The Impact of Cognitive Function on Health-Related Quality of Life in Persons with Post-COVID-19 Condition: A Randomized Controlled Trial on Vortioxetine (preprint)

ABSTRACT

Background Post-Covid-19 Condition (PCC) manifests in persistent, debilitating symptoms that affect multiple cognitive domains. These symptoms can negatively impact an affected individual's health-related quality of life (HRQoL). Herein, we investigate the effects of cognitive function on HRQoL in persons with PCC. Secondarily, we determine whether vortioxetine modulates cognitive function on HRQoL. Methods Participants aged 18-65 years were randomized to receive vortioxetine or placebo for 8 weeks. HRQoL was measured using the World Health organization Wellbeing Scale 5-item, cognition was measured using the Digit Symbol Substitution Test and the Trail-Making Test A/B. Generalized estimating equations were used to model the relationship of cognition to HRQoL for each treatment group. Results 147 participants, 75.5% of which were female, were included in the analysis. At baseline, there was a statistically significant positive association between WHO-5 scores and combined DSST z-scores (beta; = 0.090, 95% CI [0.051, 0.129], p < 0.001), and a statistically significant negative association with TMT-A (beta; = -0.007, 95% CI [-0.011, -0.003], p < 0.001) and -B (beta; = -0.002, 95% CI [-0.003, 0.000], p = 0.024) scores, respectively. A significant treatment, time, and combined DSST z-score interaction on changes in overall WHO-5 total score (x2 = 15.481, p = 0.004) was reported. After adjusting for the type of cognitive test, there was a significant between-group difference (mean change = 1.77, SEM = 0.868, p = 0.042) favoring vortioxetine. Conclusion Cognitive function is significantly associated with HRQoL in persons with PCC where enhanced cognitive functioning is associated with a better HRQoL. Vortioxetine is effective in improving HRQoL through enhancing cognitive function. Cognitive function in persons with PCC provides the impetus for future therapeutic targets for persons with PCC. Future studies should aim to investigate pro-cognitive therapeutic strategies.