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

Autor: Cysique LA; Peter Duncan Neuroscience Research Unit, St. Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia.; School of Psychology, UNSW, Sydney, New South Wales, Australia., Jakabek D; Neurology Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia., Bracken SG; School of Psychology, UNSW, Sydney, New South Wales, Australia., Allen-Davidian Y; Peter Duncan Neuroscience Research Unit, St. Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia.; School of Psychology, Macquarie University, Sydney, New South Wales, Australia., Heng B; Macquarie Medical School, Macquarie University, Sydney, New South Wales, Australia.; PANDIS.org, Sydney, New South Wales, Australia., Chow S; Macquarie Medical School, Macquarie University, Sydney, New South Wales, Australia., Dehhaghi M; Macquarie Medical School, Macquarie University, Sydney, New South Wales, Australia.; PANDIS.org, Sydney, New South Wales, Australia., Staats Pires A; Macquarie Medical School, Macquarie University, Sydney, New South Wales, Australia., Darley DR; Faculty of Medicine, UNSW, Sydney, New South Wales, Australia.; Respiratory Medicine Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia., Byrne A; Faculty of Medicine, UNSW, Sydney, New South Wales, Australia.; Respiratory Medicine Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia., Phetsouphanh C; Kirby Institute, UNSW, Sydney, New South Wales, Australia., Kelleher A; Kirby Institute, UNSW, Sydney, New South Wales, Australia.; Infectious Disease and Immunology Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia., Dore GJ; Kirby Institute, UNSW, Sydney, New South Wales, Australia.; Infectious Disease and Immunology Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia., Matthews GV; Kirby Institute, UNSW, Sydney, New South Wales, Australia.; Infectious Disease and Immunology Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia., Guillemin GJ; Macquarie Medical School, Macquarie University, Sydney, New South Wales, Australia.; PANDIS.org, Sydney, New South Wales, Australia., Brew BJ; Peter Duncan Neuroscience Research Unit, St. Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia.; Neurology Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia.; Faculty of Medicine, UNSW, Sydney, New South Wales, Australia.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2023 Aug; Vol. 10 (8), pp. 1338-1352. Date of Electronic Publication: 2023 Jun 15.
DOI: 10.1002/acn3.51825
Abstrakt: Objective: To 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.
Methods: A 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.
Results: Across 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).
Interpretation: The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC, thereby enabling biomarker and therapeutic possibilities.
(© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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