Sleep quality in individuals with post-COVID-19 condition: relation with emotional, cognitive and functional variables

Anxiety; COVID-19; Sleep qualityAnsietat; COVID 19; Qualitat del sonAnsiedad; COVID-19; Calidad de sueñoThe study aimed to assess sleep quality in PCC patients and its predictors by analysing its relationship with emotional, cognitive and functional variables, as well as possible differences based on COVID-19 severity. We included 368 individuals with PCC and 123 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575). We assessed sleep quality (Pittsburgh Sleep Quality Index, PSQI), anxiety (Generalized Anxiety Disorder, GAD-7), depression (Patient Health Questionnaire, PHQ-9), global cognition (Montreal Cognitive Assessment, MoCA), everyday memory failures (Memory Failures of Everyday Questionnaire, MFE-30), fatigue (Chadler Fatigue Questionnaire, CFQ), quality of life (European Quality of Life-5 Dimensions, EQ-5D), and physical activity levels (International Physical Activity Questionnaire, IPAQ). 203 were nonhospitalized, 83 were hospitalized and 82 were admitted to the intensive care unit (ICU). We found statistically significant differences in the PSQI total score between the PCC and HC groups (p < 0.0001), but there were no differences among the PCC groups. In the multiple linear regressions, the PHQ-9 score was a predictor of poor sleep quality for mild PCC patients (p = 0.003); GAD-7 (p = 0.032) and EQ-5D (p = 0.011) scores were predictors of poor sleep quality in the hospitalized PCC group; and GAD-7 (p = 0.045) and IPAQ (p = 0.005) scores were predictors of poor sleep quality in the group of ICU-PCC. These results indicate that worse sleep quality is related to higher levels of depression and anxiety, worse quality of life and less physical activity. Therapeutic strategies should focus on these factors to have a positive impact on the quality of sleep.L'estudi pretenia avaluar la qualitat del son en pacients amb PCC i els seus predictors mitjançant l'anàlisi de la seva relació amb variables emocionals, cognitives i funcionals, així com les possibles diferències en funció de la gravetat de la COVID-19. Es van incloure 368 individus amb PCC i 123 controls saludables (HC) del projecte NAUTILUS (NCT05307549 i NCT05307575). Es va avaluar la qualitat del son (índex de qualitat del son de Pittsburgh, PSQI), l'ansietat (trastorn d'ansietat generalitzada, GAD-7), la depressió (Patient Health Questionnaire, PHQ-9), la cognició global (Montreal Cognitive Assessment, MoCA), errors de memòria diària (memòria). Falles del Qüestionari diari, MFE-30), fatiga (Qüestionari de Fatiga de Chadler, CFQ), qualitat de vida (Qualitat de Vida Europea-5 Dimensions, EQ-5D) i nivells d'activitat física (Questionari Internacional d'Activitat Física, IPAQ). 203 estaven no hospitalitzats, 83 estaven hospitalitzats i 82 estaven ingressats a la unitat de cures intensives (UCI). Hem trobat diferències estadísticament significatives en la puntuació total de PSQI entre els grups PCC i HC (p <0, 0001), però no hi va haver diferències entre els grups PCC. En les regressions lineals múltiples, la puntuació PHQ-9 va ser un predictor de la mala qualitat del son per als pacients amb PCC lleus (p = 0,003); Les puntuacions GAD-7 (p = 0,032) i EQ-5D (p = 0,011) van ser predictors de mala qualitat del son en el grup de PCC hospitalitzat; i les puntuacions de GAD-7 (p = 0,045) i IPAQ (p = 0,005) van ser predictors de mala qualitat del son en el grup d'UCI-PCC. Aquests resultats indiquen que una pitjor qualitat del son està relacionada amb nivells més alts de depressió i ansietat, pitjor qualitat de vida i menys activitat física. Les estratègies terapèutiques haurien de centrar-se en aquests factors per tenir un impacte positiu en la qualitat del son.This research was supported by: Grants from the Agency for Management of University and Research Grants (AGAUR) from the Generalitat de Catalunya (Pandemies, 202PANDE00053) and La Marató de TV3 Foundation (202111-30-31-32) to MG.- Grants from the Instituto de Salud Carlos III de Madrid (PI22/01687, ISCIII) and Agency for Management of University and Research Grants (2021SGR 00761) to GPR

Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints

COVID-19; Cognitive function; Neuropsychological testCOVID-19; Función cognitiva; Test neuropsicológicoCOVID-19; Funció cognitiva; Test neuropsicològicOne of the most prevalent symptoms of post-COVID condition is cognitive impairment, which results in a significant degree of disability and low quality of life. In studies with large sample sizes, attention, memory, and executive function were reported as long-term cognitive symptoms. This study aims to describe cognitive dysfunction in large post-COVID condition individuals, compare objective neuropsychological performance in those post-COVID condition individuals with and without cognitive complaints, and identify short cognitive exams that can differentiate individuals with post-COVID symptoms from controls. To address these aims, the Nautilus project was started in June 2021. During the first year, we collected 428 participants' data, including 319 post-COVID and 109 healthy controls (18-65 years old) from those who underwent a comprehensive neuropsychological battery for cognitive assessment. Scores on tests assessing global cognition, learning and long-term memory, processing speed, language and executive functions were significantly worse in the post-COVID condition group than in healthy controls. Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were significant in the binomial logistic regression model and could effectively distinguish patients from controls with good overall sensitivity and accuracy. Neuropsychological test results did not differ between those with and without cognitive complaints. Our research suggests that patients with post-COVID conditions experience significant cognitive impairment and that routine tests like the Montreal Cognitive Assessment, digit symbol, and phonetic verbal fluency test might identify cognitive impairment. Thus, the administration of these tests would be helpful for all patients with post-COVID-19 symptoms, regardless of whether cognitive complaints are present or absent

Cognitive reserve, depressive symptoms, obesity, and change in employment status predict mental processing speed and executive function after COVID-19

Post-COVID-19 condition; Mental speed processing; Logistic regressionCondición post-COVID-19; Procesamiento de velocidad mental; Regresión logísticaEstat post-COVID-19; Processament de velocitat mental; Regressió logísticaThe risk factors for post-COVID-19 cognitive impairment have been poorly described. This study aimed to identify the sociodemographic, clinical, and lifestyle characteristics that characterize a group of post-COVID-19 condition (PCC) participants with neuropsychological impairment. The study sample included 426 participants with PCC who underwent a neurobehavioral evaluation. We selected seven mental speed processing and executive function variables to obtain a data-driven partition. Clustering algorithms were applied, including K-means, bisecting K-means, and Gaussian mixture models. Different machine learning algorithms were then used to obtain a classifier able to separate the two clusters according to the demographic, clinical, emotional, and lifestyle variables, including logistic regression with least absolute shrinkage and selection operator (LASSO) (L1) and Ridge (L2) regularization, support vector machines (linear/quadratic/radial basis function kernels), and decision tree ensembles (random forest/gradient boosting trees). All clustering quality measures were in agreement in detecting only two clusters in the data based solely on cognitive performance. A model with four variables (cognitive reserve, depressive symptoms, obesity, and change in work situation) obtained with logistic regression with LASSO regularization was able to classify between good and poor cognitive performers with an accuracy and a weighted averaged precision of 72%, a recall of 73%, and an area under the curve of 0.72. PCC individuals with a lower cognitive reserve, more depressive symptoms, obesity, and a change in employment status were at greater risk for poor performance on tasks requiring mental processing speed and executive function.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was supported by the European Archives of Psychiatry and Clinical Neuroscience Agency for Management of University and Research Grants (AGAUR) from the Generalitat de Catalunya (Pandemies, 2020PANDE00053), the La Marató de TV3 Foundation (202111–30-31–32), the Ministerio de Ciencia e Innovación (TED2021-130409B-C55)

Cognitive and emotional predictors of quality of life and functioning after COVID-19

Quality of life; Cognitive and emotional predictors; COVID-19Calidad de vida; Predictores cognitivos y emocionales; COVID-19Qualitat de vida; Predictors cognitius i emocionals; COVID-19Objective: A long-term decline in health-related quality of life (HRQoL) has been reported after coronavirus disease 2019 (COVID-19). Studies with people with persistent symptoms showed inconsistent outcomes. Cognition and emotion are important determinants in HRQoL, but few studies have examined their prognostic significance for HRQoL and functionality in post-COVID patients with persisting symptoms. We aimed to describe QoL, HRQoL, and functioning in individuals post-COVID with varying COVID-19 severities and to investigate the predictive value of cognitive and emotional variables for QoL, HRQoL, and functioning. Methods: In total, 492 participants (398 post-COVID and 124 healthy controls) underwent a neurobehavioral examination that included assessments of cognition, mood, QoL/HRQoL (WHOQOL-BREF, EQ-5D), and functioning (WHODAS-II). Analysis of covariance and linear regression models were used to study intergroup differences and the relationship between cognitive and emotional variables and QoL and functioning. Results: The Physical and Psychological dimensions of WHOQoL, EQ-5D, and WHODAS Cognition, Mobility, Life Activities, and Participation dimensions were significantly lower in post-COVID groups compared with a control group. Regression models explaining 23.9%-53.9% of variance were obtained for the WHOQoL-BREF dimensions and EQ-5D, with depressive symptoms, post-COVID symptoms, employment status, income, and mental speed processing as main predictors. For the WHODAS, models explaining 17%-60.2% of the variance were obtained. Fatigue, depressive symptoms, mental speed processing, and post-COVID symptoms were the main predictors. Interpretation: QoL/HRQoL and functioning after COVID-19 in individuals with persistent symptoms were lower than in non-affected persons. Depressive symptoms, fatigue, and slower mental processing speed were predictors of lower QoL/HRQoL and functioning.This research was supported by the Agency for Management of University and Research Grants (AGAUR) from the Generalitat de Catalunya (Pandemies, 202PANDE 00053) and La Marato de TV3 Foundation (202111-30- 31-32)

Semantic Fuzzing with Zest

Programs expecting structured inputs often consist of both a syntactic analysis stage, which parses raw input, and a semantic analysis stage, which conducts checks on the parsed input and executes the core logic of the program. Generator-based testing tools in the lineage of QuickCheck are a promising way to generate random syntactically valid test inputs for these programs. We present Zest, a technique which automatically guides QuickCheck-like randominput generators to better explore the semantic analysis stage of test programs. Zest converts random-input generators into deterministic parametric generators. We present the key insight that mutations in the untyped parameter domain map to structural mutations in the input domain. Zest leverages program feedback in the form of code coverage and input validity to perform feedback-directed parameter search. We evaluate Zest against AFL and QuickCheck on five Java programs: Maven, Ant, BCEL, Closure, and Rhino. Zest covers 1.03x-2.81x as many branches within the benchmarks semantic analysis stages as baseline techniques. Further, we find 10 new bugs in the semantic analysis stages of these benchmarks. Zest is the most effective technique in finding these bugs reliably and quickly, requiring at most 10 minutes on average to find each bug.Comment: To appear in Proceedings of 28th ACM SIGSOFT International Symposium on Software Testing and Analysis (ISSTA'19

Can Personality Traits Affect Sleep Quality in Post-COVID-19 Patients?

Objectives: In the present study, we aimed (i) to describe the personality traits of a cohort of post-COVID-19 condition (PCC) patients compared with a healthy control (HC) group, (ii) to evaluate the relationship between sleep quality and personality traits, and (iii) to investigate whether this relationship differs according to disease severity. Methods: We included 599 participants from the Nautilus Project (ClincalTrials.gov IDs: NCT05307549 and NCT05307575) with an age range from 20 to 65 years old. Of 599 participants, 280 were nonhospitalized (mild PCC), 87 were hospitalized (hospitalized PCC), 98 were in the PCC-ICU, and 134 were in the HC group. We assessed sleep quality with the Pittsburgh Sleep Quality Index (PSQI) and personality traits with the NEO Five-Factor Inventory (NEO FFI). Results: We found that mild-PCC patients had higher scores of neuroticism than HCs (p < 0.001) and ICU-PCC patients did (p = 0.020). The higher the neuroticism score was, the higher the total PSQI score (B 0.162; p < 0.001), the worse the sleep latency (B 0.049; p < 0.001), the greater the degree of sleep disturbance (B 0.060; p < 0.001), the greater the use of sleeping medication (B 0.035; p = 0.033), and the greater the incidence of daytime disturbances (B 0.065; p < 0.001) among the PCC patients. High neuroticism is also an indicator of worse sleep quality in mild-PCC (t = 3.269; p 0.001) and hospitalized-PCC (t = 6.401; p < 0.001) patients and HCs (t = 4.876; p < 0.001) but not in ICU-PCC patients. Conclusions: Although neuroticism affected sleep quality in both the PCC patients and HCs, the clinical implications and magnitude of the relationship were more significant in the PCC group. Specific and multidimensional interventions are needed to treat sleep problems in this population, and the influence of their personality traits should be considered

Mining deep-ocean mineral deposits: what are the ecological risks?

A key question for the future management of the oceans is whether the mineral deposits that exist on the seafloor of the deep ocean can be extracted without significant adverse effects to the environment. The potential impacts of mining are wide-ranging and will vary depending on the type of metal-rich mineral deposit being mined. There is, currently, a significant lack of information about deep-ocean ecosystems and about potential mining technologies: thus, there could be many unforeseen impacts. Here, we discuss the potential ecological impacts of deep-ocean mining and identify the key knowledge gaps to be addressed. Baseline studies must be undertaken, as well as regular monitoring of a mine area, before, during, and after mineral extraction.The attached document is the author’s submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

COVID-19 severity is related to poor executive function in people with post-COVID conditions

Patients with post-coronavirus disease 2019 (COVID-19) conditions typically experience cognitive problems. Some studies have linked COVID-19 severity with long-term cognitive damage, while others did not observe such associations. This discrepancy can be attributed to methodological and sample variations. We aimed to clarify the relationship between COVID-19 severity and long-term cognitive outcomes and determine whether the initial symptomatology can predict long-term cognitive problems. Cognitive evaluations were performed on 109 healthy controls and 319 post-COVID individuals categorized into three groups according to the WHO clinical progression scale: severe-critical (n = 77), moderate-hospitalized (n = 73), and outpatients (n = 169). Principal component analysis was used to identify factors associated with symptoms in the acute-phase and cognitive domains. Analyses of variance and regression linear models were used to study intergroup differences and the relationship between initial symptomatology and long-term cognitive problems. The severe-critical group performed significantly worse than the control group in general cognition (Montreal Cognitive Assessment), executive function (Digit symbol, Trail Making Test B, phonetic fluency), and social cognition (Reading the Mind in the Eyes test). Five components of symptoms emerged from the principal component analysis: the "Neurologic/Pain/Dermatologic" "Digestive/Headache", "Respiratory/Fever/Fatigue/Psychiatric" and "Smell/ Taste" components were predictors of Montreal Cognitive Assessment scores; the "Neurologic/Pain/Dermatologic" component predicted attention and working memory; the "Neurologic/Pain/Dermatologic" and "Respiratory/Fever/Fatigue/Psychiatric" components predicted verbal memory, and the "Respiratory/Fever/Fatigue/Psychiatric," "Neurologic/Pain/Dermatologic," and "Digestive/Headache" components predicted executive function. Patients with severe COVID-19 exhibited persistent deficits in executive function. Several initial symptoms were predictors of long-term sequelae, indicating the role of systemic inflammation and neuroinflammation in the acute-phase symptoms of COVID-19.

Structural brain changes in post-COVID condition and its relationship with cognitive impairment

Post-COVID condition; Brain structure; Cognitive performanceCondició post-COVID; Estructura cerebral; Deteriorament cognitiuCondición post-COVID; Estructura cerebral; Deterioro cognitivoIt has been estimated that ∼4% of individuals infected with SARS-CoV-2 will be diagnosed with post-COVID condition. Previous studies have evidenced the presence of cognitive dysfunction and structural brain changes in infected individuals; however, the relationship between structural changes and cognitive alterations in post-COVID condition is still not clear. Consequently, the aim of this work is to study structural brain alterations in post-COVID condition patients after almost 2 years of infection and their likely relationship with patients' cognitive impairment. Additionally, the association with blood biomarkers and clinical variables was also explored. One hundred and twenty-eight individuals with post-COVID condition and 37 non-infected healthy controls from the Nautilus Project (ClinicalTrials.gov IDs: NCT05307549 and NCT05307575) underwent structural brain magnetic resonance imaging and a comprehensive neuropsychological assessment. A subsample of 66 post-COVID participants also underwent blood extraction to obtain levels of blood biomarkers. Cortical thickness and subcortical volumes were obtained and analysed using FreeSurfer (v7.1). FMRIB Software Library software (v6.0.4) was used to perform grey matter voxel-based analysis and to study microstructural white matter integrity. Patients with post-COVID performed significantly worse in working and verbal memory, processing speed, verbal fluency and executive functions, compared to healthy controls. Moreover, patients with post-COVID showed increased cortical thickness in the right superior frontal and the right rostral middle frontal gyri that negatively correlated with working memory performance. Diffusion tensor imaging data showed lower fractional anisotropy in patients in the right superior longitudinal fasciculus, the splenium and genu of the corpus callosum, the right uncinate fasciculus and the forceps major, that negatively correlated with subjective memory failures. No differences in blood biomarkers were found. Once patients were classified according to their cognitive status, post-COVID clinically cognitively altered presented increased cortical thickness compared to those classified as non-cognitively altered. In conclusion, our study showed that grey and white matter brain changes are relevant in this condition after almost 2 years of infection and partly explain long-term cognitive sequelae. These findings underscore the critical importance of monitoring this at-risk population over time.This work was sponsored by the Generalitat de Catalunya (SGR 2021SGR00801), Agency for Management of University and Research Grants (AGAUR) from the Generalitat de Catalunya (Pandemies, 202PANDE00053), Fundació la Marató de TV3 (202111-30-31-32), TED2021-130409BC51/MCIU/AEI/10.13039/501100011033 and TED2021- 130409A-C52/MCIU/AEI/10.13039/501100011033 by Ministerio de Ciencia, Innovación y Universidades (MCIU)/ Agencia Estatal de investigación (AEI) and NextGenerationEU/ Plan de Recuperación, Transformación y Resiliencia (PRTR) and supported by María de Maeztu Unit of Excellence (Institut de Neurociències, Universitat de Barcelona) (CEX2021-001159-M), Ministerio de Ciencia e Innovación. J.P. was supported by a fellowship from Ministerio de Economía y Competitividad (PRE2021-099674). J.O. was supported by a fellowship from Ministerio de Ciencia, Innovación y Universidades (PRE2018-086675). I.R. was supported by a fellowship from ‘la Caixa’ Foundation (LCF/BQ/ DR22/11950012)

Functional brain abnormalities in post COVID-19 condition and their relationship with cognition.

After COVID-19 infection, some patients develop a post-COVID condition (PCC) that is popularly referred to as long COVID. Among its symptoms is persistent cognitive dysfunction that is potentially linked to altered brain functional connectivity (FC). While research has explored functional reorganization in patients with PCC, the intra- and inter- network connectivity and its relationship with cognitive status and clinical outcomes remain unclear. In this study, we recruited 121 individuals with PCC (67 with, and 54 without, cognitive impairment), 20 months after infection, along with 37 non-infected healthy controls from the NAUTILUS Project (ClinicalTrials.gov IDs: NCT05307549 and NCT05307575). Participants underwent resting-state functional magnetic resonance imaging and comprehensive neuropsychological assessment. Resting-state networks were characterized using independent component analyses, dual regression and network modelling for individual FC characterization. Group differences in intra- and inter-network FC, and their associations with clinical and neuropsychological data, were studied. Significance was set at a corrected p-value of < 0.05. Patients with PCC showed increased intra-network FC in 10 cognitively relevant networks, including the default mode, salience, executive control, auditory and basal ganglia networks, correlating positively with general cognition (Montreal Cognitive Assessment scores), time since infection, fatigue and subjective memory failures. Increased inter-network FC between default mode and sensorimotor networks was also observed. Increases in FC may reflect an inefficient compensatory mechanism in patients with PCC, associated with fatigue, subjective memory complaints and persistence of PCC.