TY - JOUR
T1 - NETosis induction reflects COVID-19 severity and long COVID
T2 - insights from a 2-center patient cohort study in Israel
AU - Krinsky, Nitzan
AU - Sizikov, Sofia
AU - Nissim, Sivan
AU - Dror, Adi
AU - Sas, Anna
AU - Prinz, Hodaya
AU - Pri-Or, Ester
AU - Perek, Shay
AU - Raz-Pasteur, Ayelet
AU - Lejbkowicz, Izabella
AU - Cohen-Matsliah, Sivan Ida
AU - Almog, Ronit
AU - Chen, Nikanor
AU - Kurd, Ramzi
AU - Jarjou'i, Amir
AU - Rokach, Ariel
AU - Ben-Chetrit, Eli
AU - Schroeder, Avi
AU - Caulin, Aleah F.
AU - Yost, Christian Con
AU - Schiffman, Joshua D.
AU - Goldfeder, Mor
AU - Martinod, Kimberly
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/9
Y1 - 2023/9
N2 - Background: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality. Objectives: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID. Methods: One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: acute COVID-19 (mild/moderate, severe/critical), convalescent COVID-19 (recovered and long COVID), along with 54 non-COVID controls. Plasma was examined for markers of platelet activation, coagulation, and NETs. Ex vivo NETosis induction capability was evaluated after neutrophil incubation with patient plasma. Results: Soluble P-selectin, factor VIII, von Willebrand factor, and platelet factor 4 were significantly elevated in patients with COVID-19 versus controls. Myeloperoxidase (MPO)-DNA complex levels were increased only in severe COVID-19 and did not differentiate between COVID-19 severities or correlate with thrombotic markers. NETosis induction levels strongly correlated with illness severity/duration, platelet activation markers, and coagulation factors, and were significantly reduced upon dexamethasone treatment and recovery. Patients with long COVID maintained higher NETosis induction, but not NET fragments, compared to recovered convalescent patients. Conclusions: Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID. Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.
AB - Background: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality. Objectives: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID. Methods: One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: acute COVID-19 (mild/moderate, severe/critical), convalescent COVID-19 (recovered and long COVID), along with 54 non-COVID controls. Plasma was examined for markers of platelet activation, coagulation, and NETs. Ex vivo NETosis induction capability was evaluated after neutrophil incubation with patient plasma. Results: Soluble P-selectin, factor VIII, von Willebrand factor, and platelet factor 4 were significantly elevated in patients with COVID-19 versus controls. Myeloperoxidase (MPO)-DNA complex levels were increased only in severe COVID-19 and did not differentiate between COVID-19 severities or correlate with thrombotic markers. NETosis induction levels strongly correlated with illness severity/duration, platelet activation markers, and coagulation factors, and were significantly reduced upon dexamethasone treatment and recovery. Patients with long COVID maintained higher NETosis induction, but not NET fragments, compared to recovered convalescent patients. Conclusions: Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID. Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.
KW - COVID-19
KW - extracellular traps
KW - immunothrombosis
KW - neutrophil
KW - post-acute COVID-19 syndrome
UR - http://www.scopus.com/inward/record.url?scp=85160101688&partnerID=8YFLogxK
U2 - 10.1016/j.jtha.2023.02.033
DO - 10.1016/j.jtha.2023.02.033
M3 - Article
C2 - 37054916
AN - SCOPUS:85160101688
SN - 1538-7933
VL - 21
SP - 2569
EP - 2584
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 9
ER -
