it has been known that this virus uses several receptors to enter the host cell, one of which is neuropilin-1 (NRP1). Also, one of the main causes of clinical manifestations, severity of disease, and mortality of patients is cytokine storm syndrome, one of these cytokines being interleukin (IL)-6. Our aim was to study the level of expression of NRP1 and IL-6 genes in COVID-19 patients by using peripheral blood mononuclear cells (PBMCs). Materials and Methods: Our study population included the test group (80 patients with COVID-19) and the control group (30 healthy individuals). Venous blood was taken from all subjects. After isolating PBMCs from blood using Ficoll, RNA was extracted. Then, cDNA synthesis, the expression level of NRP1 and IL-6 compared to GAPDH housekeeping gene was measured by real-time PCR. Results: The level of NRP1 gene expression was increased significantly in COVID-19 different groups compared to the control group. Surprisingly, it was observed that the amount of NRP1 gene decreased in the vaccinated group compared to nonvaccinated groups. IL-6 gene expression was also significantly increased in all groups except vaccinated patients compared to the control group. Also, the results indicated that there was a positive and statistically considerable relationship between IL-6 expression level and NRP1 expression level (p = 0.03). Conclusion: The significant increase in the expression of NRP1 and IL-6 genes in COVID-19 patients, especially in moderate and severe cases, indicates their potential involvement in the progression of the disease, which may serve as biomarkers of disease severity. Also, since these genes play an important role in causing severe inflammation, cytokine storm, and immunopathological complications of COVID-19, further investigations maybe needed to achieve therapeutic goals to control COVID-19 and similar diseases.
Author Contributions Faezeh Hosseini: conceptualization, investigation, writingoriginal draft, writingreview and editing, visualization, methodology, software, formal analysis, data curation. Abbas Azadmehr: visualization, methodology, supervision, resources, project administration, funding acquisition, writingreview and editing, data curation, conceptualization, investigation. Kiarash Saleki: investigation, methodology, visualization, writingreview and editing, software, formal analysis, data curation. Mohamadreza Ahmadifard: methodology, investigation, visualization. Morteza Oladnabi: investigation, visualization, methodology. Moein Shirzad: methodology. Mostafa Javanian: visualization, investigation. Ethics Statement This work was approved by Ethics Committee of Babol University of Medical Sciences, Babol, Iran (IR.MUBABOL.REC.1401.038). The patients/participants provided their written informed consent to participate in this study. Conflicts of Interest The authors declare no conflicts of interest.
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DOI record: { "DOI": "10.1002/hsr2.70630", "ISSN": [ "2398-8835", "2398-8835" ], "URL": "http://dx.doi.org/10.1002/hsr2.70630", "abstract": "<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background and Aim</jats:title><jats:p>COVID‐19 is caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) as a pandemic infectious disease. So far, it has been known that this virus uses several receptors to enter the host cell, one of which is neuropilin‐1 (NRP1). Also, one of the main causes of clinical manifestations, severity of disease, and mortality of patients is cytokine storm syndrome, one of these cytokines being interleukin (IL)‐6. Our aim was to study the level of expression of NRP1 and IL‐6 genes in COVID‐19 patients by using peripheral blood mononuclear cells (PBMCs).</jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p>Our study population included the test group (80 patients with COVID‐19) and the control group (30 healthy individuals). Venous blood was taken from all subjects. After isolating PBMCs from blood using Ficoll, RNA was extracted. Then, cDNA synthesis, the expression level of NRP1 and IL‐6 compared to GAPDH housekeeping gene was measured by real‐time PCR.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The level of NRP1 gene expression was increased significantly in COVID‐19 different groups compared to the control group. Surprisingly, it was observed that the amount of NRP1 gene decreased in the vaccinated group compared to nonvaccinated groups. IL‐6 gene expression was also significantly increased in all groups except vaccinated patients compared to the control group. Also, the results indicated that there was a positive and statistically considerable relationship between IL‐6 expression level and NRP1 expression level (<jats:italic>p</jats:italic> = 0.03).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The significant increase in the expression of NRP1 and IL‐6 genes in COVID‐19 patients, especially in moderate and severe cases, indicates their potential involvement in the progression of the disease, which may serve as biomarkers of disease severity. Also, since these genes play an important role in causing severe inflammation, cytokine storm, and immunopathological complications of COVID‐19, further investigations maybe needed to achieve therapeutic goals to control COVID‐19 and similar diseases.</jats:p></jats:sec>", "alternative-id": [ "10.1002/hsr2.70630" ], "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2024-10-19" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "2025-03-24" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 3, "value": "2025-04-07" } ], "author": [ { "affiliation": [ { "name": "Student Research Committee, Babol University of Medical Sciences Babol Iran" }, { "name": "Cellular and Molecular Biology Research Center Health Research 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