Greater Role of Cognitive Impairment Over Fatigue in Post-COVID-19 Quality of Life: A Post-Hoc Analysis of a Randomized Controlled Trial (preprint)

BackgroundPost 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. MethodsThis 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)]. ResultsA 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 ({beta} = 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 ({beta} = -0.016, 95% CI [-0.021, -0.011], p < 0.001). The beta-coefficient ratio ({beta}DSST / {beta}FSS = 0.069 / 0.016) is calculated as 4.313. ConclusionsOverall, 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.

Subjective and Objective Measures of Cognitive Function are Correlated in Persons with Post-COVID-19 Condition: A Secondary Analysis of a Randomized Controlled Trial (preprint)

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, NcombinedDSST), 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.

Rumination about the Russo-Ukrainian War and its related factors among individuals in Poland and Ukraine.

The present study aimed to investigate the factors associated with the level of rumination about the war among people living in Poland and Ukraine. This cross-sectional study recruited internet users from advertisements on social media. Levels of rumination, Depression, Anxiety and Stress Scale (DASS), Impact of Event Scale-Revised (IES-R), time spent on news of the war, and related demographic variables were collected. The reliability and construct validity of rumination were estimated. Potential factors associated with the level of rumination were identified using univariate linear regression analysis, and further entered into a stepwise multivariate linear regression model to identify independent factors. Due to the non-normality of distribution, multivariate linear regression with 5000 bootstrap samples was used to verify the results. A total of 1438 participants were included in the analysis, of whom 1053 lived in Poland and 385 lived in Ukraine. The questionnaires on rumination were verified to have satisfactory reliability and validity. After analysis with stepwise and bootstrap regression, older age, female gender, higher DASS and IES-R scores, and longer time spent on news of the war were significantly associated with higher levels of rumination for both people living in Poland and Ukraine. Lower self-rated health status, history of chronic medical illness and coronavirus disease 2019 infection were also positively associated with rumination for people living in Poland. We identified several factors associated with the level of rumination about the Russo-Ukrainian War. Further investigations are warranted to understand how rumination affects individuals' lives during crises such as war.

Association of SARS-CoV-2 Infection with Neurological Symptoms and Neuroimaging Manifestations in the Pediatric Population: A Systematic Review (preprint)

Background Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population.Methods A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged < 18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches.Results A total of 843 nonduplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6,985 individuals were included, where 12.8% of hospitalized patients experienced neurocognitive impairments: MIS-C (24.2%), neuroinflammation (10.1%), and encephalopathy (8.1%) were the most common disorders; headaches (16.8%) and seizures (3.8%) were the most common symptoms. Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%).Conclusion Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.

A Multinational Study on the Protective and Risk Factors Associated with Mental Health Parameters in the General Population During the COVID-19 Pandemic: A Study in the Asia-Europe-North America Cohort (preprint)

Background: The novel Coronavirus-2019 (COVID-19) was declared a pandemic by the World Health Association (WHO) in March 2020, impacting the lifestyles, economy, physical and mental health of individuals globally. Little is known about the relationship between the impact of COVID-19 and one’s mental health status, and thus research needs to be conducted to identify the factors involved and develop tailored evidence-based strategies in response to reduce the adverse psychological impact. Methods: From February to June 2020, we conducted an online Global Mental Health survey which recruited participants via a respondent-driven sampling country in 8 countries (China, Pakistan, Philippines, Iran, Poland, Spain, USA and Vietnam). The online survey collected information on demographic characteristics, physical symptoms and health service utilisation, contact history, knowledge and concerns regarding COVID-19, precautionary measures taken and additional health information variables among the countries involved. The psychological impact was measured by the Impact of Event Scale-Revised (IES-R) questionnaire and the mental health status was measured by the Depression, Anxiety and Stress Scale (DASS-21). Results: There were 5555 participants involved in the study, 31.4% male and 68.6% female, with an age range of 12-to above 50 years of age. There were significant differences in the mean IES-R and DASS-21 scores between the 8 countries (F(7, 55477) = 71.605, η2=0.085, p<0.001). China had the highest IES-R score (mean=32.98, SD=15.42). Poland and Pakistan were found to be the two countries with the highest levels of anxiety, depression and stress; conversely, Vietnam had the lowest scores in stress (mean = 3.80, SD = 5.81), anxiety (mean = 2.10, SD = 4.91) and depression (mean = 2.28, SD = 5.43). Female gender, age older than 50 years, crowded home environment, unemployment and student status were significant associated with adverse mental health (p<0.05). However, higher education background, greater level of satisfaction with health information, staying with family members, spending less than 2 hours a day monitoring health information, taking suitable precautionary measures, use of face masks and less time spent at home were found to be protective factors for mental health (p<0.05). Interpretation: During the height of the COVID-19 pandemic, the mental health of the global population was significantly affected as shown empirically by the results of our study, and each country faced their own set of unique challenges in their response to COVID-19. Our findings have identified protective and risk factors associated with mental health that can help us to develop targeted psychological interventions for those who are more vulnerable during this pandemic.Funding Statement: This study has the following funding sources: Huaibei Normal University, China, Ministry of Science and Higher Education in Poland under the 2019-2022 program, Regional Initiative of Excellence", project number 012 / RID / 2018/19, National University of Singapore iHeathtech Other Operating Expenses (R-722-000-004-731) and Vingroup Innovation Foundation (VINIF) COVID research grant (VINIF.2020.Covid19.DA07) in Vietnam.Declaration of Interests: None declared.Ethics Approval Statement: The study was approved by the Institutional Review Boards from each country, China (Huaibei Normal University of China, HBU-IRB2020-001/002), Philippines (University of Philippines Manila Research Ethics Board, UPMREB 2020-198-01), Poland (SWPS University, WKEB62/04/2020), Spain (Complutense University of Madrid of Spain, Pr_2019_20_027), Vietnam (Hanoi Medical University, QD 75/QD-YHDP&YHDP) and the US (East Carolina University, UMCIRB 20-000838). Approval was also obtained from the relevant Iranian and Pakistani committees. All respondents provided informed consent. The collected data were anonymous and treated as confidential.