Long-term Neurocognitive and Psychiatric Consequences in Severe COVID-19 Survivors.

Study Overview
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Brief Summary
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Long-term neurocognitive and psychiatric consequences of COVID-19 remain mostly unknown to date. It has been reported that coronaviruses cause direct central nervous system infection (Needham et al. 2020). Besides that, new or worsening cognitive impairment commonly occurs and persists in survivors of intensive care unit (ICU) stay (Hosey & Needham. 2020). The purpose of our study is to search and describe the cognitive and psychiatric long-term consequences of COVID-19 on patients who have been discharged from critical care units. This is an ambidirectional cohort study, that attempts to follow adults discharged from critical Care Units Adults due to COVID-19 up to 12 months after discharge, to evaluate the presence of cognitive impairment, linguistic and phonation function, depression, fatigue, functional gastroenterological symptoms, anxiety, or post traumatic disorder, and performance in activities of daily living and physical response to exercise as well.

Official Title
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Long-term Neurocognitive and Psychiatric Consequences of COVID-19 in Patients Discharged From Critical Care Units. A Cohort Study of the Advance Interdisciplinary Rehabilitation Register (AIRR) Covid-19 Working Group.

Conditions
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Covid19, Neurocognitive Dysfunction

Intervention / Treatment
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* Biological: Exposure: COVID-19 severity


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults over 18 years of age who have been hospitalized at critical care units, who were admitted for a diagnosis of COVID-19 and who present a score on the MOCA® cognitive test of less than 26 points at the time of hospital discharge . Exclusion Criteria: History of underlying cognitive disorder. History of underlying primary psychotic disorder. MOCA® cognitive test score greater than or equal to 26 points at the time of hospital discharge.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 patients discharged from critical care units<br>Adults over 18 years of age who have been hospitalized after COVID-19 diagnosis in the critical care units of Red Salud UC Christus who have been cognitively evaluated with Montreal Cognitive Assessment (MoCA) days prior to their discharge. All patients with a previous history of confirmed neurocognitive or psychotic disorders, prior to hospital admission, were excluded. | Biological: Exposure: COVID-19 severity<br>* COVID-19 severity between 4 to 7 points according the seven-category scale of clinical status reported by Huang et al. (2021) and severe to critical symptomatic levels on spectrum of disease reported by Wu and McGoogan (2020).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive impairment screening | Montreal Cognitive Assessment (MoCA®). Evaluation of cognitive domains (visuospatial, executive function; attention and memory; orientation; language). Min score: 0 Max score: 30 Cut-off for chilean population: < 21 for mild cognitive impairment. < 20 for dementia Setting: Home and online | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive performance | Cambridge Neuropsychological Test Automated Battery (CANTAB®) Included tests: Reaction time test, (RTI) Paired associate learning (PAL) Spatial Working Memory (SWM) Spatial Span (SSP) Rapid Visual Information Processing (RVP) Cambridge Gambling Task (CGT) Intra/Extra Dimensional Set Shift (IED) Stockings of Cambridge (SOC) Scores: z-scores normalized by sex and educational level Setting: Home | 12 months | 
| Neurological Soft Signs | Test: Heidelberg Neurological Soft Signs Scale 16 items on five factors (motor coordination: Ozeretzki's test, diadochokinesis, pronation/supination, finger-to-thumb opposition, speech and articulation; sensory integration: gait, tandem walking, two-point discrimination; complex motor tasks: finger-to-nose test, fist-edge-palm test; right/left and spatial orientation: right/left orientation, graphesthesia, face-hand test, stereognosis; hard signs: arm holding test, mirror movements). All items except for gait, tandem gait, Ozeretzki's test, speech and articulation and right/left orientation are assessed separately for both, right and left sites respectively. Ratings are given on a 0-3 point scale (no/slight/moderate/marked abnormality). Higher scores mean worse outcomes. Min score: 0 Max score: 48 No cut-off point established in the literature. Setting: Home | 12 months | 
| Anxiety | Test: Generalized Anxiety Disorder-7 score The seven items assess (1) feeling nervous, anxious, or on edge; (2) being able to stop or control worrying; (3) worrying too much about different things; (4) trouble relaxing; (5) being restless; (6) becoming easily annoyed or irritable; and (7) feeling afraid as if something awful might happen. Increasing scores on the scale are strongly associated with multiple domains of functional impairment and increasing anxiety. The cut-off point suggested is of ≥10 Min score: 0 Max score: 21 Setting: online | 12 months | 
| Depressive syndrome | Test: Patient Health Questionary-2 (PHQ-2) score for screening of depressive syndrome The cut-off point suggested is of ≥3 Min score: 0 Max score: 6 Setting: online | 12 months | 
| Post Traumatic Stress Disorder | Test: Post Traumatic Checklist for Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) score 20-item self-report measure that assesses the 20 DSM-5 symptoms of Post Traumatic Stress Disorder. The cut-off point suggested is of ≥33 Min score: 0 Max score: 80 Setting: online | 12 months | 
| Physical disability | Test: Barthel Index score Measures physical disability behaviour relating to activities of daily living. Scores of 0-20 indicate total dependency, 21-60 indicate severe dependency, 61-90 indicate moderate dependency, and 91-99 indicates slight dependency. Setting: online | 12 months | 
| Exercise endurance | Performance on 6 minutes- walk test Evaluation of aerobic capacity and exercise endurance. Setting: Home | 12 months | 
| Fatigue | Measured by the Modified fatigue impact scale (MFIS). The MFIS is a modified version of the 40-item Fatigue Impact Scale (FIS), which was originally developed to assess the effects of fatigue on quality of life in patients with chronic diseases. The FIS has patients rate the extent to which fatigue has affected their life in the past 4 weeks on a questionnaire consisting of 10 physical items, 10 cognitive items, and 20 social items, with 0 indicating no problem and 4 indicating extreme problem. The cut-off point suggested is of ≥38 Min score: 0 Max score: 160 Setting: online | 12 months | 
| Global functionality | Post-Covid-19 functional scale 5 levels of severity, where o is non impairment and 5 is the highest level of impairment. Setting: online | 12 months | 
| Quality of life related to health | Test: The 5-level EuroQol 5D health questionnaire. (EQ-5D-5L) Self rated. Min score: 0 Max score: 100 highest score means worst quality of life. Setting: online | 12 months | 
| Muscle strength | Dynamometry Setting: Home | 12 months | 
| Pain severity | Scale: Stanford pain scale Min: 0 represents no pain Max: 10 represents unimaginable or unspeakable pain Setting: online | 12 months | 
| Spontaneous Speech | Spontaneous Speech is a useful research tool to assess the scope of language disorders in people with neurological deficits. Short samples be analyzed during a brief interview and based of 10 linguistics parameters, it will characterized level and the type of language deficit. The 10 linguistic parameters are based on the ALEA method Setting: Home and online | 12 months | 
| Verbal fluency | Verbal fluency (phonological and sematic) will be assed by requesting the participants to elicit word under 1 minute for letter F, A and S and for the category animals. Setting: Home and online | 12 months | 
| complex post-traumatic stress disorder | Test: International Trauma Questionnaire self-report measure for post-traumatic stress disorder (PTSD) and complex post-traumatic stress disorder (CPTSD), corresponding to the diagnostic criteria in the International Classification of Diseases, 11th Revision (ICD-11). Setting: online | 12 months | 
| irritable bowel syndrome | Rome IV criteria Setting: online | 12 months | 
| Insomnia | Scale: Pittsburgh insomnia rating scale Seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. Setting: online | 12 months | 
| Dysautonomia | Scales: Scales for outcomes in Parkinson's dysfunction-autonomic (SCOPA-AUT), Orthostatic hypotension symptom assessment (OHSA) and Orthostatic hypotension activity scale (OHACT). Setting: online | 12 months | 
| Dyspnea | Test: Chronic obstructive pulmonary disease (COPD) assessment test (CAT). Min: 0 Max: 40 CAT ≥10 corresponds to either GOLD Group B or D. Group B patients' preferred treatment is to start either on LABA, or LAMA and if persistent symptoms then combination LAMA/LABA therapy-these are the minimum for patients with CAT Score ≥10. CAT <10 corresponds to GOLD Group A or C. Group A patients' preferred treatment is to start bronchodilator (LABA or LAMA) and evaluate the effect. Setting: online | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Intensive Care Units, Functionality, Fatigue, Anxiety, Insomnia, Long-term cognitive impairment, language disorders, Verbal fluency, Depression, Post traumatic stress, exercise endurance