Circulating neutrophils from COVID-19 pneumonia patients demonstrate inflammasome activation and high nuclear citrullination. Plasma samples from healthy controls (n = 8) and patients with severe COVID-19 (n = 6) were evaluated for: (A) IL-1β, (B) IL-18, (C) H3cit, (D) dsDNA, and (E) MPO-DNA complexes. Values are means plus or minus SEM. Data were analyzed using Mann-Whitney U test; *P < .05, ***P < .0001. Neutrophils freshly isolated from healthy controls and patients with severe COVID-19 were stained with DAPI (blue) and (F) an anti-ASC antibody (red) or (I) with an anti-H3cit antibody (red). White arrows indicate the presence of the ASC speck. Nonspecific staining corresponds to immunostaining performed without primary antibodies. (F) Representative images from widefield microscopy of neutrophils. Scale bar, 10 μm. (G) Representative confocal microscopy images of an immunostained neutrophil and a PBMC from COVID-19 patient. Blue, DNA (DAPI); red, ASC antibody staining. Scale bar, 5 µm. (H) Quantification of neutrophils presenting a speck. (I) Representative images from widefield microscopy of neutrophils. Scale bar, 10 μm. (J) Quantification of neutrophils with nucleus positive for H3cit. Each dot represents 1 individual. Values are means plus or minus SEM. Data were analyzed by Mann-Whitney U test; *P < .005, **P < .001. (K) Correlation between the percentage of neutrophils positive for H3cit and percentage of neutrophils forming speck among all individuals healthy (▪) and COVID-19 patients (•). A nonparametric Spearman correlation test was computed. dsDNA, double-stranded DNA; H3cit, citrullinated histone H3; MPO-DNA, myeloperoxidase‐DNA; SEM, standard error of the mean.