AUTHOR=Yasseen Basma A. , Elkhodiry Aya A. , El-sayed Hajar , Zidan Mona , Kamel Azza G. , Badawy Mohamed A. , Hamza Marwa S. , El-Messiery Riem M. , El Ansary Mohamed , Abdel-Rahman Engy A. , Ali Sameh S. TITLE=The role of neutrophilia in hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality outcome in critically ill COVID-19 patients JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 11 - 2024 YEAR=2025 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1510592 DOI=10.3389/fmolb.2024.1510592 ISSN=2296-889X ABSTRACT=IntroductionCOVID-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.MethodsBased 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.ResultsArterial 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.ConclusionThis indicates the role of neutrophilia in hyperlactatemia and lung damage, subsequently contributing to mortality outcomes in severe SARS-CoV-2 infection.