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

Chilosi, Marco; Doglioni, Claudio; Ravaglia, Claudia; Martignoni, Guido; Salvagno, Gian Luca; Pizzolo, Giovanni; Bronte, Vincenzo; Poletti, Venerino

doi:10.3390/biomedicines10061332

Cited by 10 publications

(8 citation statements)

References 297 publications

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“…28 Because the metabolites kynurenine and kynurenine acid are agonists of the AHR receptor, there is a 'runaway positive feedback loop' producing more and more metabolites. 28,[30][31][32]…”

Section: Discussionmentioning

confidence: 99%

“…The KP is stimulated by inflammation and in PCS it is found overactive. [26][27][28]30,32 [Figure 6 here]…”

Section: Dysregulation Of the Tryptophan Systemmentioning

confidence: 99%

“…Research shows that the amount of tryptophan in blood is decreased in PCS patients. [30][31][32] Tryptophan deficiency is probably already present during the infection with Covid-19, because Covid-19 attaches with its spike proteins to the Angiotensin Converting Enzyme (ACE2) receptors in the intestines, while tryptophan also uses the same receptor to be absorbed from the intestines. 54 There is a significant relationship between the level of metabolites in blood and the severity of cognitive impairment in PCS, 28 (p < 0.001).…”

Section: Dysregulation Of the Tryptophan Systemmentioning

confidence: 99%

“…Both the serotonin pathway and the KP use the same precursor tryptophan, an essential amino acid. In the event of a deficiency of this precursor, which is the case with PCS, [30][31][32] the serotonin pathway activated by SSRIs could be regarded as a competitor of the KP. (See Figure 6 in section 'Potential mechanisms of action of SSRIs).…”

Section: Introductionmentioning

confidence: 99%

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Treatment of 95 post-Covid patients with SSRIs

Rus,

de Vries,

de Vries

et al. 2023

Preprint

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After Covid-19 infection, 12.5% develops post-Covid-syndrome (PCS). Symptoms indicate numerous affected organ systems. After a year, chronic fatigue, dysautonomia and neurological and neuropsychiatric complaints predominate. In this study, 95 PCS patients were treated with selective serotonin reuptake inhibitors (SSRIs). This study used an exploratory questionnaire and found that two-thirds of patients had a reasonably good to strong response on SSRIs, over a quarter of patients had moderate response, while 10% reported no response. Overall, patients experienced substantial improved well-being. Brainfog and sensory overload decreased most, followed by chronic fatigue and dysautonomia. Outcomes were measured with three different measures that correlated strongly with each other. The response to SSRIs in PCS conditions was explained by seven possible neurobiological mechanisms based on recent literature on PCS integrated with already existing knowledge. Important for understanding these mechanisms is the underlying biochemical interaction between various neurotransmitter systems and parts of the immune system, and their dysregulation in PCS. The main link appears to be with the metabolic kynurenine pathway (KP) which interacts extensively with the immune system. The KP uses the same precursor as serotonin: tryptophan. The KP is overactive in PCS which maintains inflammation and which causes a lack of tryptophan. Finally, potential avenues for future research to advance this line of clinical research are discussed.

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Section: Discussionmentioning

confidence: 99%

“…The KP is stimulated by inflammation and in PCS it is found overactive. [26][27][28]30,32 [Figure 6 here]…”

Section: Dysregulation Of the Tryptophan Systemmentioning

confidence: 99%

Section: Dysregulation Of the Tryptophan Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Treatment of 95 post-Covid patients with SSRIs

Rus,

de Vries,

de Vries

et al. 2023

Preprint

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“…50,51 In this context, our data suggest that a KD may improve patient health with reduced risk of hospitalization and long covid. 52,53 On the contrary, a diet rich in carbohydrates may exacerbate the inflammatory response during infection.…”

Section: Discussionmentioning

confidence: 99%

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

Palermo¹,

Shen²,

Hoeve

et al. 2022

Preprint

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The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic anti-inflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism.

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