In a patient cohort of 30 patients with mild and severe COVID-19, we observed a significant upregulation of CD74 surface expression on CD4+ and CD8+ T cells in patients with severe (WHO grade ≥ 5) compared to patients with only mild disease (WHO grade 1–3), which was accompanied by CD74 upregulation on classical monocytes. The gene discussed is CD74; the disease is COVID-19.