AUTHOR=Wu Yuanyuan , Serna Raphael , Gan Wenqi , Fan Zhichao TITLE=Different patterns of leukocyte immune responses to infection of ancestral SARS-CoV-2 and its variants JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1508120 DOI=10.3389/fcimb.2025.1508120 ISSN=2235-2988 ABSTRACT=BackgroundContributions of leukocytes to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) defense have been reported extensively. However, it remains unclear whether there are different leukocyte responses to ancestral SARS-CoV-2 and its variants.MethodsWe analyzed peripheral blood leukocyte and subtype concentrations from 575 COVID-19 patients and 950 non-COVID-19 subjects registered at the University of Connecticut John Dempsey Hospital between 2020 and 2022, which covers the ancestral strain, Delta, and Omicron variants.ResultsWe found that neutrophils, immature granulocytes, and monocytes were elevated, and lymphocytes were reduced after infection. These hyperactive neutrophils/immature granulocytes and suppressed lymphocytes/monocytes were associated with poorer prognosis in ancestral strain infection. Different from the ancestral strain, hyperactive immature granulocytes were not shown in the decedents of Delta infection, and immature granulocyte concentration was not observed to be associated with mortality. In Omicron infection, suppressed lymphocytes and monocytes were not shown in the decedents, and lymphocyte/monocyte concentrations were not associated with mortality.ConclusionsOur findings provided insights into different leukocyte immune responses to ancestral SARS-CoV-2, Delta, and Omicron variants.