Cognition, Emotion/Behavior, Functionality and Brain Connectivity in Recovered COVID-19 Patients
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Post-COVID Syndrome
- Sponsor
- Consorci Sanitari de Terrassa
- Enrollment
- 630
- Locations
- 1
- Primary Endpoint
- Differences between groups in verbal memory
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
COVID-19 neurological effects can generate long-term neurobehavioral dysfunction. Our main objective is to examine the impact of COVID-19 on neurobehavior and its relationship with illness severity. Besides, we aim to study structural and functional brain connectivity in a subsample of middle-aged post-COVID-19 individuals. Finally, we aim to develop predictive models of neurobehavioural evolution in post-COVID-19 based on multimodal data.
Detailed Description
NAUTILUS is an observational, cross-sectional, and multicenter study. It will be performed at 22 public hospitals. Two groups of COVID-19 adults (Severe N=210, Moderate-mild N=210, WHO criteria) reporting cognitive complaints will compare to healthy controls (N=210). They will be assessed on neurobehavioral status. We will perform brain MRI in a subsample (N=120, 40 per group), and we will obtain potential biomarkers of neural damage (smell function, retinal blood plexuses integrity, and inflammation). Moreover, we will use machine learning-based algorithms based on demographics, previous pathologies, lifestyle, clinical data, and biomarkers to predict neurobehavioral models. Expected results: Identify the neurobehavioral impact of post-COVID-19 individuals and the discriminative power of multimodal biomarkers in adverse outcomes. Our result would help develop clinically useful models to predict the neurobehavioral impact to develop future personalized and preventive intervention strategies.
Investigators
Maite Garolera
Chief of the Neuropsychology Unit and Director of the Brain, Cognition, and Behavior Research Group (C3-CST) of CST.
Consorci Sanitari de Terrassa
Eligibility Criteria
Inclusion Criteria
- •Confirmed diagnosis of COVID-19 according to WHO interim with signs and symptoms of the severe disease during the acute phase
- •Presence of cognitive complaints after COVID-19 diagnosis
- •Participants have to be discharged from the hospital at least three months before inclusion
- •Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki
Exclusion Criteria
- •Participants have symptoms of delirium according to Delirium Rating Scale-revised 98
- •Established diagnosis before COVID-19 disease of psychiatric, neurological, neurodevelopmental disorder or systemic pathologies are known to cause cognitive deficits
- •Motor or sensory alterations that impede the neuropsychological examination
- •Participants with a metal prosthesis (for MRI studies)
- •Subjects suffering from claustrophobia or requiring sedation due to high anxiety (for MRI studies)
- •PCS from MILD COVID-19 group
- •Confirmed diagnosis of MILD COVID-19 according to WHO interim
- •Presence of cognitive complaints after COVID-19 diagnosis
- •Participants have to be diagnosed with COVID-19 at least three months before inclusion
- •Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki
Outcomes
Primary Outcomes
Differences between groups in verbal memory
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Verbal memory is measured with the Auditory Verbal Learning Test (AVLT). It is a word-learning test where five presentations of a 15-word list are given, each followed by an attempted recall. This is followed by a second 15-word interference list (list B), followed by recall of list A. Delayed recall and recognition are also tested. Higher scores mean a better outcome.
Differences between groups in auditory attention
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Auditory attention is measured with Digit Span Forward. Participants are asked to repeat numbers in the same order as read aloud by the examiner. Higher scores mean a better outcome.
Differences between groups in visual memory
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Visual memory is measured with the Rey-Osterrieth Complex Figure (ROCF) test. The participants are asked to copy complex geometric shapes and then reproduce them from memory. A delayed recall is also tested. Higher scores mean a better outcome.
Differences between groups in depression
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Depression is measured with the Patient Health Questionnaire-9 (PHQ-9) which scores each of the 9 DSM-IV criteria as "not at all" (0 points) to "nearly every day" (3 points). Higher scores mean a worse outcome.
Differences between groups in working memory
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Working memory is measured with Digit Span Backward. Participants are asked to repeat the numbers in the reverse order of that presented by the examiner. Higher scores mean a better outcome.
Differences between groups in language
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Language is measured with the Boston Naming Test. It consists of 60 line drawings of objects of graded difficulty, ranging from very common things to less familiar objects. The total score is the sum of correct answers. Higher scores mean a better outcome.
Differences between groups in psychomotor speed
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Processing speed is measured with Coding subtest of WAIS. Participants are asked to use a key to put in the appropriate symbols for a list of numbers. Higher scores mean a better outcome.
Differences between groups in perceptual reasoning
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Perceptual reasoning is measured with Matrix reasoning subtest of WAIS. Participants are asked to choose which of some possible options the missing picture is from matrix of abstract pictures. Higher scores mean a better outcome.
Differences between groups in executive function
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
A composite score is made with the z-scores of phonemic (sum of the three letters) and semantic fluency, Trail Making Test B (time) and STROOP test (color-word interference total items in 120 seconds).
Differences between groups in social cognition
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Social cognition is measured with the Reading the Mind in the Eyes Test. Participants are asked to choose the emotional state that best describes the eyes, choosing between one of four possible emotions in the 36 photographs of male and female eyes depicting emotional states. Higher scores mean a better outcome.
Differences between groups in anxiety
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Anxiety is measured with the 7-item Generalized Anxiety Disorder Scale (GAD-7), a Likert-type scale with questions ranging from "not at all" (0 points) to "nearly every day" (3 points). The maximum score is 24. Higher scores mean a worse outcome.
Differences between groups in Post-traumatic Stress Disorder
Time Frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Post-Traumatic Stress Disorder is measured with The Post-Traumatic Stress Disorder Checklist (PCL-5), a 20-item questionnaire corresponding to the DSM-5 symptom criteria for PTSD, which scores each criterion as "not at all" (0 points) to "extremely" (4 points). The ratings of items are added together to calculate the total score (range=0-80). Higher scores mean a worse outcome.
Secondary Outcomes
- Differences between groups in Fatigue(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in plasmatic Nerve Growth Factor (NGF)(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in plasmatic Glial Fibrillary Acidic Protein (GFAp)(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in plasmatic C-Reactive Protein (CRP)(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in Quality of Life(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in brain Volumetry(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in plasmatic lipid peroxidation products(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in smell function(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in plasmatic Ferritin(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in White Matter integrity(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in Resting-state connectivity(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups in plasmatic Interleukin- 6 (IL-6)(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)
- Differences between groups retinal plexuses integrity(At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19)