Tag: tryptophan depletion

Persistent immune dysregulation and metabolic alterations following SARS-CoV-2 infection

Abstract:

SARS-CoV-2 can cause a variety of post-acute sequelae including Long COVID19 (LC), a complex, multisystem disease characterized by a broad range of symptoms including fatigue, cognitive impairment, and post-exertional malaise. The pathogenesis of LC is incompletely understood.

In this study, we performed comprehensive cellular and transcriptional immunometabolic profiling within a cohort that included SARS-CoV-2-naïve controls (NC, N=30) and individuals with prior COVID-19 (~4-months) who fully recovered (RC, N=38) or went on to experience Long COVID symptoms (N=58).

Compared to the naïve controls, those with prior COVID-19 demonstrated profound metabolic and immune alterations at the proteomic, cellular, and epigenetic level. Specifically, there was an enrichment in immature monocytes with sustained inflammasome activation and oxidative stress, elevated arachidonic acid levels, decreased tryptophan, and variation in the frequency and phenotype of peripheral T-cells. Those with LC had increased CD8 T-cell senescence and a distinct transcriptional profile within CD4 and CD8 T-cells and monocytes by single cell RNA sequencing. Our findings support a profound and persistent immunometabolic dysfunction that follows SARS-CoV-2 which may form the pathophysiologic substrate for LC.

Our findings suggest that trials of therapeutics that help restore immune and metabolic homeostasis may be warranted to prevent, reduce, or resolve LC symptoms.

Source: Lage SL, Bricker-Holt K, Rocco JM, Rupert A, Donovan FX, Abramzon YA, Chandrasekharappa SC, McNinch C, Cook L, Amaral EP, Rosenfeld G, Dalhuisen T, Eun A, Hoh R, Fehrman E, Martin JN, Deeks SG, Henrich TJ, Peluso MJ, Sereti I. Persistent immune dysregulation and metabolic alterations following SARS-CoV-2 infection. medRxiv [Preprint]. 2025 Apr 17:2025.04.16.25325949. doi: 10.1101/2025.04.16.25325949. PMID: 40321289; PMCID: PMC12047922. https://pmc.ncbi.nlm.nih.gov/articles/PMC12047922/ (Full text)

Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS.

Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS. In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo.To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion.

FINDINGS: Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states. ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition.

CONCLUSIONS: These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS.

TRIAL REGISTRATION: ISRCTN07518149.

 

Source: The GK, Verkes RJ, Fekkes D, Bleijenberg G, van der Meer JW, Buitelaar JK. Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study. BMC Res Notes. 2014 Sep 16;7:650. doi: 10.1186/1756-0500-7-650. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176591/ (Full article)