Clinical trial NCT05307549: COVID-19 and Brain: Cognition and Mental Health
Official title: COVID-19 and Brain: Cognition and Mental Health
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Keywords: COVID-19
Cognition
Mental Health
Neuroimaging
MachineLearning
Lead sponsor: University of Barcelona
Sponsor class: OTHER
Collaborators: name: Consorci Sanitari de Terrassa
name: Universitat Politècnica de Catalunya
First posted: 2022-04-01
Enrollment: 200
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: COVID-19 survivors 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: The main goal of DIANA is to investigate the potential discriminative power of multimodal biomarkers in COVID adverse outcomes. The study of the neuropathological underlying mechanisms in COVID from a translational approach at: (1) the behavioural-clinical level from cognitive, emotional and functional data; (2) the brain connectome level from structural and functional imaging data; and (3) biogenetic level from blood and stool data. Moreover, the investigators will develop machine learning based predictive models of cognitive, mental health, functionality, and brain connectivity evolution in post-COVID syndrome patients.

Detailed description: DIANA project is an observational, descriptive, and cross-sectional study in which participants will not be randomized. Case people (adult survivors of severe COVID-19 N=134) will compare to healthy adult controls (n=66). It is a multicentric study where all the participants will be recruited from eleven Catalan public health institutions. The participants will be assessed on cognitive, emotional and functional status. The investigators will obtain a blood sample to study inflammation, vascular risk, growth factors, angiogenesis, neurogenesis, and cellular metabolism biomarkers and genes, and a stool sample for gut microbiota study. Structural and functional MRI will be performed on a subgroup of participants 40 COVID-19 survivors and 40 healthy controls.

The objectives of the project are:

1. To examine the impact of the COVID-19 illness on cognition, emotion/behavior, and functionality.
2. To examine the possible affectation in brain grey and white matter and functional connectivity of severe forms COVID-19 survivors.
3. To relate demographic characteristics, previous pathologies, lifestyle, baseline cerebral status, genetic polymorphism, and clinical data in acute illness with cognitive, mental health, functionality, and brain connectivity outcomes of severe forms COVID-19 survivors.
4. To study the post-COVID-19 biomarkers of inflammation, vascular risk, growth factors, angiogenesis, neurogenesis, and cellular metabolism and its relationship with the cognitive, mental health, functionality, and brain connectivity outcomes of severe forms COVID-19 survivors.
5. To quantify the presence of different bacterial species in the post COVID stool sample and analyze the wealth and diversity of the diverse populations. To study if these values are related to the performance of neuropsychological and behavioral tests and neuroimaging data.
6. - To develop machine learning based predictive models of cognitive, mental health, functionality and brain connectivity evolution in post COVID 19 survivors.

Eligibility criteria: Post-COVID 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)

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 survivors

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 D-Dimer
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 NT-proB-type Natriuretic Peptide (BNP)
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 Thrombomodulin
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 Endothelin 1
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 Microbiota data
timeFrame: At the time of inclusion of the participant, between 3 and 12 months from the start of COVID-19
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: University of Barcelona
Study officials:
affiliation: University of Barcelona
name: Carme Junqué, PhD
role: STUDY_DIRECTOR
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.