Dysfunctional neutrophil response in COVID-19 infection varies by subtype

The SARS-CoV-2 virus significantly evolved with several new strains identified. Transmissibility has increased with each strain, corresponding with a decrease in mortality. We previously demonstrated novel dysfunctional neutrophil responses in alpha COVID-19 patients compared to community acquired pneumonia controls. We investigated if strain variation altered our previously observed neutrophil dysfunction. Patients with COVID-19 not requiring intensive care were recruited between January 2021 and May 2022 from the Queen Elizabeth Hospital Birmingham; 41 patients with alpha, 32 delta and 14 omicron. Neutrophils isolated from whole blood were investigated for phagocytosis of labelled Streptococcus pneumoniae, transwell migration towards interleukin-8, neutrophil extracellular (NET) formation and surface phenotype. Neutrophil phagocytosis was significantly increased in delta variant (vs alpha p=0.0012, vs omicron p=0.0209). Transwell migration was also significantly reduced in omicron patients (vs alpha p=0.0002, vs delta p=0.0129). There was a significant reduction in NET formation from omicron patients (vs alpha p=0.0031, vs delta p=0.0231). Compared to alpha patients, neutrophils from omicron patients had reduced expression of CD10 (p=0.0004), CD54 (p=0.0015), CD62L (p=0.0013) and CD11c (p<0.0001). CXCR2 expression was higher in neutrophils from omicron compared to alpha patients (p=0.0001). Neutrophil function and phenotype differ between the variants of COVID-19 infection in hospitalised patients. Neutrophil changes suggest more accurate migration in omicron patients, leading to decreased neutrophil host-mediated tissue damage. This may contribute to the overall milder clinical omicron phenotype. Ongoing research and review of therapies remains important alongside viral evolution.