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BRIEF RESEARCH REPORT article

Front. Cell. Infect. Microbiol.

Sec. Molecular Bacterial Pathogenesis

Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1636463

This article is part of the Research TopicImmunometabolic circuits in host-pathogen interactionView all articles

Expression of Metabolic Genes in NK Cells is Associated with Clinical Outcomes in Patients with Severe COVID-19: A Brief Report

Provisionally accepted
Kenia  Y Osuna-EspinozaKenia Y Osuna-Espinoza1Manuel  G Mejía-TorresManuel G Mejía-Torres1Adrian  Camacho-OrtizAdrian Camacho-Ortiz1Eduardo  Perez-AlbaEduardo Perez-Alba1Azalia  M Martinez-CastillaAzalia M Martinez-Castilla1Mario  C Salinas-CarmonaMario C Salinas-Carmona1Adrian  G Rosas-TaracoAdrian G Rosas-Taraco1,2*
  • 1Universidad Autónoma de Nuevo León, Servicio y Departamento de Inmunología. Facultad de Medicina, Monterrey, Mexico
  • 2Autonomous University of Nuevo León, San Nicolás de los Garza, Mexico

The final, formatted version of the article will be published soon.

Natural killer (NK) cells are innate lymphocytes with cytotoxic activity against tumors and viruses.The pandemic of the coronavirus disease 2019 (COVID-19) has increased the investigation of their role in disease severity. However, their functional status and modulators remain controversial. Recent studies highlighted the role of metabolism in immune function, but metabolic changes in NK cells during SARS-CoV-2 infection remain unexplored. This study compares metabolic (SIRT1, AMPKA, HIF1A, and GLUT1) and inflammatory (NFKB1, NFKB1A, IFNG, and SOCS1) gene expression, and flow cytometry-based assessment of functional markers in NK cells from severe COVID-19 patients (n=15) and the control group (n=10), and their association with clinical outcomes. Severe COVID-19 patients exhibited elevated IFNg, Granzyme B, and KIR2DL1 expression in NK cells compared to controls (P < 0.005), while LAMP1 was unchanged (P > 0.05). NK cells from deceased patients exhibited significantly lower expression levels of LAMP1 and Granzyme B (P < 0.05). Patients hospitalized >7 days presented lower Granzyme-B+ NK cells (P < 0.05). NK cells from severe COVID-19 patients showed downregulation of HIF1A and GLUT1, and upregulation of NFKB1 (P < 0.05). HIF1A and GLUT1 expression were elevated in patients with >7 days of hospitalization (P < 0.05). SIRT1 expression was higher in patients requiring intubation (P < 0.05). SIRT1, HIF1A, and GLUT1 were upregulated in deceased patients (P < 0.05). In conclusion, we demonstrate that NK cells from patients with severe COVID-19 exhibit increased functional markers and dysregulated metabolic gene expression associated with clinical outcomes.

Keywords: Severe COVID-19, NK cells, Metabolism, SIRT1, AMPK, HIF1A, GLUT1

Received: 27 May 2025; Accepted: 28 Jul 2025.

Copyright: © 2025 Osuna-Espinoza, Mejía-Torres, Camacho-Ortiz, Perez-Alba, Martinez-Castilla, Salinas-Carmona and Rosas-Taraco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Adrian G Rosas-Taraco, Autonomous University of Nuevo León, San Nicolás de los Garza, Mexico

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