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Meta-Analysis
. 2022 Jul 15;22(1):615.
doi: 10.1186/s12879-022-07582-1.

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

Abbas F Almulla  1   2 , Thitiporn Supasitthumrong  3 , Chavit Tunvirachaisakul  3 , Ali Abbas Abo Algon  4 , Hussein K Al-Hakeim  5 , Michael Maes  3   6   7
Affiliations
Meta-Analysis

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

Abbas F Almulla et al. BMC Infect Dis. .

Abstract

Background: Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both induce indoleamine-2,3-dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim of this study was to systematically review and meta-analyze the status of the TRYCAT pathway, including the levels of TRP and kynurenine (KYN) and the activity of IDO, as measured by the ratio of KYN/TRP.

Methods: This systematic review searched PubMed, Google Scholar, and Web of Sciences and included 14 articles that compared TRP and tryptophan catabolites (TRYCATs) in COVID-19 patients versus non-COVID-19 controls, as well as severe/critical versus mild/moderate COVID-19. The analysis was done on a total of 1269 people, including 794 COVID-19 patients and 475 controls.

Results: The results show a significant (p < 0.0001) increase in the KYN/TRP ratio (standardized mean difference, SMD = 1.099, 95% confidence interval, CI: 0.714; 1.484) and KYN (SMD = 1.123, 95% CI: 0.730; 1.516) and significantly lower TRP (SMD = - 1.002, 95%CI: - 1.738; - 0.266) in COVID-19 versus controls. The KYN/TRP ratio (SMD = 0.945, 95%CI: 0.629; 1.262) and KYN (SMD = 0.806, 95%CI: 0.462; 1.149) were also significantly (p < 0.0001) higher and TRP lower (SMD = - 0.909, 95% CI: - 1.569; - 0.249) in severe/critical versus mild/moderate COVID-19. No significant difference was detected in kynurenic acid (KA) and the KA/KYN ratio between COVID-19 patients and controls.

Conclusions: Our results indicate increased activity of the IDO enzyme in COVID-19 and severe/critical patients. The TRYCAT pathway is implicated in the pathophysiology and progression of COVID-19 and may signal a worsening outcome of the disease.

Keywords: COVID-19; Inflammation; Oxidative stress; SARS-Cov-2; Tryptophan catabolites.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Summary of TRYCAT pathway in COVID-19. BMI body mass index, C cohort, T2DM type 2 diabetes mellitus, IFN-γ interferon-Gamma, IL-6 interleukin 6, IL-1β interleukin-1 beta, O&NS oxidative and nitrosative stress, O2 oxygen, CCTA chest computed tomography abnormalities, AhR aryl hydrocarbon receptor, IDO indoleamine 2,3 dioxygenase, TDO tryptophan 2,3-dioxygenase, KAT kynurenine aminotransferase, KMO kynurenine 3-monooxygenase, KYNU kynureninase, TRP tryptophan, KYN kynurenine, KA kynurenic acid, 3HK 3-hydroxykynurenine, AA anthranilic acid, XA xanthurenic acid, 3HA 3-hydroxyanthranilic acid, PA picolinic acid, QA quinolinic acid, NAD +  nicotinamide adenine dinucleotide. Created with BioRender.com
Fig. 2
Fig. 2
Prisma flow chart
Fig. 3
Fig. 3
Forest plot with the results of a meta-analysis performed on the kynurenine/tryptophan (KYN/TRP) ratio in COVID-19 patients versus non-COVID-19 controls
Fig. 4
Fig. 4
Forest plot with the results of a meta-analysis performed on the kynurenine/tryptophan (KYN/TRP) ratio in severe/critical COVID-19 versus mild/moderate COVID-19
See this image and copyright information in PMC

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