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

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.

Is there a 'zone of eye contact' within the borders of the face?

Eye contact is a salient feature of everyday interactions, yet it is not obvious what the physical conditions are under which we feel that we have eye contact with another person. Here we measure the range of locations that gaze can fall on a person's face to elicit a sense of eye contact. Participants made judgements about eye contact while viewing rendered images of faces with finely-varying gaze direction at a close interpersonal distance (50 cm). The 'zone of eye contact' tends to peak between the two eyes and is often surprisingly narrower than the observer's actual eye region. Indeed, the zone tends to extend further across the face in height than in width. This shares an interesting parallel with the 'cyclopean eye' of visual perspective - our sense of looking out from a single point in space despite the physical separation of our two eyes. The distribution of eye-contact strength across the face can be modelled at the individual-subject level as a 2D Gaussian function. Perception of eye contact is more precise than the sense of having one's face looked at, which captures a wider range of gaze locations in both the horizontal and vertical dimensions, at least at the close viewing distance used in the present study. These features of eye-contact perception are very similar cross-culturally, tested here in Australian and Japanese university students. However, the shape and position of the zone of eye contact does vary depending on recent sensory experience: adaptation to faces with averted gaze causes a pronounced shift and widening of the zone across the face, and judgements about eye contact also show a positive serial dependence. Together, these results provide insight into the conditions under which eye contact is felt, with respect to face morphology, culture, and sensory context.