The kynurenine pathway relates to post‐acute COVID‐19 objective cognitive impairment and PASC

Abstract

ObjectiveTo determine the prevalence and natural history of post‐acute COVID‐19 objective cognitive impairment and function, and their relationship to demographic, clinical factors, post‐acute sequelae of COVID‐19 (PASC), and biomarkers.MethodsA total of 128 post‐acute COVID‐19 patients (age = 46 ± 15; 42% women, acute disease severity: not hospitalized: 38.6% mild: 0–1 symptoms, 52% 2+ symptoms; 9.4% hospitalized) completed standard cognition, olfaction, and mental health examinations 2‐, 4‐, and 12‐month post diagnosis. Over the same time frame, WHO‐defined PASC was determined. Blood cytokines, peripheral neurobiomarkers, and kynurenine pathway (KP) metabolites were measured. Objective cognitive function was demographically/practice corrected, and impairment prevalence was determined using the evidence‐based Global Deficit Score method to detect at least mild cognitive impairment (GDS > 0.5). Linear mixed effect regression models with time effect (month post diagnosis) evaluated the relationships to cognition.ResultsAcross the 12‐month study period, mild to moderate cognitive impairment ranged from 16% to 26%, and 46.5% were impaired at least once. Impairment associated with poorer work capacity (p < 0.05), and 2‐month objectively tested anosmia (p < 0.05). PASC with (p = 0.01) and without disability (p < 0.03) associated with acute COVID‐19 severity. KP measures showed prolonged activation (2 to 8 months) (p < 0.0001) linked to IFN‐beta in those with PASC. Of the blood analytes, only the KP metabolites (elevated quinolinic acid, 3‐hydroxyanthranilic acid, kynurenine, the kynurenine/tryptophan ratio) associated (p < 0.001) with poorer cognitive performance and greater likelihood of impairment. PASC, independent of disability associated with abnormal kynurenine/tryptophan (p < 0.03).InterpretationThe kynurenine pathway relates to post‐acute COVID‐19 objective cognitive impairment and PASC, thereby enabling biomarker and therapeutic possibilities.

Resistance training's impact on blood biomarkers and cognitive function in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial

“…Finally, we found that post-intervention KYN levels were significantly higher in older adults with high MCI risk compared to older adults with low MCI risk. Consistent with our finding, cognitive impairment has been associated with higher KYN levels in individuals with type 2 diabetes mellitus [ 47 ] and acute post COVID-19 individuals [ 48 ]. KYN levels increase in case of elevated pro-inflammatory cytokine concentrations, which stimulates its conversion from tryptophan by indoleamine-2,3-dioxygenase [ 49 ].…”

Effects of COVID-19 on cognition and brain health

“…Despite these associations, the nature of such observational studies means that it is difficult to establish causal, directional relationships between depression and cognitive function. Further, there is evidence that post-acute COVID-19 cognitive impairment can occur regardless of mental health symptoms in all acute severity groups [ 34 , 36 , 66 ]. This is consistent with findings from electronic health records: mental health symptoms such as anxiety and depression returned to normal within 2 months, but cognitive symptoms increased for at least 2 years [ 6 ].…”

Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection

“…The difference in these outcomes needs further exploration, including qualitative evaluation, but suggests that the lived experience and recovery of LC is likely to be complex and multifactorial. Irrespective of immunological recovery, other causes of poor health, including persisting organ damage, cognitive impairment 28 , and the mental health impact of significant illness, may be contributing and mean that full physical recovery may lag behind immune recovery.…”