NETs associate with microthrombi formation and platelet deposition in COVID-19 patients. (A) We stained for NETs and platelets using immunofluorescence in COVID-19 lung tissue obtained from autopsy cases #1 and #3. Early-stage NET-forming neutrophils (MPO, white) express citrullinated histone H3 (green). Microthrombi stained for early-stage NET-forming neutrophils and platelets (PF4; red). DAPI served as a nuclear DNA counterstain (blue). Scale bars, 100 μm (low-magnification, 2 leftmost images). For case #3, higher-magnification images are presented along with single-channel images. Scale bars, 20 μm. Yellow arrows point to thrombi with early-stage NET-forming neutrophils. Colocalized PF4 and early stage NET-forming neutrophils were not present in the analyzed lung sample from case #2. (B) We used flow cytometry to quantify platelet-neutrophil aggregates in whole blood from COVID-19 patients (n = 5) and healthy donors (n = 6). We used ELISA to quantify plasma levels of D-dimer (C), VWF antigen (D), PF4 (E), and RANTES (F) in available plasma from 18 to 22 COVID-19 patients and 5 to 7 healthy donors. Student t test (B), Mann-Whitney or Student t test, depending on the normality of distribution (C-F).