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 ) 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.