The role of neutrophilia in hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality outcome in critically ill COVID-19 patients

Basma A Yasseen; Aya A Elkhodiry; Hajar El-Sayed; Mona Zidan; Azza G Kamel; Mohamed A Badawy; Marwa S Hamza; Riem M El-Messiery; Mohamed El Ansary; Engy A Abdel-Rahman; Sameh S Ali

doi:10.3389/fmolb.2024.1510592

The role of neutrophilia in hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality outcome in critically ill COVID-19 patients

Front Mol Biosci. 2025 Jan 6:11:1510592. doi: 10.3389/fmolb.2024.1510592. eCollection 2024.

Authors

Affiliations

¹ Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
² Department of Clinical Pharmacy Practice, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt.
³ Infectious Disease Unit, Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
⁴ Department of Intensive Care, Faculty of Medicine, Cairo University, Cairo, Egypt.
⁵ Pharmacology Department, Faculty of Medicine, Assuit University, Assuit, Egypt.

^# Contributed equally.

Abstract

Introduction: COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis, yet the key players driving this association remain unclear. It is generally assumed that organ damage causes toxic acidosis, but since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes, we asked if metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients.

Methods: Based on prospective mortality outcome, critically ill COVID-19 patients were divided into ICU- survivors and ICU-non-survivors. Samples were analyzed to explore if correlations exist between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils, platelets, and PBMCs for glycolytic activities.

Results: Arterial blood gas analyses showed remarkable hypoxemia in non-survivors with no consistent differences in PCO₂ or [HCO₃ ^-]. The hemoglobin oxygen dissociation curve revealed a right-shift, consistent with lower blood-pH and elevated blood lactate in non-survivors. Metabolic analysis of different blood cells revealed increased glycolytic activity only when considering the total number of neutrophils.

Conclusion: This indicates the role of neutrophilia in hyperlactatemia and lung damage, subsequently contributing to mortality outcomes in severe SARS-CoV-2 infection.

Keywords: COVID-19 mortality; acidosis; lactate; lung damage; neutrophils.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Association of Friends of the National Cancer Institute, the Children’s Cancer Hospital Foundation grant number: SA-COVID-01, Science and Technology Development Fund, Grant number: 49,561, and the Academy of Scientific Research and Technology, grant number: RESPECT-10018. All funds were granted to SSA. We would like to acknowledge Egypt Cancer Network ECN-US for funding the publication of this project.