RNA-seq on CD16Int versus CD16High in severe COVID-19 patients
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that  causes a clinical disease called coronavirus disease 2019 (COVID-19). Approximately 20% of  infected patients experience a severe manifestation of the disease, causing bilateral pneumonia  and acute respiratory distress syndrome. Severe COVID-19 patients also have a pronounced  coagulopathy with approximately 30% of patients experiencing thromboembolic complications.  However, the cellular etiology driving the coagulopathy remains unknown. Here, we explore  whether the prominent neutrophilia seen in severe COVID-19 patients contributes to  inflammation-associated coagulation. We found in severe patients the emergence of a CD16Int  low-density inflammatory band (LDIB) neutrophil population that trends over time with changes  in disease status. These cells demonstrated spontaneous neutrophil extracellular trap (NET)  formation, higher phagocytic capacity, enhanced cytokine production, and associated clinically  with D-dimer, ferritin, and systemic IL-6 and TNF-a levels. Strikingly, LDIB neutrophils are the  major immune cells within the bronchoalveolar lavage (BAL) fluid with increased CXCR3 and  loss of CD44 and CD38 expression. We conclude that the LDIB subset contributes to COVID-  19-associated coagulopathy (CAC) and systemic inflammation and could be used as an adjunct  clinical marker to monitor disease status and progression. Identifying patients who are trending  towards LDIB crisis and implementing early, appropriate treatment could improve all-cause  mortality rates for severe COVID-19 patients. Overall design: Three paired CD16Int and CD16High samples from severe COVID-19 patients were compared with each other, as well as with three healthy donor NDN samples.