Neurocognitive Impairment in Patients With COVID-19 (NCoV)

• ClinicalTrials.gov Identifier: NCT04359914
• Recruitment Status: Active, not recruiting
• First Posted: April 24, 2020
• Last Update Posted: May 18, 2022
• Sponsor: University of Rostock
• Collaborators: Ludwig-Maximilians - University of Munich; University College, London
• Information provided by (Responsible Party): Dr. Johannes Ehler, MD, University of Rostock

Study Description

Brief Summary:

Delirium and acute neurocognitive impairment are increasingly observed in adult and pediatric patients with COVID-19. Prospective clinical studies combining clinical and laboratory examinations including specific biomarkers of neuroaxonal injury were not performed for COVID-19. The value of biomarkers of neuroaxonal injury was proven in preliminary studies. These biomarkers could thus contribute to the systematic detection of neurocognitive impairment in patients with COVID-19. Due to worldwide increasing numbers of hospitalized patients with COVID-19, biomarkers of neuroaxonal injury are highly valuable to detect and monitor cognitive impairment, especially with regard to limited resources available to perform time-consuming brain imaging.

Biomarkers of neuroaxonal injury are therefore not only of great interest to detect neurocognitive impairment but also to quantify the severity of brain injury in patients with COVID-19.

Condition or disease
Critical Illness; COVID-19; Central Nervous System Injury; Delirium; Encephalopathy

Detailed Description:

This is a multicenter observational study evaluating the incidence and severity of neurocognitive impairment in adult and pediatric patients with COVID-19. All study participants will be assessed by clinical and neurological examination as well as comprehensive laboratory tests using biomarkers of neuroaxonal injury at study day 1 (day of study inclusion), day 3, day 7 and day of hospital discharge. A panel of biomarkers (among others NSE, S100B and neurofilament proteins) will be measured. Clinical assessment will be performed using validated delirium tests (among others CAM-ICU, ICDSC) and scales to assess the neurocognitive performance of study participants before and three months after study inclusion (among others Short Blessed Test).

A group of patients with a comparable severity of disease but without the detection of SARS-Cov-2 will serve as control group and will undergo the same clinical and laboratory examinations.

We hypothesize, that:

• patients with COVID-19 are more likely to develop delirium and neurocognitive impairment than patients without COVID-19
• patients with a preexisting neurocognitive deficit are more vulnerable to neurocognitive impairment in the course of COVID-19 than patients without a preexisting neurocognitive deficit
• Specific biomarkers of neuroaxonal injury correlate with the clinical severity of acute neurocognitive impairment and can predict the 3-month neurocognitive outcome of patients with COVID-19

Study Design

• Study Type: Observational
• Estimated Enrollment: 80 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Biomarker-guided Assessment of Neurocognitive Impairment in Patients With COVID-19 - a Multicenter Case-control Study
• Actual Study Start Date: April 15, 2020
• Actual Primary Completion Date: March 31, 2021
• Estimated Study Completion Date: July 31, 2022

Groups and Cohorts

Group/Cohort
NCoV-A-COVID; adult patients of every age; admission to hospital with suspected COVID-19 disease; confirmed SARS-CoV-2 infection within 48 hours after admission
NCoV-A-CONTROL; adult patients of every age; admission to hospital with suspected COVID-19 disease; exclusion of SARS-CoV-2 infection within 48 hours after admission
NCoV-P-COVID; pediatric patients; admission to hospital with suspected COVID-19 disease; confirmed SARS-CoV-2 infection within 48 hours after admission
NCoV-P-CONTROL; pediatric patient; admission to hospital with suspected COVID-19 disease; exclusion of SARS-CoV-2 infection within 48 hours after admission

Outcome Measures

Primary Outcome Measures :

1. Incidence of delirium/neurocognitive impairment in adult and pediatric patients with COVID-19 compared to patients without COVID-19 [ Time Frame: Day 90 ]
   Assessment of neurocognitive impairment using validated tools
2. Change in neuroaxonal injury biomarker levels in patients with COVID-19 compared to patients without COVID-19 [ Time Frame: Change from baseline biomarker levels at day 28 ]
   Measurement of biomarker levels (e.g. NSE, S100B, neurofilament proteins) derived from blood samples
3. Neurocognitive 3-months outcome in patients with COVID-19 compared to patients without COVID-19 [ Time Frame: Day 90 ]
   Assessment of the neurocognitive performance of patients using validated tests (e.g. Short Blessed Test)
4. Neurocognitive 3-months outcome in patients with COVID-19 compared to patients without COVID-19 [ Time Frame: Change from baseline IQCODE results at day 90 ]
   Assessment of the change in the neurocognitive performance of patients using validated tests (e.g. IQCODE)

Secondary Outcome Measures :

1. Quality of life in patients with COVID-19 compared to patients without COVID-19 after hospital discharge [ Time Frame: Day 90 ]
   Assessment of the overall quality of life using validated tests [e.g. Modified Rankin Scale with a range from 0 (no symptoms) to 6 (dead)]
2. Length of hospital stay in patients with COVID-19 compared to patients without COVID-19 [ Time Frame: 1 year ]
   Cumulative days in hospital
3. 90-day survival in patients with COVID-19 compared to patients without COVID-19 [ Time Frame: Day 90 ]
   Survival after 90 days

Biospecimen Retention:   Samples Without DNA

Blood samples

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

All patients with suspected SARS-CoV-2 infection who are admitted to the study centers will be screened for study eligibility according to the inclusion and exclusion criteria.

Criteria

Inclusion Criteria:

• adult patients of every age
• admission to hospital with suspected COVID-19 disease
• confirmed SARS-CoV-2 infection within 48 hours after admission

Exclusion Criteria:

• transferral from another hospital
• other acute central nervous system diseases (e.g. meningoencephalitis, intracerebral ischemia or hemorrhage)
• confirmed SARS-CoV-2 infection later than 48 hours after hospital admission
• participation in another interventional study
• no written informed consent from patient or legal representative

Contacts and Locations

Locations

Germany

Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rostock

Rostock, Mecklenburg-Vorpommern, Germany, D-18057

Sponsors and Collaborators

University of Rostock

Ludwig-Maximilians - University of Munich

University College, London

Investigators

• Principal Investigator: Johannes Ehler, MD; University of Rostock

More Information

• Responsible Party: Dr. Johannes Ehler, MD, PD Dr. med. Johannes Ehler, MD, University of Rostock
• ClinicalTrials.gov Identifier: NCT04359914
• Other Study ID Numbers: COVID-BRAIN
• First Posted: April 24, 2020
• Last Update Posted: May 18, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Delirium; Brain Diseases; Trauma, Nervous System; Critical Illness; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Central Nervous System Diseases; Wounds and Injuries