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Background: NETosis occurs in the context of infection or inflammation and results in the expulsion of decondensed DNA filaments called NETs (Neutrophil Extracellular Traps) into the extracellular environment. NETosis activates coagulation and contributes to the thrombotic risk of inflammatory diseases. To date, two mechanisms of NETosis have been identified: suicidal NETosis, in which neutrophils die after expelling the filaments; and vital NETosis, in which expulsion appears without altering the membrane. Human pregnancy is associated with a mild pro-inflammatory state, which is increased in the event of complications such as preeclampsia (PE). NETosis has been observed in these situations, but the mechanism of its production has not yet been studied. The aim of our study was to evaluate the balance of vital vs. suicidal NETosis in normal pregnancy and in PE.Patients/Methods: Neutrophils from healthy volunteers were stimulated with plasma from normal pregnancies (n = 13) and from women developing preeclampsia (n = 13). Immunofluorescent labelling was performed to determine the percentages and origin of NETs in both groups. Inhibition with suicidal or vital NETosis inhibitors was also performed to validate our results.Results: We found a significant increase in NETs in women with PE compared to women with normal pregnancies. We showed that vital and non-vital NETosis are present in normal and preeclamptic pregnancies. We demonstrated that the higher proportion of NETs observed in PE was due to non-vital NETosis whose main component is represented by suicidal NETosis.Discussion: These results suggest the important part of non-vital NETosis in the pathophysiology of PE.

IntroductionCoronavirus disease 2019 (COVID-19) is a respiratory disease triggered by immunopathological mechanisms that cause excessive inflammation and leukocyte dysfunction. Neutrophils play a critical role in the innate immunity and are able to produce neutrophil extracellular traps (NETs: NETosis process) to combat infections. Some NETs markers are increased in patients who died from COVID-19. Recently, the neutrophil fluorescence variable (NEU-SFL), available on certain automated complete blood count (CBC) analyzers, has been correlated with NET formation and may reflect NETosis in patients. Here we evaluate whether NEU-SFL measured after admission of COVID-19 patients is associated with in-hospital survival or death.Patients and methods1,852 patients admitted for severe COVID-19 at Nîmes University Hospital in 2021 were retrospectively included in the study: 1,564 who survived the hospital stay and 288 who did not. The NEU-SFL was obtained on the Sysmex™ XN-10® analyzer and values for survivors and non-survivors were compared. The intra-patient NEU-SFL variations between the hospital entry and the last day of hospitalization were also analyzed (IRB 22.06.01, NCT 05413824).ResultsNon-survivors presented higher NEU-SFL values. NEU-SFL values above the 4th quartile were independently associated with a 2.88-fold risk of death. Furthermore, the difference of NEU-SFL values between the first and the last available data during hospitalization revealed that a decrease in NEU-SFL was associated to survivors and vice versa.ConclusionOur study reinforces the role of neutrophils and NETosis in the pathophysiology and prognosis of COVID-19. Further studies combining NEU-SFL with other NETosis markers could improve the management of COVID-19 patients.