Inflammation control and improvement of cognitive function in COVID-19 infections: is there a role for kynurenine 3-monooxygenase inhibition?

Collier, Mary E.W.; Zhang, Shaowei; Scrutton, Nigel S.; Giorgini, Flaviano

doi:10.1016/j.drudis.2021.02.009

Cited by 27 publications

(28 citation statements)

References 83 publications

(115 reference statements)

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“…The alteration of TKP by increasing the transformation of TRP to KYN has been shown to reduce serotonin levels in post-COVID-19 patients (Thomas et al 2020 ). Even though depression and anxiety disorders are reported to be sensitive in post-COVID-19 patients (Mazza et al 2020 ), whether the vulnerability of psychiatric symptoms in these patients is associated with decreased serotonin due to increased TRP to KYN conversion remains to be determined (Collier et al 2021 ). We believe that the current study is significant in terms of revealing the link between TKP and depression/anxiety/stress.…”

Section: Discussionmentioning

confidence: 99%

Psychological outcomes of COVID-19 survivors at sixth months after diagnose: the role of kynurenine pathway metabolites in depression, anxiety, and stress

et al. 2022

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Coronavirus disease 2019 (COVID-19) has resulted in long-term psychiatric symptoms because of the immunologic response to the virus itself as well as fundamental life changes related to the pandemic. This immune response leads to altered tryptophan (TRP)–kynurenine (KYN) pathway (TKP) metabolism, which plays an essential role in the pathophysiology of mental illnesses. We aimed to define TKP changes as a potential underlying mechanism of psychiatric disorders in post-COVID-19 patients. We measured plasma levels of several TKP markers, including KYN, TRP, kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), as well as the TRP/KYN, KYNA/3-HK, and KYNA/QUIN ratios, in 90 post-COVID-19 patients (on the first day of hospitalization) and 59 healthy controls (on the first admission to the Check-Up Center). An online questionnaire that included the Depression, Anxiety and Stress Scale-21 (DASS-21) was used 6 months after the initial assessment in both groups. A total of 32.2% of participants with COVID-19 showed depressive symptoms, 21.1% exhibited anxiety, and 33.3% had signs of stress at follow-up, while 6.6% of healthy controls exhibited depressive and anxiety symptoms and 18.6% had signs of stress. TRP and 3-HK were negative predictors of anxiety and stress, but KYN positively predicted anxiety and stress. Moreover, TRP negatively predicted depression, while KYNA/3-HK was a negative predictor of anxiety. The correlation between depression, anxiety, and stress and TKP activation in COVID-19 could provide prospective biomarkers, especially the reduction in TRP and 3HK levels and the increase in KYN. Our results suggest that the alteration of TKP is not only a potential biomarker of viral infection-related long-term psychiatric disorders but also that the therapy targets future viral infections related to depression and anxiety. Supplementary Information The online version contains supplementary material available at 10.1007/s00702-022-02525-1.

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Section: Discussionmentioning

confidence: 99%

Psychological outcomes of COVID-19 survivors at sixth months after diagnose: the role of kynurenine pathway metabolites in depression, anxiety, and stress

et al. 2022

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“…Kynurenine as a positive correlate of CRP is expected since it is involved in inflammation and immune activation in various disease contexts 125,126 . Additionally, within COVID-19, kynurenine has been found to be positively correlated with proinflammatory cytokines 127,128 , and the kynurenine pathway seems to be activated in COVID-19 patients 129 .…”

Section: C-reactive Protein (Crp)mentioning

confidence: 95%

Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

Rahnavard

Mann

Giri

et al. 2021

Preprint

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Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19.

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“…In COVID-19 and PACS, several neurological complications can be observed, from isolated anosmia and/or dysgeusia to severe neuropsychiatric conditions, and the activation of TKP has been proposed as a mechanistic explanation and a promising therapeutic target [ 134 , 135 , 136 , 137 , 138 , 139 , 140 ]. In fact, the persistence of an abnormal K/T ratio and tryptophan decrease as well as vascular abnormalities occur in a number of patients and might be considered a feature of PACS [ 141 , 142 , 143 ].…”

Section: Introductionmentioning

confidence: 99%

Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia

et al. 2022

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Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review. Recent histological studies have documented that, in COVID-19 patients, indoleamine 2,3-dioxygenase (IDO) enzymes are differentially expressed in the pulmonary blood vessels, i.e., IDO1 prevails in early/mild pneumonia and in lung tissues from patients suffering from long COVID-19, whereas IDO2 is predominant in severe/fatal cases. We hypothesize that IDO1 is necessary for a correct control of the vascular tone of pulmonary vessels, and its deficiency in COVID-19 might be related to the syndrome’s evolution toward vascular dysfunction. The complexity of this scenario is discussed in light of possible therapeutic manipulations of the tryptophan/kynurenine pathway in COVID-19 and post-acute COVID-19 syndromes.

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Inflammation control and improvement of cognitive function in COVID-19 infections: is there a role for kynurenine 3-monooxygenase inhibition?

Cited by 27 publications

References 83 publications

Psychological outcomes of COVID-19 survivors at sixth months after diagnose: the role of kynurenine pathway metabolites in depression, anxiety, and stress

Psychological outcomes of COVID-19 survivors at sixth months after diagnose: the role of kynurenine pathway metabolites in depression, anxiety, and stress

Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia

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