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

Author:

Cysique Lucette A.12,Jakabek David3,Bracken Sophia G.2,Allen‐Davidian Yasmin14,Heng Benjamin56,Chow Sharron5,Dehhaghi Mona56,Staats Pires Ananda5,Darley David R.78,Byrne Anthony78,Phetsouphanh Chansavath9,Kelleher Anthony910,Dore Gregory J.910,Matthews Gail V.910,Guillemin Gilles J.56,Brew Bruce J.137ORCID

Affiliation:

1. Peter Duncan Neuroscience Research Unit St. Vincent's Centre for Applied Medical Research Darlinghurst New South Wales Australia

2. School of Psychology UNSW Sydney New South Wales Australia

3. Neurology Department St. Vincent's Hospital Darlinghurst New South Wales Australia

4. School of Psychology Macquarie University Sydney New South Wales Australia

5. Macquarie Medical School Macquarie University Sydney New South Wales Australia

6. PANDIS.org Sydney New South Wales Australia

7. Faculty of Medicine UNSW Sydney New South Wales Australia

8. Respiratory Medicine Department St. Vincent's Hospital Darlinghurst New South Wales Australia

9. Kirby Institute UNSW Sydney New South Wales Australia

10. Infectious Disease and Immunology Department St. Vincent's Hospital Darlinghurst New South Wales Australia

Abstract

AbstractObjectiveTo 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.

Funder

National Health and Medical Research Council

Publisher

Wiley

Subject

Neurology (clinical),General Neuroscience

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