Neurological and Neuropsychological Sequelae of COVID-19 Infection

NCT04745611 | Completed DMC

• 1 other identifier: NL75102.068.20
• Study Type: observational
• Target: 329
• Locations: 1 country
• Sites: 3

Brief Summary

COVID-19 is known to affect the respiratory system but may also have an impact on other organ systems, including the brain. A number of severely ill patients also presents neurological symptoms that may be the result of COVID-19 associated brain damage. The aim of this study is to investigate the presence, type, and severity of brain damage as well as the neurological and neuropsychological sequelae of COVID-19 infection. Further, the impact of this infection on daily life functioning, quality of life, and the emotional well-being of family members will be assessed. In this multicenter study, 6-9 months after hospital discharge patients will undergo a 3-T MRI scan and a neuropsychological examination. Additionally, both patients and their family members will answer several questionnaires at 6- 9 and 12-15 months after hospital discharge. COVID-19 patients previously admitted to a general hospital ward will be compared with patients previously admitted to the intensive-care unit. The proposed study will create a more comprehensive picture of the prolonged COVID-19 effects on the brain, mental, and cognitive well-being. The findings will aid patient care and rehabilitation.

Conditions

COVID-19 Infection

Keywords

Neurological; Neuropsychological; ARDS; Coronavirus; Severe acute respiratory syndrome coronavirus-2; SARS-CoV-2; Infection; Inflammation

Outcome Measures

Primary Outcomes (14)

• Change in participation

  Life participation (social, occupational, mobility) measured by the Utrecht Scale for Evaluation of Rehabilitation-Participation - Restrictions subscale (USER-P-R). The subscale consists of 11 items. Each item score ranges from 0 (not possible at all) to 3 (no difficulty at all), resulting in a total minimum score of 0 and a total maximum score of 33 points, with a higher score indicating less participation restrictions.

  1) 6-9 months and 2) 12-15 months after hospital discharge

• Change in patient quality of life

  Quality of life measured by the EuroQol-5D-5L (EQ-5D-5L). The EQ-5D-5L consists of 5 items with 5 levels. The minimum total score is 5 and the maximum total score is 25, with higher scores indicating more problems.

  1) 6-9 months and 2) 12-15 months after hospital discharge

• Presence of MRI abnormalities

  Presence or absence of MRI abnormalities assessed with a 3T cranial MRI scan

  6-9 months after hospital discharge

• Neurological symptoms

  Measures with the neurological and neuropsychological sequelae of COVID-19 questionnaire (NeNeSCo-Q), a questionnaire that has been created for the purpose of this study to assess the most common neurological symptoms (e.g., reduced sense of taste and/or smell, headaches, neuropathic pain) experienced by patients infected with COVID-19. The questionnaire consists of 9 items being rated with present (yes = 1) and not present (no = 0), resulting in a minimum total score of 0 and a maximum total score of 9.

  6-9 months after hospital discharge

• Deficits in cognition

  Deficits in general cognition are measured with the Montreal Cognitive Assessment (MoCA).

  6-9 months after hospital discharge

• Deficits in memory

  Measured with the Rey's auditory verbal learning test (RAVLT)

  6-9 months after hospital discharge

• Deficits in visual attention & task switching

  Measured with Trail Making Test A/B (TMT)

  6-9 months after hospital discharge

• Deficits in selective attention, cognitive flexibility & processing speed

  Measured with Stroop Test

  6-9 months after hospital discharge

• Deficits in working memory, attention & executive function

  Measured with Digit Span Coding

  6-9 months after hospital discharge

• Change in subjective cognitive complaints

  Assessed with the Checklist for post-IC cognitive complaints (CLC-IC)

  1) 6-9 months and 2) 12-15 months after hospital discharge

• Change in depression/anxiety

  Measured with the Hospital anxiety and depression scale

  1) 6-9 months and 2) 12-15 months after hospital discharge

• Change in post-traumatic stress symptoms

  Measured with the Primary Care Post-Traumatic Stress Disorder (PC-PTSD-5) questionnaire

  1) 6-9 months and 2) 12-15 months after hospital discharge

• Change in family burden

  Measured with the Caregiver Strain Index (CSI)

  1) 6-9 months and 2) 12-15 months after hospital discharge

• Change in family quality of life

  Measured by the EQ-5D-5L. The EQ-5D-5L consists of 5 items with 5 levels. The minimum total score is 5 and the maximum total score is 25, with higher scores indicating more problems.

  1) 6-9 months and 2) 12-15 months after hospital discharge

Secondary Outcomes (1)

• MRI abnormalities (specific)

  6-9 months after hospital discharge

Study Arms (4)

COVID-19 non-ICU patients

Patients who were admitted to one of six recruiting hospitals in the Netherlands due to COVID-19 during the first patient wave (march-june 2020) and who were not admitted to an intensive care unit.

Diagnostic Test: MRI; Diagnostic Test: Neuropsychological assessment; Diagnostic Test: Questionnaires Patient

COVID-19 ICU patients

Patients who were admitted to one of six recruiting hospitals in the Netherlands due to COVID-19 during the first patient wave (march-june 2020) and who were admitted to an intensive care unit.

Diagnostic Test: MRI; Diagnostic Test: Neuropsychological assessment; Diagnostic Test: Questionnaires Patient

COVID-19 non-ICU family members

Close family members of patients who were admitted to one of six recruiting hospitals in the Netherlands due to COVID-19 during the first patient wave (march-june 2020) and who were not admitted to an intensive care unit.

Diagnostic Test: Questionnaires Family

COVID-19 ICU family members

Close family members of patients who were admitted to one of six recruiting hospitals in the Netherlands due to COVID-19 during the first patient wave (march-june 2020) and who were admitted to an intensive care unit.

Diagnostic Test: Questionnaires Family

Interventions

MRI DIAGNOSTIC_TEST

3T cranial MRI with T1-, and T2 weighted imaging, a FLAIR sequence, diffusion-weighted imaging and susceptibility-weighted sequence

COVID-19 ICU patients; COVID-19 non-ICU patients

Neuropsychological assessment DIAGNOSTIC_TEST

Montreal Cognitive Assessment (MoCA), Rey-Auditory Verbal Learning Test (RAVLT), Trail making A/B, Stroop, Digit Span Coding, Judgement of line orientation (JOLO), Boston Naming Task (BNT), Controlled Oral Word Associations Task (COWAT), Category Fuency, Test of Memory Malingering (TOMM)

COVID-19 ICU patients; COVID-19 non-ICU patients

Questionnaires Patient DIAGNOSTIC_TEST

EuroQol-5D-5L (EQ-5D-5L), Utrecht Scale for Evaluation of Rehabilitation-Participation - Restrictions (USER-P-R), NeNeSCo-Q (questionnaire created for this study, including common neurological symptoms), Checklist for post-IC cognitive complaints (CLC-IC self-report), Hospital Anxiety and Depression Scale (HADS), Primary Care Post-Traumatic Stress Disorder (PC-PTSD-5), Utrecht Coping List (UCL) (subscale passive coping), PROMIS physical functioning short form, Items of Insomnia Severity Index (ISI) \& Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Social Support List (SSL-12-I)

COVID-19 ICU patients; COVID-19 non-ICU patients

Questionnaires Family DIAGNOSTIC_TEST

EuroQol-5D-5L (EQ-5D-5L), Utrecht Scale for Evaluation of Rehabilitation-Participation - Restrictions (USER-P-R), Checklist for post-IC cognitive complaints (CLC-IC proxy-report), Hospital Anxiety and Depression Scale (HADS), Primary Care Post-Traumatic Stress Disorder (PC-PTSD-5), Utrecht Coping List (UCL) (subscale passive coping), Social Support List (SSL-12-I), Caregiver Strain Index (CSI)

COVID-19 ICU family members; COVID-19 non-ICU family members

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Former COVID-19 patients who were either admitted to the general hospital ward or the intensive care unit and their respective family members.

You may qualify if:

• Patients:
• Objectified COVID-19 infection for which ICU or non-ICU hospital admission was necessary at one of the participating hospitals
• Age \> 18 years
• Sufficient command of the Dutch language to follow test instructions and understand questionnaires
• Informed consent.
• Family members (if present):
• Within the scope of this study, the term family member will be defined as a person who has good insight into the patient´s daily life functioning (before and after COVID-19 infection). This person can be the spouse, partner, adult child or, in some cases, another individual that plays the most significant role in the patient´s life. The patient will decide who this family member is. We will check the following criteria:
• Family member of a participant with COVID-19 infection as described above;
• Requires participation of the aforementioned family member as COVID-19 patient
• Age \> 18 years
• Sufficient command of the Dutch language to understand questionnaires
• Informed consent.

You may not qualify if:

• Patients:
• objectified cognitive impairments before the hospital admission for the COVID-19 infection
• an unexpected incident leading to severe neurological damage occurring after hospital discharge (such as stroke or traumatic brain injury)
• contra-indications for MRI scanning (e.g. metal implants, cardiac pacemaker, claustrophobia, pregnancy).

Sponsors & Collaborators

• Maastricht University: lead
• Netherlands Brain Foundation: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• UMC Utrecht: collaborator

Study Sites (3)

Maastricht University

Maastricht, Limburg, 6229 ER, Netherlands

Location

Amsterdam Universitair Medische Centra

Amsterdam, Netherlands

Location

Universitair Medische Centra Utrecht

Utrecht, Netherlands

Location

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MeSH Terms

Conditions

COVID-19; Neurologic Manifestations; Coronavirus Infections; Infections; Inflammation

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Officials

• Caroline van Heugten, Prof. Dr.

  Professor of clinical neuropsychology at Maastricht University,

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 9, 2021
• Study Start: December 12, 2020
• Primary Completion: February 21, 2022
• Study Completion: February 21, 2022
• Last Updated: May 2, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)