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

Methods: Longitudinal study of hospitalised and non-hospitalised COVID19 participants 3?16 months post-COVID. Stabilised peripheral blood was processed for mRNAseq and blood neutrophil activation measured by flow cytometry, in addition to other inflammatory markers. K means clustering was used to identify post-COVID subgroups.

Results: 79 patients were included (age 56.7±11.6 (mean±SD) and 48% were male). Post-COVID19, 28 significantly differentially expressed genes (adjusted pvalue<0.05; Wald test with Benjamini-Hochberg correction) were identified between those initially hospitalised (n=49) or not (n=30). Genes relating to neutrophil activity including neutrophil elastase, MPO and azurocidin-1 were upregulated in those who were hospitalised, as well as in those with the highest serum levels of endothelial activation marker, E-selectin. Ongoing fatigue or dyspnoea was more frequent in those who were hospitalised (88%) compared to those who were not (60%) (p=0.0032). Two clusters were identified based on neutrophil surface marker expression in those with ongoing fatigue (cluster 1 (n=10); cluster 2 (n=11)) or dyspnoea (cluster 1 (n=11); cluster 2 (n=11). In both analyses, cluster 2 had significantly higher neutrophil surface expression of activation markers CD11b and CD66b and chemokine receptor CXCR2 compared to cluster 1 and post-COVID individuals with no ongoing symptoms (n=7) (all p<0.01).

Conclusion: Neutrophil activation was identified in individuals with ongoing symptoms post-COVID19 indicating a role for neutrophils in long COVID.