Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months

Abstract

Background: Fatigue is a frequent and one of the most debilitating symptoms in post-COVID syndrome (PCS). Recently, we proposed that fatigue is caused by hypoactivity of the brain's arousal network and reflected by a reduction of cognitive processing speed. However, it is unclear whether cognitive slowing is revealed by standard neuropsychological tests, represents a selective deficit, and how it develops over time.

Objectives: This prospective study assesses whether PCS patients show deficits particularly in tests relying on processing speed and provides the first longitudinal assessment focusing on processing speed in PCS patients.

Methods: Eighty-eight PCS patients with cognitive complaints and 50 matched healthy controls underwent neuropsychological assessment. Seventy-seven patients were subsequently assessed at 6-month follow-up. The Test for Attentional Performance measured tonic alertness as primary study outcome and additional attentional functions. The Neuropsychological Assessment Battery evaluated all key cognitive domains.

Results: Patients showed cognitive slowing indicated by longer reaction times compared to control participants (r = 0.51, p < 0.001) in a simple-response tonic alertness task and in all more complex tasks requiring speeded performance. Reduced alertness correlated with higher fatigue (r = - 0.408, p < 0.001). Alertness dysfunction remained unchanged at 6-month follow-up (p = 0.240) and the same was true for most attention tasks and cognitive domains.

Conclusion: Hypoarousal is a core deficit in PCS which becomes evident as a selective decrease of processing speed observed in standard neuropsychological tests. This core deficit persists without any signs of amelioration over a 6-month period of time.

Keywords: Cognitive dysfunction; Fatigue; Longitudinal course; Post-COVID; Processing speed; Tonic alertness.

Fig. 1

Study flow: 88 PCS patients and 50 sociodemographically matched healthy control participants were assessed with neuropsychological tests during the period from January 21, 2021 to September 27, 2022 at the Neuro-Post-COVID-Centre of the Department of Neurology of Jena University Hospital. Seventy-seven PCS patients returned for the 6-month follow-up assessment

Fig. 2

Violin plots of distributions, medians (line) and means (point) of T-scores of performance in the subtests of the Test for Attentional Performance (TAP) for healthy control participants (blue) and PCS patients at baseline (light red) and at 6-month follow-up (dark red). T-scores: M = 50, SD = 10. P values of comparisons between PCS patients and healthy control participants and between baseline and 6-month follow-up assessment within the PCS patient group

Fig. 3

Violin plots of distributions, medians (line) and means (point) of standard scores of performance in the Neuropsychological Assessment Battery Screening (S-NAB) for healthy control participants (blue) and PCS patients at baseline (light red) and at 6-month follow-up (dark red). Standard scores: M = 100, SD = 15. P values of comparisons between PCS patients and healthy control participants and between baseline and 6-month follow-up assessment within the PCS patient group

Fig. 4

Heat map depicting the strength of Pearson/point-biserial correlations between neurocognitive performance (with higher values in standardized scores relating to better performance) and self-rated fatigue, self-rated depressive symptoms, hospitalization, time from SARS-CoV-2 infection, body mass index, nicotine use, comorbidities, sex, age, education, and occupational status within the PCS patient group at baseline assessment. RT reaction times

Fig. 5

Heat map depicting the strength of Pearson correlations between neurocognitive performance at baseline and at 6-month follow-up within the PCS patient group. RT reaction times