Considering that the heterodimer of p65 iso5 with either p50 or p65 amplify the transcriptional activity of IL-6 and TNF-α promoters and the p65 iso5 mRNA levels are higher in COVID-19 subjects, p65 iso5 may be involved in the onset of cytokine storm and development of severe symptoms in patients with COVID-19. This evidence concerns the gene RELA and COVID-19.