Severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain-1 and transferrin receptor

Background: High serum ferritin (hyperferritinemia) is a routine finding in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a reliable marker of coronavirus disease 2019 severity. We previously observed hypomethylation of the ferritin heavy chain-1 (FTH1) g...

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Main Authors: Mohammad G. Mohammad, Nada Mazen Farhat, Ameera Abu-Qiyas, Jasmin Shafarin, Bilal Rah, Nour Dallal, Wassim El Baba, Fatima Bukhalaf, Ameera Askari, Mohamad Madkhour, Jibran Sualeh Muhammad, Mawieh Hamad
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-07-01
Series:Advances in Biomedical and Health Sciences
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Online Access:https://journals.lww.com/10.4103/abhs.abhs_115_24
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author Mohammad G. Mohammad
Nada Mazen Farhat
Ameera Abu-Qiyas
Jasmin Shafarin
Bilal Rah
Nour Dallal
Wassim El Baba
Fatima Bukhalaf
Ameera Askari
Mohamad Madkhour
Jibran Sualeh Muhammad
Mawieh Hamad
author_facet Mohammad G. Mohammad
Nada Mazen Farhat
Ameera Abu-Qiyas
Jasmin Shafarin
Bilal Rah
Nour Dallal
Wassim El Baba
Fatima Bukhalaf
Ameera Askari
Mohamad Madkhour
Jibran Sualeh Muhammad
Mawieh Hamad
author_sort Mohammad G. Mohammad
collection DOAJ
description Background: High serum ferritin (hyperferritinemia) is a routine finding in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a reliable marker of coronavirus disease 2019 severity. We previously observed hypomethylation of the ferritin heavy chain-1 (FTH1) gene induced by the SARS-CoV-2 spike protein. Given that this protein is present in the majority of SARS-CoV-2 vaccines, the question of whether such vaccines can induce epigenetic changes and alter the pattern of FTH1 expression to induce hyperferritinemia is yet to be explored. Methods: Blood samples from 84 healthy individuals who received one or more jabs of Sinopharm and/or Pfizer vaccines or were not vaccinated were assessed for plasma ferritin levels and the expression of FTH1 and transferrin receptor (TFRC) genes. The expression of ten-eleven translocation (TETs 1–3) methylcytosine dioxygenases that facilitate cytosine demethylation and DNA methyltransferases (DNMTs 1, 3A and 3B), which mediate cytosine methylation was also examined. Results: Our results showed that plasma ferritin levels in vaccinated individuals were slightly, but not significantly, higher than those in unvaccinated controls. However, the expression of FTH1 and TFRC genes was significantly upregulated in vaccinated individuals compared to that in controls. Moreover, the expression of TETs 1-3 and DNMTs 1, 3A, and 3B was significantly higher in the vaccinated individuals than in the controls. Conclusion: These findings suggest that SARS-CoV-2 vaccination is associated with significant epigenetic reprogramming that upregulates FTH1 and TFRC expression without precipitating hyperferritinemia. This indicates that individuals vaccinated against SARS-CoV-2 have minimal or no risk of chronic inflammation or tissue damage related to hyperferritinemia.
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spelling doaj-art-c4b0c2dadc6f44888046e65340e8f2e12025-08-20T03:39:15ZengWolters Kluwer Medknow PublicationsAdvances in Biomedical and Health Sciences2773-15452773-15532025-07-014313314010.4103/abhs.abhs_115_24Severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain-1 and transferrin receptorMohammad G. MohammadNada Mazen FarhatAmeera Abu-QiyasJasmin ShafarinBilal RahNour DallalWassim El BabaFatima BukhalafAmeera AskariMohamad MadkhourJibran Sualeh MuhammadMawieh HamadBackground: High serum ferritin (hyperferritinemia) is a routine finding in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a reliable marker of coronavirus disease 2019 severity. We previously observed hypomethylation of the ferritin heavy chain-1 (FTH1) gene induced by the SARS-CoV-2 spike protein. Given that this protein is present in the majority of SARS-CoV-2 vaccines, the question of whether such vaccines can induce epigenetic changes and alter the pattern of FTH1 expression to induce hyperferritinemia is yet to be explored. Methods: Blood samples from 84 healthy individuals who received one or more jabs of Sinopharm and/or Pfizer vaccines or were not vaccinated were assessed for plasma ferritin levels and the expression of FTH1 and transferrin receptor (TFRC) genes. The expression of ten-eleven translocation (TETs 1–3) methylcytosine dioxygenases that facilitate cytosine demethylation and DNA methyltransferases (DNMTs 1, 3A and 3B), which mediate cytosine methylation was also examined. Results: Our results showed that plasma ferritin levels in vaccinated individuals were slightly, but not significantly, higher than those in unvaccinated controls. However, the expression of FTH1 and TFRC genes was significantly upregulated in vaccinated individuals compared to that in controls. Moreover, the expression of TETs 1-3 and DNMTs 1, 3A, and 3B was significantly higher in the vaccinated individuals than in the controls. Conclusion: These findings suggest that SARS-CoV-2 vaccination is associated with significant epigenetic reprogramming that upregulates FTH1 and TFRC expression without precipitating hyperferritinemia. This indicates that individuals vaccinated against SARS-CoV-2 have minimal or no risk of chronic inflammation or tissue damage related to hyperferritinemia.https://journals.lww.com/10.4103/abhs.abhs_115_24ferritin heavy chain-1hyperferritinemiamethylationsevere acute respiratory syndrome coronavirus 2vaccine
spellingShingle Mohammad G. Mohammad
Nada Mazen Farhat
Ameera Abu-Qiyas
Jasmin Shafarin
Bilal Rah
Nour Dallal
Wassim El Baba
Fatima Bukhalaf
Ameera Askari
Mohamad Madkhour
Jibran Sualeh Muhammad
Mawieh Hamad
Severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain-1 and transferrin receptor
Advances in Biomedical and Health Sciences
ferritin heavy chain-1
hyperferritinemia
methylation
severe acute respiratory syndrome coronavirus 2
vaccine
title Severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain-1 and transferrin receptor
title_full Severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain-1 and transferrin receptor
title_fullStr Severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain-1 and transferrin receptor
title_full_unstemmed Severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain-1 and transferrin receptor
title_short Severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain-1 and transferrin receptor
title_sort severe acute respiratory syndrome coronavirus 2 vaccination associates with upregulated expression of ferritin heavy chain 1 and transferrin receptor
topic ferritin heavy chain-1
hyperferritinemia
methylation
severe acute respiratory syndrome coronavirus 2
vaccine
url https://journals.lww.com/10.4103/abhs.abhs_115_24
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