Dysfunctional neutrophil response in COVID-19 infection varies by subtype

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ID: 323367
2026
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Abstract
Abstract 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.
Reference Key
openalex_W7172339863 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Onn Shaun Thein, Kylie B R Belchamber, Jon Hazeldine, Aduragbemi A. Faniyi, Frances Grudzinska, Michael Hughes, Alice Jasper, Kay Por Yip, Louise Crowley, Sebastian T. Lugg, Elizabeth Sapey, David Thickett, Aaron Scott, Dhruv Parekh
Journal journal of leukocyte biology
Year 2026
DOI
10.1093/jleuko/qiag107
URL
https://doi.org/10.1093/jleuko/qiag107
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