Background: Neutrophil activation biomarkers have been highlighted as key components of SARS-CoV-2 infection severity and multisystemic manifestations. However, their implication in the development of respiratory sequelae is unknown. Thus, we aimed to assess these biomarkers in the first 6 months after a SARS-CoV-2 infection.

 Methods: We prospectively included all patients hospitalized for SARS-CoV-2 severe-to-critical infection and re-assessed them at three and six months. Biological markers were assessed at each visit and included measurement of neutrophil activation (neutrophil elastase, myeloperoxydase-DNA, histone-DNA, cell-free DNA and DNAse). Moreover, CXCR2 plays a critical role in the regulation of neutrophil homeostasis. Functional signs, pulmonary function tests, a six-minute walk test, a one-minute sit-to-stand test and a chest computed tomography were also performed. 

Results: Of the 98 patients included, 82 were assessed at three months and 65 at six months after hospital discharge. At 3 and 6 months, blood levels of neutrophil elastase, MPO-DNA, histone-DNA and cell-free DNA were significantly higher in patients than in healthy controls (p<0.0001). DNAse showed a significant decrease compared to healthy controls (p<0.0001). CXCR2 blood levels at three months were higher in patients with respiratory sequelae.

Conclusion: When compared to healthy controls, neutrophil activation biomarkers remain at dramatical rates at least 6 months after SARS-CoV-2 infection. More studies are needed to assess their impact, in particular CXCR2, in the long development of respiratory and systemic sequelae, before considering targeted therapies.