PMID- 32511633
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221115
DP  - 2020 Apr 14
TI  - Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19.
LID - 2020.04.09.20059626 [pii]
LID - 10.1101/2020.04.09.20059626 [doi]
AB  - In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia 
      progresses to respiratory failure. Neutrophil extracellular traps (NETs) are 
      extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that 
      are released by neutrophils to contain infections. However, when not properly 
      regulated, NETs have potential to propagate inflammation and microvascular 
      thrombosis, including in the lungs of patients with acute respiratory distress 
      syndrome. While elevated levels of blood neutrophils predict worse outcomes in 
      COVID-19, the role of NETs has not been investigated. We now report that sera 
      from patients with COVID-19 (n=50 patients, n=84 samples) have elevated levels of 
      cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); 
      the latter two are highly specific markers of NETs. Highlighting the potential 
      clinical relevance of these findings, cell-free DNA strongly correlated with 
      acute phase reactants including C-reactive protein, D-dimer, and lactate 
      dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both 
      cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with 
      platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in 
      hospitalized patients receiving mechanical ventilation as compared with 
      hospitalized patients breathing room air. Finally, sera from individuals with 
      COVID-19 triggered NET release from control neutrophils in vitro. In summary, 
      these data reveal high levels of NETs in many patients with COVID-19, where they 
      may contribute to cytokine release and respiratory failure. Future studies should 
      investigate the predictive power of circulating NETs in longitudinal cohorts, and 
      determine the extent to which NETs may be novel therapeutic targets in severe 
      COVID-19.
FAU - Zuo, Yu
AU  - Zuo Y
FAU - Yalavarthi, Srilakshmi
AU  - Yalavarthi S
FAU - Shi, Hui
AU  - Shi H
FAU - Gockman, Kelsey
AU  - Gockman K
FAU - Zuo, Melanie
AU  - Zuo M
FAU - Madison, Jacqueline A
AU  - Madison JA
FAU - Blair, Christopher
AU  - Blair C
FAU - Weber, Andrew
AU  - Weber A
FAU - Barnes, Betsy J
AU  - Barnes BJ
FAU - Egeblad, Mikala
AU  - Egeblad M
FAU - Woods, Robert J
AU  - Woods RJ
FAU - Kanthi, Yogendra
AU  - Kanthi Y
FAU - Knight, Jason S
AU  - Knight JS
LA  - eng
PT  - Preprint
DEP - 20200414
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
UIN - JCI Insight. 2020 Jun 4;5(11):. PMID: 32329756
PMC - PMC7276989
EDAT- 2020/06/09 06:00
MHDA- 2020/06/09 06:01
PMCR- 2020/06/08
CRDT- 2020/06/09 06:00
PHST- 2020/06/09 06:00 [entrez]
PHST- 2020/06/09 06:00 [pubmed]
PHST- 2020/06/09 06:01 [medline]
PHST- 2020/06/08 00:00 [pmc-release]
AID - 2020.04.09.20059626 [pii]
AID - 10.1101/2020.04.09.20059626 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2020 Apr 14:2020.04.09.20059626. doi: 
      10.1101/2020.04.09.20059626.