Clinical trial NCT05307575: Neurobehavior and Brain Connectivity in Post COVID-19 Patients
Official title: Cognition, Emotion/Behavior, Functionality and Brain Connectivity in Recovered COVID-19 Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Post-COVID Syndrome
Keywords: COVID-10
Cognition
Mental Health
Neuroimage
Machine Learning
Lead sponsor: Consorci Sanitari de Terrassa
Sponsor class: OTHER
Collaborators: name: University of Barcelona
name: Universitat Politècnica de Catalunya
First posted: 2022-04-01
Enrollment: 630
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: PCS from severe and mild COVID-19 group will be recruited in hospital and primary care services.

The control population will be searched in the general population through primary care centers, the media, social networks, and they will be offered to participate in the study without remuneration.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Differences between groups in auditory attention
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in working memory
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in language
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in verbal memory
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in visual memory
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in psychomotor speed
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in perceptual reasoning
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in executive function
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in social cognition
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in anxiety
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in depression
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in Post-traumatic Stress Disorder
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Secondary outcomes:
measure: Differences between groups in Fatigue
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in Quality of Life
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in White Matter integrity
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in brain Volumetry
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in Resting-state connectivity
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in plasmatic Interleukin- 6 (IL-6)
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in plasmatic Nerve Growth Factor (NGF)
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in plasmatic Glial Fibrillary Acidic Protein (GFAp)
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in plasmatic lipid peroxidation products
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in plasmatic Ferritin
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in plasmatic C-Reactive Protein (CRP)
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups in smell function
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
measure: Differences between groups retinal plexuses integrity
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Other outcomes:
Locations:
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
Study officials:
affiliation: Consorci Sanitari de Terrassa
name: Maite Garolera, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ariza M, Cano N, Segura B, Adan A, Bargallo N, Caldu X, Campabadal A, Jurado MA, Mataro M, Pueyo R, Sala-Llonch R, Barrue C, Bejar J, Cortes CU; NAUTILUS-Project Collaborative Group; Junque C, Garolera M. Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints. Front Aging Neurosci. 2022 Oct 20;14:1029842. doi: 10.3389/fnagi.2022.1029842. eCollection 2022.