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

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

Journal: Biochimica et biophysica acta. Molecular basis of disease 2021;1867(3):166042

PMID: 33338598

Free Full Text on Elsevier Science View on PubMed

Plain Language Summary

Covid-19 infection may alter the immune system, but exactly how is still unclear. A key pathway in the regulation of the immune system is the kynurenine pathway of tryptopham. This observational cohort study aimed to determine how this pathway was affected following infection with Covid-19. The results showed that compared to healthy patients, individuals who tested positive to Covid-19 had an increased ratio of kynurenine:tryptopham and the increase was more pronounced in those who had severe infection and if they were male. It was concluded that the kynurenin:tryptopham ratio could be used as a marker for disease severity and useful for treatments. This study could be used by healthcare professionals to use the kynurenine:tryptopham ratio as a marker for disease severity and stratify patients accordingly for treatments.

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.

Address: Laboratory of Clinical Biochemistry, Mass Spectrometry Unit, Sant'Andrea University Hospital, Rome, Italy.; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY, USA.; Microbiology Unit, Sant'Andrea University Hospital, Rome, Italy; Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy.; Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University, Rome, Italy.; Laboratory of Clinical Biochemistry, Advanced Molecular Diagnostic Unit, Sant'Andrea University Hospital, Rome, Italy.; Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University, Rome, Italy; Laboratory of Clinical Biochemistry, Advanced Molecular Diagnostic Unit, Sant'Andrea University Hospital, Rome, Italy.; University of Lille, Inserm U1172, CHU Lille, Department of Neurology, Stroke Unit, Lille, France.; Department of Mental Health, ASL, Rome 3, Rome, Italy; International Mood & Psychotic Disorders Research Consortium, Mailman Research Center, Belmon, MA, USA.; Sapienza University of Rome, Italy.; Department of Surgical and Medical Science and Translational Medicine, Anesthesia and Intensive Care, Sapienza University, Rome, Italy.; Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy.; Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University, Rome, Italy; Infectious disease Unit, Sant'Andrea University Hospital, Rome, Italy.; Department of Surgical and Medical Science and Translational Medicine, Anesthesia and Intensive Care, Sapienza University, Rome, Italy; Division of Pneumology, Sant'Andrea University Hospital, Rome, Italy.; Emergency Department, Sant'Andrea University Hospital, Rome, Italy.; Department of Physiology and Pharmacology, Sapienza University, Rome, Italy; I.R.C.C.S. Neuromed, Pozzilli, Italy.; Laboratory of Clinical Biochemistry, Mass Spectrometry Unit, Sant'Andrea University Hospital, Rome, Italy; Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University, Rome, Italy; Laboratory of Clinical Biochemistry, Advanced Molecular Diagnostic Unit, Sant'Andrea University Hospital, Rome, Italy.; Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University, Rome, Italy; Laboratory of Clinical Biochemistry, Advanced Molecular Diagnostic Unit, Sant'Andrea University Hospital, Rome, Italy. Electronic address: [email protected].

DOI: 10.1016/j.bbadis.2020.166042