Neurobehavior and Brain Connectivity in Post COVID-19 Patients

Consorci Sanitari de Terrassa630 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

630

Conditions

Post-COVID Syndrome

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

PCS from SEVERE COVID-19 group 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 Exclusion Criteria: * 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) Healthy adult CONTROL group Inclusion Criteria: * Healthy people who have not had COVID-19 * Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki Exclusion Criteria: * the same as COVID-19 groups

Locations (1)

Consorci Sanitari de Terrassa

Terrassa, Barcelona, Spain

Outcomes

Primary Outcomes

Differences between groups in auditory attention

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.

Time frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

Differences between groups in working memory

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.

Time frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

Differences between groups in language

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.

Time frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

Differences between groups in verbal memory

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.

Time frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19

Differences between groups in visual memory

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Differences between groups in Fatigue

Fatigue is measured with the Chalder Fatigue Scale, an 11-item questionnaire measuring the severity of physical and mental fatigue on two separate subscales. Seven items represent physical fatigue (items 1-7) and 4 represent mental fatigue (items 8-11). Each item " less than usual" (0) to " much more than usual" (3). The ratings of items are added together to calculate the total score (range=0-33). High scores represent high levels of fatigue.

Time frame: 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

Quality of life is measured with a 12-item World Health Organization Disability Assessment Schedule-II (WHODAS-II). Patients are asked to state the level of difficulty experienced, considering how they usually do the activity. The scale scores each item as "none" (1) to "cannot do" (5). The total score is calculated with an SPSS syntax, and the range varies from 0 to 100, with higher scores reflecting more significant disability.

Time frame: 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

White matter integrity: tractography measured by MRI

Time frame: 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

Grey and white matter volume measured by MRI

Time frame: 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

Resting state brain activity using fMRI

Time frame: 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)

The plasma levels of IL-6 are measured with enzyme-linked immunosorbent assay (ELISA) Kit

Time frame: 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)

The plasma levels of NGF are measured with ELISA Kit

Time frame: 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)

The plasma levels of GFAp are measured with ELISA Kit

Time frame: 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

The plasma levels of malondialdehyde are measured with TBARS assay method

Time frame: 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

The plasma levels of Ferritin are measured with biochemical assay

Time frame: 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)

The plasma levels of CRP are measured with high sensitivity c-reactive protein ELISA Kit

Time frame: 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

Smell function is evaluated with the University of Pennsylvania Smell Identification Test (UPSIT), which measures the individual's ability to detect odors at a suprathreshold level. The UPSIT comprises four booklets, each of which contains ten pages. An odorized "scratch \& sniff" label is present on each booklet page. The subject scratches the label and then indicates which of the four response alternatives best matches the perceived smell. A score ranging from 6-18 means anosmia, 19-25 means severe microsmia, 26-30 in women and 26-29 in men means moderate microsmia, 31-34 in women and 30-33 in men means mild microsmia and a score of more than 34 in women and 33 in men means normosmia.

Time frame: 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

Retinal plexuses integrity is measured with Optical Coherence Tomography Angiography (OCTA)

Time frame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19