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Background <p>Acute community-acquired pneumonia (CAP) is a leading cause of infection-related mortality worldwide. Endotoxemia, characterized by elevated plasma lipopolysaccharide (LPS), is a key driver of inflammation and thrombosis in Gram-negative sepsis and has been suggested to occur in severe pneumonia, irrespective of etiology. However, current immunoassays for LPS quantification lack sensitivity and specificity. We aimed to quantify plasma LPS in severe CAP patients, including COVID-19, using a validated mass spectrometry method, and to explore associations with immune activation, coagulation, gut translocation, and clinical outcomes.</p> Methods <p>In this prospective ancillary study of the LYMPHONIE cohort, we included 34 non-COVID-19 severe CAP (sCAP), 34 severe COVID-19 (sCOVID-19) and 34 matched healthy volunteers. Plasma LPS was measured by LC–MS/MS detecting 3-hydroxy fatty acids of lipid A. Clinical data, immune biomarkers, coagulation biomarkers, and gut injury markers were measured.</p> Results <p>Unexpectedly, median plasma LPS concentrations were significantly lower in sCAP patients (724&#xa0;pmol/ml in sCAP; 750&#xa0;pmol/ml in sCOVID-19) compared to healthy volunteers (1009&#xa0;pmol/ml, <i>p</i> &lt; 0.001). LPS levels did not correlate with severity scores or mortality. Low positive correlations were observed between LPS and markers of endothelial activation (sVCAM-1) and coagulation (D-dimer). However, patients with high LPS showed no increased risk of thrombotic or cardiovascular events.</p> Conclusions <p>Using a highly specific LC–MS/MS method, we found no evidence of increased circulating LPS in severe pneumonia patients, challenging the hypothesis of gut-derived endotoxemia as a major contributor to systemic inflammation in severe CAP, including COVID-19.</p> <p><Emphasis Type="BoldItalic">Take-home message</Emphasis> Using a highly specific mass-spectrometry assay, we found no evidence of elevated circulating lipopolysaccharide in severe community-acquired pneumonia, including COVID-19. These findings challenge the concept that gut-derived endotoxemia is a major driver of systemic inflammation in severe pneumonia.</p> <p><Emphasis Type="BoldItalic">Tweet</Emphasis> Mass spectrometry reveals no rise in plasma LPS in severe pneumonia or COVID-19, questioning gut endotoxemia’s role in inflammation.</p>

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Endotoxemia and its association with immune and coagulopathy responses in severe community-acquired pneumonia and COVID-19

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月9日

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  • Mathieu Blot,
  • Amadou-Khalilou Sow,
  • David Masson,
  • Maxime Nguyen,
  • Marine Jacquier,
  • Jean-Paul Pais de Barros,
  • Thibault Sixt,
  • Maxime Luu,
  • Pierre-Emmanuel Charles,
  • Lionel Piroth,
  • Jean Pierre Quenot,
  • Christine Binquet,
  • Jean-Pierre Quenot,
  • Pierre-Emmanuel Charles,
  • Marine Jacquier,
  • Pascal Andreu,
  • Marie Labruyère,
  • Jean-Baptiste Roudaut,
  • Sébastien Prin,
  • Jose Pineda,
  • Alicia Taha,
  • Philippe Bonniaud,
  • Marjolaine Georges,
  • Guillaume Beltramo,
  • Bernard Bonnotte,
  • Hervé Devilliers,
  • Jérémy Barben,
  • Lionel Piroth,
  • Thibaut Sixt,
  • Julien Guy,
  • Christine Binquet,
  • Abderrahmane Bourredjem,
  • Amadou-Khalilou Sow,
  • Florine Cattin,
  • Marc Bardou,
  • Maxime Luu,
  • Ines Ben Ghezala,
  • Karen Sagorny,
  • Julie Ferrandes,
  • Joao Pais-De-Barros,
  • Hélène Choubley,
  • Victoria Bergas,
  • Julie Maréchal,
  • Laure Stiel,
  • Sylvie Nguyen,
  • Mathieu Blot

摘要

Background

Acute community-acquired pneumonia (CAP) is a leading cause of infection-related mortality worldwide. Endotoxemia, characterized by elevated plasma lipopolysaccharide (LPS), is a key driver of inflammation and thrombosis in Gram-negative sepsis and has been suggested to occur in severe pneumonia, irrespective of etiology. However, current immunoassays for LPS quantification lack sensitivity and specificity. We aimed to quantify plasma LPS in severe CAP patients, including COVID-19, using a validated mass spectrometry method, and to explore associations with immune activation, coagulation, gut translocation, and clinical outcomes.

Methods

In this prospective ancillary study of the LYMPHONIE cohort, we included 34 non-COVID-19 severe CAP (sCAP), 34 severe COVID-19 (sCOVID-19) and 34 matched healthy volunteers. Plasma LPS was measured by LC–MS/MS detecting 3-hydroxy fatty acids of lipid A. Clinical data, immune biomarkers, coagulation biomarkers, and gut injury markers were measured.

Results

Unexpectedly, median plasma LPS concentrations were significantly lower in sCAP patients (724 pmol/ml in sCAP; 750 pmol/ml in sCOVID-19) compared to healthy volunteers (1009 pmol/ml, p < 0.001). LPS levels did not correlate with severity scores or mortality. Low positive correlations were observed between LPS and markers of endothelial activation (sVCAM-1) and coagulation (D-dimer). However, patients with high LPS showed no increased risk of thrombotic or cardiovascular events.

Conclusions

Using a highly specific LC–MS/MS method, we found no evidence of increased circulating LPS in severe pneumonia patients, challenging the hypothesis of gut-derived endotoxemia as a major contributor to systemic inflammation in severe CAP, including COVID-19.

Take-home message Using a highly specific mass-spectrometry assay, we found no evidence of elevated circulating lipopolysaccharide in severe community-acquired pneumonia, including COVID-19. These findings challenge the concept that gut-derived endotoxemia is a major driver of systemic inflammation in severe pneumonia.

Tweet Mass spectrometry reveals no rise in plasma LPS in severe pneumonia or COVID-19, questioning gut endotoxemia’s role in inflammation.