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Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study

Cysique, L. A.; Jakabek, D.; Bracken, S. G.; Allen-Davidian, Y.; Heng, B.; Chow, S.; Dehhaghi, M.; Staats-Pires, A.; Darley, D. R.; Byrne, A.; Phetsouphanh, C.; Kelleher, A.; Dore, G.; Matthews, G. V.; Guillemin, G.; Brew, B. J.

2022-06-07 infectious diseases
10.1101/2022.06.07.22276020 medRxiv
Show abstract

Cognitive impairment and function post-acute mild to moderate COVID-19 are poorly understood. We report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung function, physical and mental health were assessed at 2-month post diagnosis. Blood cytokines, neuro-biomarkers, and kynurenine pathway (KP) metabolites were measured at 2-, 4-, 8- and 12- months. Mild to moderate cognitive impairment (demographically corrected) was present in 16%, 23%, and 26%, at 2-, 4- and 12-months post diagnosis, respectively. Overall cognitive performance mildly, but significantly (p<.001) declined. Cognitive impairment was more common in those with anosmia (p=.05), but only at 2 months. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly (p<.001) associated with cognitive decline. The KP as a unique biomarker offers a potential therapeutic target for COVID-19-related cognitive impairment.

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