Nonclassical monocyte disappearance and increased nigericin-triggered caspase-1 activation in nonclassical monocytes are associated with COVID-19 severity. Whole peripheral blood cells of healthy donors or COVID-19 patients were analyzed by flow cytometry using CD45, CD14, and CD16 markers. Whole peripheral blood was treated with vehicle (control) or nigericin (5 µM) for 30 minutes and monocyte subsets were analyzed for FAM-FLICA MFI (caspase-1 activation) (A,D,G) and nigericin-induced fold of FAM-FLICA MFI compared with control (B,E,H). Leukocytes were defined as CD45⁺ (C,F,I) and the frequency of monocyte subsets among leukocytes was analyzed: CD14^dimCD16⁺ nonclassical monocytes (C) CD14^highCD16⁻ classical monocytes (F) and CD14^highCD16⁺ intermediate monocytes (I). **P ≤ .01; ***P ≤ .001.