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Background: Individuals who have recovered from the acute stage of SARS-CoV-2 infection may be at risk of developing post-COVID-19 condition (PCC), characterised by a spectrum of persisting, non-specific, and functionally impairing symptoms across multiple organ systems. Obesity has been implicated as a risk factor for PCC, mediated by chronic systemic inflammation. The foregoing has also been separately reported to mediate cognitive dysfunction in PCC. Methods: This is a post-hoc analysis of a randomised, double-blinded, placebo-controlled clinical trial evaluating vortioxetine treatment for cognitive impairments in persons with PCC who received vortioxetine or placebo for eight weeks. This analysis comprises baseline data, examining the impact of BMI on cognitive functioning measured by the Digit Symbol Substitution Test (DSST) and Trails Making Tests (TMT)-A/B, as well as inflammation, via serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results: Complete data from 70 participants were statistically analysed and adjusted for age and sex. BMI was negatively correlated with performance on the DSST (β = −0.003, p = 0.047), TMT-A (β = −0.006, p = 0.025), and TMT-B (β = −0.006, p = 0.002). BMI was positively correlated with serum CRP (unstandardized β = 0.193, standardized β = 0.612, p < 0.001) and ESR (β = 0.039, p < 0.001) levels. Conclusion: We observed a significant negative correlation between BMI and cognitive functioning, and a significant positive correlation between BMI and inflammation in persons with PCC, suggesting a bidirectional interplay between BMI, PCC, and cognitive function; individuals with an elevated BMI may be at a greater risk of developing PCC and/or presenting with greater cognitive deficits mediated by chronic systemic inflammation. [ABSTRACT FROM AUTHOR]

Post-COVID-19 condition (PCC), also known as "long COVID," is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC. Anhedonia (i.e. reduced capacity for pleasure) and compromised psychosocial functioning are notable symptoms in those with PCC. We aimed to provide insights to understand the effects of anhedonia and impaired psychosocial functioning of individuals with PCC. This post-hoc analysis used data from an 8-week, double-blind, randomized, placebo-controlled trial which evaluated vortioxetine for cognitive deficits in individuals with PCC (Clinicaltrials.gov Identifier: NCT05047952). A total of 147 eligible participants were randomly assigned to receive vortioxetine or matching placebo over eight weeks of double-blind treatment. Our study investigated the relationship between anhedonia, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS), and psychosocial functioning, measured with the Post-COVID Functional Status (PCFS) scale. The analysis was conducted using a generalized linear model, with adjustments for relevant covariates such as age, sex, education, suspected versus confirmed COVID diagnosis, MDD diagnosis, and alcohol consumption. Of the 147 participants, 143 participants had available baseline data for analysis. We observed that baseline PCFS score was statistically significantly positively correlated to baseline SHAPS score (β = 0.070, p = 0.045, 95% CI). Our analysis revealed a significant relationship between measures of anhedonia and psychosocial functioning in adults with PCC. Strategies that aim to improve patient-reported outcomes with PCC need to prioritize the prevention and treatment of hedonic disturbances in patients experiencing PCC. [ABSTRACT FROM AUTHOR]

Hitherto no therapeutic has received regulatory approval for the treatment of post-COVID-19 condition (PCC). Cognitive deficits, mood symptoms and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5–20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e. end point). The primary outcome was the change from baseline-to-end point in the Digit Symbol Substitution Test. Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-end point on the Quick Inventory of Depressive Symptomatology 16-item and WHO Wellbeing Scale 5-item, respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function [ P = 0.361, 95% confidence interval (CI) (−0.179, 0.492)]. However, in the fully adjusted model, a significant treatment × time interaction was observed in favour of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (P = 0.012). In addition, a significant improvement in Digit Symbol Substitution Test scores were observed in vortioxetine versus placebo treated participants in those whose baseline CRP was above the mean (P = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms [ P < 0.001, 95% CI (−4.378, −2.323)] and HRQoL [ P < 0.001, 95% CI (2.297, 4.647)] in vortioxetine-treated participants and between the treatment groups [depressive symptoms: P = 0.026, 95% CI (−2.847, −0.185); HRQoL: P = 0.004, 95% CI (0.774, 3.938)]. Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted. [ABSTRACT FROM AUTHOR]

Objective: The World Health Organization (WHO) has defined Post-COVID-19 Condition (PCC) as the onset of symptoms within three months after resolution of an acute SARS-CoV-2 infection, wherein symptoms persist for at least two months and cannot be explained by another medical/psychiatric condition. Persons living with PCC report debilitating symptoms including, but not limited to, depressive symptoms and motivational deficits. The aim of this post-hoc analysis was to evaluate the association between depressive symptoms and motivation in adults with PCC., Methods: We conducted a post-hoc analysis of an 8-week, double-blind, randomized, placebo-controlled trial evaluating adults (18 years or older) in Canada with WHO-defined PCC and cognitive symptoms. This post-hoc analysis is comprised of baseline data that evaluates the association between depressive symptom severity measured by the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16) and motivational systems measured by the Behavioral Inhibition System/Behavioral Activation System Questionnaire (BIS/BAS)., Results: There was a statistically significant association between depressive symptoms and BIS ( β = -0.041 95% CI [-0.066, -0.016], p<0.05), BAS reward responsiveness ( β = 0.043 95% CI [0.012, 0.074], p<0.05), sex ( β = -0.137 95% CI [-0.266, -0.008], p<0.05), and confirmed COVID-19 infection ( β = 0.196 95% CI [0.061, 0.332], p<0.05)., Conclusions: Depressive symptoms were associated with motivational deficits in persons living with PCC. Optimizing treatment for depressive symptoms may potentially improve aspects of motivational impairment amongst persons with PCC. All patients presenting with MDD and a history of COVID-19 infection should be assessed for the presence of PCC.

Background: Post COVID-19 Condition (PCC) is a common and debilitating condition with significant reports of fatigue and psychosocial impairment globally. The extent to which cognitive symptoms and fatigue contribute to reduced quality of life in affected individuals remains clear., Methods: This is a post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial that evaluated the effect of vortioxetine on cognitive function in adults with PCC. The post-hoc analysis herein aimed to determine the overall effect of baseline cognitive function [as measured by the Digit Symbol Substitution Test (DSST)] and baseline fatigue severity [as measured by the Fatigue Severity Scale (FSS)] on baseline health-related quality of life (HRQoL) [as measured by the 5-item World Health Organisation Well-Being Index (WHO-5)]., Results: A total of 200 participants were enrolled in the primary trial. Due to missing baseline data, our statistical analysis included baseline measures of 147 individuals. Our generalized linear model analysis revealed a significant positive correlation between DSST-measured objective cognitive function and self-reported WHO-5-measured HRQoL (β = 0.069, 95% CI [0.006, 0.131], p = 0.032). In contrast, our analysis revealed a significant negative correlation between FSS and WHO-5 scores (β = -0.016, 95% CI [-0.021, -0.011], p < 0.001). The beta-coefficient ratio (β DSST / β FSS = 0.069 / 0.016) is calculated as 4.313., Conclusions: Overall, we observed that increased cognitive function was associated with increased HRQoL at baseline in adults with PCC. Moreover, we observed that increased severity of fatigue symptoms was associated with decreased HRQoL at baseline in adults with PCC. Furthermore, we observed that an improvement in cognitive function would have a four-fold greater impact on HRQoL than the effect generated by improvement in fatigue.

Background: It remains unclear whether subjective and objective measures of cognitive function in Post COVID-19 Condition (PCC) are correlated. The extent of correlation has mechanistic and clinical implications., Methods: This post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial contains baseline data of subjective and objective measures of cognition in a rigorously characterized cohort living with PCC. Herein, we evaluated the association between subjective and objective condition function, as measured by the Perceived Deficits Questionnaire, 20-item (PDQ-20) and the Digit Symbol Substitution Test (DSST) and Trails Making Test (TMT)-A/B, respectively., Results: A total of 152 participants comprised the baseline sample. Due to missing data, our statistical analyses included 150 for self-reported PDQ-20, 147 individuals for combined DSST-measured cognitive function (composite z-score of the Pen/Paper plus Online CogState Version, N combinedDSST ), 71 for in-person DSST-measured cognitive function (Pen/Paper Version), 70 for TMT-A-measured cognitive function, and 70 for TMT-B-measured cognitive function. After adjusting for age, sex, and education, PDQ-20 was significantly correlated with pen-and-paper DSST (β = -0.003, p = 0.002) and TMT-B (β = 0.003, p = 0.008) scores, but not with TMT-A scores (β = -0.001, p = 0.751)., Conclusions: Overall, a statistically significant correlation was observed between subjective and objective cognitive functions. Clinicians providing care for individuals with PCC who have subjective cognitive function complaints may consider taking a measurement-based approach to cognition at the point of care that focuses exclusively on patient-reported measures.