tetano
Editor, Senior Moderator
J Innate Immun
. 2022 Jan 27;1-16.
doi: 10.1159/000521594. Online ahead of print.
Impaired Degradation of Neutrophil Extracellular Traps: A Possible Severity Factor of Elderly Male COVID-19 Patients
Nicole de Buhr[SUP] 1 2 [/SUP], Ann Christin Parplys[SUP] 3 [/SUP], Maria Schroeder[SUP] 4 [/SUP], Timo Henneck[SUP] 1 2 [/SUP], Berfin Schaumburg[SUP] 3 [/SUP], Stephanie Stanelle-Bertram[SUP] 3 [/SUP], Dominik Jarczak[SUP] 4 [/SUP], Axel Nierhaus[SUP] 4 [/SUP], Jens Hiller[SUP] 5 [/SUP], Sven Peine[SUP] 5 [/SUP], Stefan Kluge[SUP] 4 [/SUP], Karin Klingel[SUP] 6 [/SUP], Gülsah Gabriel[SUP] 3 7 [/SUP], Maren von Köckritz-Blickwede[SUP] 1 2 [/SUP]
Affiliations
Abstract
Neutrophil extracellular traps (NETs) have been described as a potential trigger of severe COVID-19. NETs are known as extracellular DNA fibers released by neutrophils in response to infection. If the host is unable to balance efficient clearance of NETs by dornases (DNases), detrimental consequences occur. Elevated levels of NETs in COVID-19 patients are associated with higher risk of morbid thrombotic complications. Here, we studied the level of NET markers and DNase activity in a cohort of COVID-19 patients compared to healthy controls. Our data confirmed an increased level of NET markers in the plasma of COVID-19 patients, with a higher level in male compared to female patients. At the same time, there was an increased DNase activity detectable in COVID-19 patients compared to healthy controls. Importantly, there was a negative correlation of DNase activity with the age of male patients. The antimicrobial peptide LL-37, which is known to stabilize NETs against DNase degradation, is embedded in NETs upon severe acute respiratory syndrome coronavirus-2-infection. The LL-37 plasma level correlates with the NET-marker level in male COVID-19 patients, indicating a potential role of LL-37 in the risk of NET-associated thrombosis in male COVID-19 patients by stabilizing NETs against DNase degradation. In conclusion, our data identify two potential risk factors of elderly male patients which may lead to inefficient NET degradation and a subsequently higher risk of NET-associated thrombosis during COVID-19: reduced DNase activity and an increased LL-37 level.
Keywords: COVID-19; Elderly male; LL-37; Neutrophil extracellular traps.
. 2022 Jan 27;1-16.
doi: 10.1159/000521594. Online ahead of print.
Impaired Degradation of Neutrophil Extracellular Traps: A Possible Severity Factor of Elderly Male COVID-19 Patients
Nicole de Buhr[SUP] 1 2 [/SUP], Ann Christin Parplys[SUP] 3 [/SUP], Maria Schroeder[SUP] 4 [/SUP], Timo Henneck[SUP] 1 2 [/SUP], Berfin Schaumburg[SUP] 3 [/SUP], Stephanie Stanelle-Bertram[SUP] 3 [/SUP], Dominik Jarczak[SUP] 4 [/SUP], Axel Nierhaus[SUP] 4 [/SUP], Jens Hiller[SUP] 5 [/SUP], Sven Peine[SUP] 5 [/SUP], Stefan Kluge[SUP] 4 [/SUP], Karin Klingel[SUP] 6 [/SUP], Gülsah Gabriel[SUP] 3 7 [/SUP], Maren von Köckritz-Blickwede[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35086104
- DOI: 10.1159/000521594
Abstract
Neutrophil extracellular traps (NETs) have been described as a potential trigger of severe COVID-19. NETs are known as extracellular DNA fibers released by neutrophils in response to infection. If the host is unable to balance efficient clearance of NETs by dornases (DNases), detrimental consequences occur. Elevated levels of NETs in COVID-19 patients are associated with higher risk of morbid thrombotic complications. Here, we studied the level of NET markers and DNase activity in a cohort of COVID-19 patients compared to healthy controls. Our data confirmed an increased level of NET markers in the plasma of COVID-19 patients, with a higher level in male compared to female patients. At the same time, there was an increased DNase activity detectable in COVID-19 patients compared to healthy controls. Importantly, there was a negative correlation of DNase activity with the age of male patients. The antimicrobial peptide LL-37, which is known to stabilize NETs against DNase degradation, is embedded in NETs upon severe acute respiratory syndrome coronavirus-2-infection. The LL-37 plasma level correlates with the NET-marker level in male COVID-19 patients, indicating a potential role of LL-37 in the risk of NET-associated thrombosis in male COVID-19 patients by stabilizing NETs against DNase degradation. In conclusion, our data identify two potential risk factors of elderly male patients which may lead to inefficient NET degradation and a subsequently higher risk of NET-associated thrombosis during COVID-19: reduced DNase activity and an increased LL-37 level.
Keywords: COVID-19; Elderly male; LL-37; Neutrophil extracellular traps.