ABSTRACT
Introduction: Neutrophil extracellular traps (NETs) have recently been linked to an important role in the pathogenesis of Covid-19. Method(s): Prospective observational study of 91 hospitalized patients. We studied longitudinally the viral phase, early inflammatory and late, and the 4 most specific components of NETs: cell free-DNA (cfDNA), MPO-DNA and NE-DNA complexes and citrullinated Histone 3 (citH3). Result(s): We observed elevated levels vs controls of MPO-DNA and NE-DNA complexes and cfDNA at admission and in the 3 phases of the disease. CitH3 was elevated from the early inflammatory phase onwards. There was a significant correlation in survivors (r=0.798) and in all severity degrees between MPO and NE and between cfDNA and H3 cit (r=0.3), but not in the rest of combinations among the 4, nor in dead patients. We did not observe any correlation in any group between MPO or NE with citH3. There was an increase of only cfDNA levels in more severe patients. The area under the ROC curve for critical severity and mortality was high for cfDNA (0.7327 and 0.7482) and much poorer for the other 3 NETs markers. Conclusion(s): -We found evidence of neutrophil activation of NETs components in Covid-19, during the 3 phases of the disease, but without a clear relationship with severity and mortality. -cfDNA was related to severity and mortality, and its sources appeared to be more related to tissue damage than to NETs -The best correlation between them was MPO-NE, and these more neutrophil-specific markers reflect probably better NET formation. NETs role has maybe been overestimated using other less specific markers.