Neutrophil aggregates and active NETosis were prominent features in the lungs of COVID-19 patients.
Although neutrophil influx and NET release were reported in COVID-19 patients, their pathogenic role is yet to be understood. Massive neutrophil aggregates were found within the airways and alveolar spaces that displayed widespread alveolar architectural disintegration(Figure 5A-D) , The lung neutrophils displayed strong immunostaining for granule proteins including NE, MPO, and PAD4 co-localized within the regions of neutrophil aggregates in the alveoli(Figure 5E) . Accordingly, we measured an increase in total citrullinated proteins in COVID-19 lungs compared to non-COVID-19 lungs(Figure 5F) . Strong NE staining in the extracellular space within the disintegrated alveoli is consistent with the degranulation of neutrophils in the inflammatory microenvironment.