Over a year ago, in our first issue Newsletter, we highlighted the importance of the kynurenine pathway (KP) in COVID-19 and asked if KP alteration in people with COVID-19 may lead to neurodegeneration (see our Newsletter issue 1 to recap). Fast track to the present, some interesting insights into that question have emerged and are covered in this month’s feature article.
Giron et al focus on a subset of individuals who experience persistent, recurrent, or new symptoms following COVID-19 acute infection, commonly referred to as long COVID (see WHO) in comparison to those without long COVID. They examined the symptoms, quality of life, and overall health status together with plasma markers of inflammation and metabolites using untargeted metabolomics.
Given the known KP alterations in people with SARS-CoV-2 infection, not surprisingly, this study found that those with long COVID have higher quinolinic acid (QA) levels compared to those without long COVID. Individuals with long COVID who presented with neuropathy showed the highest Kyn/Trp ratio compared to those without neuropathy and long COVID. Interestingly, the long COVID group with neuropathy also showed a higher QA/TRP ratio when compared to those without long COVID. Further, these KP ratios had a moderately strong correlation with several pro-inflammatory markers. The study also extends their findings to evidence of fungal (translocation) marker and NF-kB signaling, which we know are associated with alteration in the KP activity.
Taken together, this suggests that inflammation may drive the activation of the KP, altering the overproduction of QA to drive excitotoxicity-induced neurodegeneration. Moreover, the association between higher QA/TRP ratio and poorer overall health scores in the long COVID group implies the potential role of targeting glutamatergic modulation for a better outcome for long COVID.