Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study.

Luana Lionetto, Martina Ulivieri, Matilde Capi, Donatella De Bernardini, Francesco Fazio, Andrea Petrucca, Leda Marina Pomes, Ottavia De Luca, Giovanna Gentile, Barbara Casolla, Martina Curto, Gerardo Salerno, Serena Schillizzi, Maria Simona Torre, Iolanda Santino, Monica Rocco, Paolo Marchetti, Antonio Aceti, Alberto Ricci, Rita BonfiniFerdinando Nicoletti, Maurizio Simmaco, Marina Borro

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention.

Original languageEnglish (US)
Article number166042
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1867
Issue number3
DOIs
StatePublished - Mar 1 2021
Externally publishedYes

Keywords

  • Kynurenine pathway
  • Kynurenine:Tryptophan ratio
  • SARS-CoV2
  • Severity of infection

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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