Neurocognitive Impairment in Patients With COVID-19 (NCoV)

Biomarker-guided Assessment of Neurocognitive Impairment in Patients With COVID-19 - a Multicenter Case-control Study

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Delirium; Critical Illness; Encephalopathy; Central Nervous System Injury

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 Type: Observational
• Enrollment (Actual): 118

Contacts and Locations

Study Locations

• Germany
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, D-18057
      • Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rostock

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life in patients with COVID-19 compared to patients without COVID-19 after hospital discharge	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)]	Day 90
Length of hospital stay in patients with COVID-19 compared to patients without COVID-19	Cumulative days in hospital	1 year
90-day survival in patients with COVID-19 compared to patients without COVID-19	Survival after 90 days	Day 90

Collaborators and Investigators

• Sponsor: University of Rostock
• Collaborators: University College, London; Ludwig-Maximilians - University of Munich
• Investigators: Principal Investigator: Johannes Ehler, MD, University of Rostock

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: April 19, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Wounds and Injuries; Disease Attributes; COVID-19; Brain Diseases; Critical Illness; Trauma, Nervous System
• Other Study ID Numbers: COVID-BRAIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No