TY - JOUR
T1 - Circulating Markers of Neutrophil Extracellular Traps Are of Prognostic Value in Patients With COVID-19
AU - Ng, Henry
AU - Havervall, Sebastian
AU - Rosell, Axel
AU - Aguilera, Katherina
AU - Parv, Kristel
AU - von Meijenfeldt, Fien A
AU - Lisman, Ton
AU - Mackman, Nigel
AU - Thalin, Charlotte
AU - Phillipson, Mia
PY - 2020/12/3
Y1 - 2020/12/3
N2 - OBJECTIVE: The full spectrum of coronavirus disease 2019 (COVID-19) infection ranges from asymptomatic to acute respiratory distress syndrome, characterized by hyperinflammation and thrombotic microangiopathy. The pathogenic mechanisms are poorly understood, but emerging evidence suggest that excessive neutrophil extracellular trap (NET) formation plays a key role in COVID-19 disease progression. Here, we evaluate if circulating markers of NETs are associated with COVID-19 disease severity and clinical outcome, as well as to markers of inflammation and in vivo coagulation and fibrinolysis. Approach and Results: One hundred six patients with COVID-19 with moderate to severe disease were enrolled shortly after hospital admission and followed for 4 months. Acute and convalescent plasma samples as well as plasma samples from 30 healthy individuals were assessed for markers of NET formation: citrullinated histone H3, cell-free DNA, NE (neutrophil elastase). We found that plasma levels of NET markers were all elevated in patients with COVID-19 relative to healthy controls, were associated with respiratory support requirement and short-term mortality, and declined to those found in healthy individuals 4 months post-infection. Levels of the NET markers also correlated with white blood cells, neutrophils, inflammatory cytokines, and C-reactive protein, as well as to markers of in vivo coagulation, fibrinolysis, and endothelial damage.CONCLUSIONS: Our findings suggest a role of NETs in COVID-19 disease progression, implicating their contribution to an immunothrombotic state. Further, we observed an association between circulating markers of NET formation and clinical outcome, demonstrating a potential role of NET markers in clinical decision-making, as well as for NETs as targets for novel therapeutic interventions in COVID-19.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04402944, NCT04541979, NCT04445285, NCT04432987, NCT04402970.
AB - OBJECTIVE: The full spectrum of coronavirus disease 2019 (COVID-19) infection ranges from asymptomatic to acute respiratory distress syndrome, characterized by hyperinflammation and thrombotic microangiopathy. The pathogenic mechanisms are poorly understood, but emerging evidence suggest that excessive neutrophil extracellular trap (NET) formation plays a key role in COVID-19 disease progression. Here, we evaluate if circulating markers of NETs are associated with COVID-19 disease severity and clinical outcome, as well as to markers of inflammation and in vivo coagulation and fibrinolysis. Approach and Results: One hundred six patients with COVID-19 with moderate to severe disease were enrolled shortly after hospital admission and followed for 4 months. Acute and convalescent plasma samples as well as plasma samples from 30 healthy individuals were assessed for markers of NET formation: citrullinated histone H3, cell-free DNA, NE (neutrophil elastase). We found that plasma levels of NET markers were all elevated in patients with COVID-19 relative to healthy controls, were associated with respiratory support requirement and short-term mortality, and declined to those found in healthy individuals 4 months post-infection. Levels of the NET markers also correlated with white blood cells, neutrophils, inflammatory cytokines, and C-reactive protein, as well as to markers of in vivo coagulation, fibrinolysis, and endothelial damage.CONCLUSIONS: Our findings suggest a role of NETs in COVID-19 disease progression, implicating their contribution to an immunothrombotic state. Further, we observed an association between circulating markers of NET formation and clinical outcome, demonstrating a potential role of NET markers in clinical decision-making, as well as for NETs as targets for novel therapeutic interventions in COVID-19.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04402944, NCT04541979, NCT04445285, NCT04432987, NCT04402970.
U2 - 10.1161/ATVBAHA.120.315267
DO - 10.1161/ATVBAHA.120.315267
M3 - Article
C2 - 33267662
SP - 1
EP - 7
JO - Arteriosclerosis thrombosis and vascular biology
JF - Arteriosclerosis thrombosis and vascular biology
SN - 1079-5642
ER -