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<p>Ectonucleotidases regulate extracellular purine signaling and play a key role in inflammation and thrombosis, two major components of COVID-19 pathophysiology. We investigated the enzymatic activities of CD39 (NTPDase1) and CD73 (ecto-5’-nucleotidase) as potential biomarkers of disease severity. Patients with RT-PCR-confirmed COVID-19 were enrolled between August 1st, 2020, and August 1st, 2021, and stratified into mild to moderate (MM, <i>n</i> = 55) or severe to critical (SC, <i>n</i> = 30) groups according to WHO criteria. Serum samples were collected on days 1, 3, and 7 following Emergency Department (ED) admission. CD39 and CD73 activities were measured by HPLC using etheno-fluorescent nucleotide substrates and compared to healthy volunteers (HV, <i>n</i> = 30) matched for age and sex. Serum CD73 activity was significantly elevated in COVID-19 patients compared to HV (MM: 76 ± 9.4; SC: 99 ± 21 vs. HV: 25 ± 2.7 pmol/min/µL; <i>p</i> &lt; 0.0001), particularly in patients requiring ≥ 6&#xa0;L/min oxygen (<i>p</i> = 0.005) or with a respiratory rate &gt; 20/min (<i>p</i> = 0.02). CD73 activity remained elevated throughout hospitalization. Conversely, febrile patients (≥ 38&#xa0;°C) and those with CRP ≥ 100&#xa0;mg/L exhibited significantly lower CD73 activity (<i>p</i> = 0.023 and <i>p</i> = 0.004, respectively). CD39 activity was undetectable in 28.2% of patients and showed no association with disease severity or outcome. The lowest CD73 levels were observed in patients requiring oxygen therapy for ≥ 30 days and in those who died before day 7. Serum CD73 activity is associated with hypoxemia and oxygen requirements upon ED admission. Conversely, low CD73 activity reflects a hyperinflammatory state and worse outcomes, supporting its potential use in biomarker-based risk stratification for COVID-19.</p>

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Serum CD73 activity as a biomarker of hypoxemia in COVID-19 patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月26日

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  • Pierrick Le Borgne,
  • Pascal Bilbault,
  • Raphael Clere-Jehl,
  • Julie Favre,
  • François Lefebvre,
  • Geneviève Ubeaud-Séquier,
  • Fatiha El Ghazouani,
  • Julien Demiselle,
  • Florence Toti,
  • Ferhat Meziani,
  • Gilles Kauffenstein

摘要

Ectonucleotidases regulate extracellular purine signaling and play a key role in inflammation and thrombosis, two major components of COVID-19 pathophysiology. We investigated the enzymatic activities of CD39 (NTPDase1) and CD73 (ecto-5’-nucleotidase) as potential biomarkers of disease severity. Patients with RT-PCR-confirmed COVID-19 were enrolled between August 1st, 2020, and August 1st, 2021, and stratified into mild to moderate (MM, n = 55) or severe to critical (SC, n = 30) groups according to WHO criteria. Serum samples were collected on days 1, 3, and 7 following Emergency Department (ED) admission. CD39 and CD73 activities were measured by HPLC using etheno-fluorescent nucleotide substrates and compared to healthy volunteers (HV, n = 30) matched for age and sex. Serum CD73 activity was significantly elevated in COVID-19 patients compared to HV (MM: 76 ± 9.4; SC: 99 ± 21 vs. HV: 25 ± 2.7 pmol/min/µL; p < 0.0001), particularly in patients requiring ≥ 6 L/min oxygen (p = 0.005) or with a respiratory rate > 20/min (p = 0.02). CD73 activity remained elevated throughout hospitalization. Conversely, febrile patients (≥ 38 °C) and those with CRP ≥ 100 mg/L exhibited significantly lower CD73 activity (p = 0.023 and p = 0.004, respectively). CD39 activity was undetectable in 28.2% of patients and showed no association with disease severity or outcome. The lowest CD73 levels were observed in patients requiring oxygen therapy for ≥ 30 days and in those who died before day 7. Serum CD73 activity is associated with hypoxemia and oxygen requirements upon ED admission. Conversely, low CD73 activity reflects a hyperinflammatory state and worse outcomes, supporting its potential use in biomarker-based risk stratification for COVID-19.