TY - JOUR
T1 - Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2
T2 - An observational cohort study.
AU - Lionetto, Luana
AU - Ulivieri, Martina
AU - Capi, Matilde
AU - De Bernardini, Donatella
AU - Fazio, Francesco
AU - Petrucca, Andrea
AU - Pomes, Leda Marina
AU - De Luca, Ottavia
AU - Gentile, Giovanna
AU - Casolla, Barbara
AU - Curto, Martina
AU - Salerno, Gerardo
AU - Schillizzi, Serena
AU - Torre, Maria Simona
AU - Santino, Iolanda
AU - Rocco, Monica
AU - Marchetti, Paolo
AU - Aceti, Antonio
AU - Ricci, Alberto
AU - Bonfini, Rita
AU - Nicoletti, Ferdinando
AU - Simmaco, Maurizio
AU - Borro, Marina
N1 - Publisher Copyright:
© 2020
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
KW - Kynurenine pathway
KW - Kynurenine:Tryptophan ratio
KW - SARS-CoV2
KW - Severity of infection
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U2 - 10.1016/j.bbadis.2020.166042
DO - 10.1016/j.bbadis.2020.166042
M3 - Article
AN - SCOPUS:85098602573
SN - 0925-4439
VL - 1867
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 3
M1 - 166042
ER -