RESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon-γ (IFN-γ), interferon-ß (IFN-ß), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.
RESUMEN
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, complex, and highly debilitating long-term illness. People with ME/CFS are typically unable to carry out their routine activities. Key hallmarks of the disease are neurological and gastrointestinal impairments accompanied by pervasive malaise that is exacerbated after physical and/or mental activity. Currently, there is no validated cure of biomarker signature for this illness. Impaired tryptophan (TRYP) metabolism is thought to play significant role in the pathobiology of ME/CFS. TRYP is an important precursor for serotonin and the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+). TRYP has been associated with the development of some parts of the brain responsible for behavioural functions. The main catabolic route for TRYP is the kynurenine pathway (KP). The KP produces NAD+ and several neuroactive metabolites with neuroprotective (i.e., kynurenic acid (KYNA)) and neurotoxic (i.e., quinolinic acid (QUIN)) activities. Hyperactivation of the KP, whether compensatory or a driving mechanism of degeneration can limit the availability of NAD+ and exacerbate the symptoms of ME/CFS. This review discusses the potential association of altered KP metabolism in ME/CFS. The review also evaluates the role of the patient's gut microbiota on TRYP availability and KP activation. We propose that strategies aimed at raising the levels of NAD+ (e.g., using nicotinamide mononucleotide and nicotinamide riboside) may be a promising intervention to overcome symptoms of fatigue and to improve the quality of life in patients with ME/CFS. Future clinical trials should further assess the potential benefits of NAD+ supplements for reducing some of the clinical features of ME/CFS.