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. 2025 Apr 17:15:1508120.
doi: 10.3389/fcimb.2025.1508120. eCollection 2025.

Different patterns of leukocyte immune responses to infection of ancestral SARS-CoV-2 and its variants

Yuanyuan Wu  1 , Raphael Serna  1 , Wenqi Gan  2 , Zhichao Fan  1
Affiliations

Different patterns of leukocyte immune responses to infection of ancestral SARS-CoV-2 and its variants

Yuanyuan Wu et al. Front Cell Infect Microbiol. .

Abstract

Background: Contributions 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.

Methods: We 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.

Results: We 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.

Conclusions: Our findings provided insights into different leukocyte immune responses to ancestral SARS-CoV-2, Delta, and Omicron variants.

Keywords: COVID-19; SARS-CoV-2 variant; leukocyte; lymphocyte; monocyte; neutrophil.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Multiple linear regression analysis of leukocyte levels in COVID-19 survivors and decedents compared to non-COVID-19 control subjects for 2020 (mainly ancestral strain), 2021 (mainly Delta variant), and 2022 (mainly Omicron variant). Total leukocytes (A, F, K), neutrophils (B, G, L), immature granulocytes (C, H, M), lymphocytes (D, I, N), and monocytes (E, J, O) indicate changes of significant difference in 2020 (A-E), 2021 (F-J) and 2022 (K-O). Data are presented as mean ± SD. ns, P>0.05, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Figure 2
Figure 2
Multiple linear regression analysis of leukocyte levels in COVID-19 survivors (upper) and decedents (lower) infected with the ancestral strain, Delta variant, and Omicron variant. Total leukocytes (A, F), neutrophils (B, G), immature granulocytes (C, H), lymphocytes (D, I), and monocytes (E, J). Data are presented as mean ± SD. ns, P>0.05, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
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