eNAMPT is a plasma biomarker of COVID-19 severity and ARDS progression linked to increased immune effector cell expression
4 affiliations
- 1Center for Inflammation Science and Systems Medicine, The Herbert Wertheim University of Florida Scripps Research Institute, Jupiter, Florida, United States of America
- 2Division of Pulmonary, Critical Care and Sleep Medicine. Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Ubben Center for Pulmonary Fibrosis Research, Tampa, Florida ., United States of America
- 3University of Arizona College of Medicine, Phoenix, Arizona, United States of America
- 4Division of Pulmonary, Critical Care and Sleep Medicine, University of Texas at Austin, Austin, Texas . United States of America
Abstract
Background: The COVID-19 pandemic highlighted the critical unmet need for novel targets, biomarkers, and effective pharmacotherapies to reduce the severity/mortality of COVID pneumonia and progression to acute respiratory distress syndrome (ARDS). Extracellular NAMPT (eNAMPT) is a druggable DAMP and TLR4 ligand centrally involved in ARDS pathobiology. We explored the utility of plasma eNAMPT measurements as a potential COVID-19 biomarker linked to ARDS progression and disease severity and investigated the potential cellular source for eNAMPT release/secretion in COVID-19 subjects. Methods: A plasma biomarker panel of inflammatory cytokines (IL-1β, IL-6, IL-8, IL-1RA, TNF-α), DAMPs (eNAMPT, MIF) and vascular proteins (ANG-2, PSGL-1) were evaluated in three distinct COVID-19-positive cohorts (Miami, Arizona, Tampa) (n = 277) and healthy control subjects (n = 214). Single-cell RNA sequencing (scRNA-seq) publicly available on peripheral blood mononuclear cells (PBMCs) in a subset of Tampa COVID-19 survivors (n = 18) and an autopsied COVID lung tissue database was separately analyzed for biomarker gene expression. Results: Plasma biomarkers, including eNAMPT were significantly elevated in COVID-19 subjects compared to healthy controls (p < 0.0001), with IL-1RA, IL-6 and eNAMPT exhibiting the strongest diagnostic performance. Biomarker levels (all except IL-8, MIF) were higher in COVID-19 ARDS cases vs COVID-19 pneumonia (n = 154, AUC 0.71–0.79, p < 0.05) and were significantly elevated in COVID non-survivors (IL-6, IL-1RA, TNF-α, eNAMPT, ANG-2, PSGL-1) compared to survivors (p < 0.05). NAMPT gene expression was significantly upregulated in COVID-19 PBMCs compared with healthy controls, most evident within the CD14 + monocyte cluster. Relative to lung tissue from non-COVID-19 infected, NAMPT gene expression was increased in specific COVID-19 lung cell populations, including neutrophils, CD16 + monocytes, conventional dendritic cells (cDCs), fibroblasts, endothelium, and alveolar macrophages. Conclusion: Our study corroborated the utility of this biomarker panel for diagnostic and severity assessment in COVID-19- associated ARDS and as a strategy for subject stratification in therapeutic trials of eNAMPT-neutralizing therapies. We further identified NAMPT expression in immune effector cells that correlates with COVID-19 severity and lethality. Together, these findings suggest NAMPT plays a key role in sustaining inflammatory activation and impairing lung regeneration in fatal COVID-19.
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BibTeX
@article{galaviz2026enampt,
title = {{eNAMPT is a plasma biomarker of COVID-19 severity and ARDS progression linked to increased immune effector cell expression}},
author = {Jason Canizales Galaviz and Amir Khan and Bochra Tourki and Susannah Patarroyo-White and Nathan H. Johnson and Alejandro Arjona and Christian Bime and Kenneth S. Knox and Mehdi S. Mirsaeidi and Brenda Juan Guardela and Jose D. Herazo-Maya and Nancy G. Casanova and Joe G. N. Garcia},
journal = {PLOS One},
year = {2026},
month = nov,
doi = {10.1371/journal.pone.0360244},
url = {https://doi.org/10.1371/journal.pone.0360244},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - eNAMPT is a plasma biomarker of COVID-19 severity and ARDS progression linked to increased immune effector cell expression
AU - Jason Canizales Galaviz
AU - Amir Khan
AU - Bochra Tourki
AU - Susannah Patarroyo-White
AU - Nathan H. Johnson
AU - Alejandro Arjona
AU - Christian Bime
AU - Kenneth S. Knox
AU - Mehdi S. Mirsaeidi
AU - Brenda Juan Guardela
AU - Jose D. Herazo-Maya
AU - Nancy G. Casanova
AU - Joe G. N. Garcia
PY - 2026
DA - 2026/11/03
JO - PLOS One
DO - 10.1371/journal.pone.0360244
UR - https://doi.org/10.1371/journal.pone.0360244
AB - Background: The COVID-19 pandemic highlighted the critical unmet need for novel targets, biomarkers, and effective pharmacotherapies to reduce the severity/mortality of COVID pneumonia and progression to acute respiratory distress syndrome (ARDS). Extracellular NAMPT (eNAMPT) is a druggable DAMP and TLR4 ligand centrally involved in ARDS pathobiology. We explored the utility of plasma eNAMPT measurements as a potential COVID-19 biomarker linked to ARDS progression and disease severity and investigated the potential cellular source for eNAMPT release/secretion in COVID-19 subjects. Methods: A plasma biomarker panel of inflammatory cytokines (IL-1β, IL-6, IL-8, IL-1RA, TNF-α), DAMPs (eNAMPT, MIF) and vascular proteins (ANG-2, PSGL-1) were evaluated in three distinct COVID-19-positive cohorts (Miami, Arizona, Tampa) (n = 277) and healthy control subjects (n = 214). Single-cell RNA sequencing (scRNA-seq) publicly available on peripheral blood mononuclear cells (PBMCs) in a subset of Tampa COVID-19 survivors (n = 18) and an autopsied COVID lung tissue database was separately analyzed for biomarker gene expression. Results: Plasma biomarkers, including eNAMPT were significantly elevated in COVID-19 subjects compared to healthy controls (p < 0.0001), with IL-1RA, IL-6 and eNAMPT exhibiting the strongest diagnostic performance. Biomarker levels (all except IL-8, MIF) were higher in COVID-19 ARDS cases vs COVID-19 pneumonia (n = 154, AUC 0.71–0.79, p < 0.05) and were significantly elevated in COVID non-survivors (IL-6, IL-1RA, TNF-α, eNAMPT, ANG-2, PSGL-1) compared to survivors (p < 0.05). NAMPT gene expression was significantly upregulated in COVID-19 PBMCs compared with healthy controls, most evident within the CD14 + monocyte cluster. Relative to lung tissue from non-COVID-19 infected, NAMPT gene expression was increased in specific COVID-19 lung cell populations, including neutrophils, CD16 + monocytes, conventional dendritic cells (cDCs), fibroblasts, endothelium, and alveolar macrophages. Conclusion: Our study corroborated the utility of this biomarker panel for diagnostic and severity assessment in COVID-19- associated ARDS and as a strategy for subject stratification in therapeutic trials of eNAMPT-neutralizing therapies. We further identified NAMPT expression in immune effector cells that correlates with COVID-19 severity and lethality. Together, these findings suggest NAMPT plays a key role in sustaining inflammatory activation and impairing lung regeneration in fatal COVID-19.
SN - 1932-6203
ER -