tetano
Editor, Senior Moderator
PLoS One
. 2026 Nov 3;21(11):e0360244.
doi: 10.1371/journal.pone.0360244. eCollection 2026.
Jason Canizales Galaviz 1 , Amir Khan 1 , Bochra Tourki 2 , Susannah Patarroyo-White 1 , Nathan H Johnson 1 , Alejandro Arjona 1 , Christian Bime 3 , Kenneth S Knox 3 , Mehdi S Mirsaeidi 4 , Brenda Juan Guardela 2 , Jose D Herazo-Maya 2 , Nancy G Casanova 1 , Joe G N Garcia 1
Affiliations Expand
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.
. 2026 Nov 3;21(11):e0360244.
doi: 10.1371/journal.pone.0360244. eCollection 2026.
eNAMPT is a plasma biomarker of COVID-19 severity and ARDS progression linked to increased immune effector cell expression
Jason Canizales Galaviz 1 , Amir Khan 1 , Bochra Tourki 2 , Susannah Patarroyo-White 1 , Nathan H Johnson 1 , Alejandro Arjona 1 , Christian Bime 3 , Kenneth S Knox 3 , Mehdi S Mirsaeidi 4 , Brenda Juan Guardela 2 , Jose D Herazo-Maya 2 , Nancy G Casanova 1 , Joe G N Garcia 1
Affiliations Expand
- PMID: 42976129
- PMCID: PMC13730375
- DOI: 10.1371/journal.pone.0360244
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.