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 (β = 0.090, 95% CI [0.051, 0.129], p < 0.001), and a statistically significant negative association with TMT-A (β = −0.007, 95% CI [-0.011, −0.003], p < 0.001) and -B (β = −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 (χ2 = 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.

Dr. Roger S. McIntyre has received research grant support from CIHR, GACD, National Natural Science Foundation of China (NSFC), and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Kayla M. Teopiz has received fees from Braxia Scientific Corp. Dr. Joshua D. Rosenblat has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services Inc (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Janssen, Allergan, Lundbeck, Sunovion and COMPASS

NCT05047952

The primary clinical trial was sponsored by the Brain and Cognition Discovery Foundation (BCDF) through an unrestricted research grant from H. Lundbeck A/S, Copenhagen, Denmark. BCDF functions as a non-profit research organization. No specific grant from public, commercial, or not-for-profit funding organizations was given to the authors of this post hoc analysis.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The methodology, and data for this study, are sourced from a primary study that is now published (ClinicalTrials.gov number, NCT05047952). Advarra, a local research ethics board (REB) that complies with Health Canada regulations, approved the research design of this paper (IRB #00000971).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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↵† denotes co-first authorship

angela.kwanmail.utoronto.ca

mlakh088uottawa.ca

hanny.lemail.utoronto.ca

gsingh93student.ubc.ca

kayla.teopizmail.utoronto.ca

ziji.guomail.utoronto.ca

amankustudent.ubc.ca

joshua.rosenblatuhn.ca

roger.mcintyrebcdf.org

The data and research materials that support the findings of this study are available from the corresponding author, R.S.M, upon reasonable request and will be anonymized.