Plasma NET Markers Kinetics in COVID-19 Patients Receiving Immunomodulatory Treatments: a Cohort Study

Background: in COVID-19, dexamethasone (DXM) and tocilizumab are used to alleviate inflammation in patients requiring oxygen support. Several evidences support a role of increased immunothrombosis and NETosis in particular, in the pathogenesis of disease severity. Whether the use of immunomodulatory drugs has any impact on NETosis is currently unknown. The potential beneficial effect of immunomodulatory drugs as early treatment in mild patients is being investigated in the COVERAGE trial (NCT04356495). Objective: we aimed to characterize the kinetics of plasma NET markers in COVID-19 patients receiving immunomodulatory treatments. Methods: one hundred and sixty-six early (≤ 7 days) COVID-19 outpatients were randomly allocated to placebo group (79 i.e. 48%), inhaled ciclesonide (48 i.e. 29%) or inhaled IFN-β-1b (39 i.e. 23%). Fifty-nine critically ill patients were included: 8 received placebo (14%), 42 (71%) DXM (6mg i.v. for ten days) and nine (15%) DXM + tocilizumab (8mg/kg i.v.). We quantified NET markers (MPO-DNA, H3Cit, H3cit-DNA) in plasma at inclusion and Day 7 for outpatients, and at inclusion, Day 3 and Day 7 for critically ill patients Results: inhaled IFN-β-1b, but not inhaled ciclesonide nor placebo, was linked to a decrease in plasma H3Cit levels (p: 0.02). DXM, alone and in association, was not linked to a decrease in plasma NET markers levels in critically ill patients. Conclusion: use of immunomodulatory treatments is not linked to a decrease in plasma NET markers in COVID-19 patients, except for inhaled IFN-β-1b in early mild outpatients. Adjunction of treatment targeting NETosis might so be an interesting therapeutic approach in COVID-19 patients.