Introduction: Neutrophilic inflammation is associated with acute COVID19 pathology, however, their involvement in symptoms post-COVID19 remains unknown

Method: Longitudinal study of hospitalised and non-hospitalised COVID19 participants up to 29 days post-hospitalisation and 3-12 months post-COVID19. In acute COVID19, serum neutrophil-associated proteins were measured by ELISA. Peripheral blood neutrophil activation and functional surface markers were analysed by flow cytometry post-COVID19. Any ongoing symptoms including dyspnoea, cough, fever, headache, fatigue, muscle aches, and palpitations, at time of blood sampling were recorded.

Results: In acute COVID-19, myeloperoxidase and neutrophil extracellular trap-associated marker CitH3 were significantly higher in patients still hospitalised at day 29 (n=14) compared with those discharged (n=79) (p=0.012; p=0.019). Post-COVID19, neutrophil chemokine receptor CXCR2 was significantly elevated in patients with >1 symptom (n=15, p=0.022) compared to those with ≤1 (n=26). In participants with fatigue or >1 symptom the relationships between neutrophil markers were altered, with stronger positive correlations observed between CXCR2 and activation markers CD11b (R=0.51, p=0.007; R=0.54, p=0.004) and CD66b (R=0.46, p=0.014; R=0.49, p=0.01) and between CD66b and the P-selectin receptor, PSGL1, with the largest positive shift in the latter observed in those with dyspnoea (R=0.59, p=0.002), compared to those without.

Conclusion: Upregulation of chemokine receptors and a shift in activation markers suggests a more activated and mature phenotype post-COVID19, warranting further investigation of neutrophils as therapeutic targets in long-COVID.