Neurocognitive Impairment in Patients With COVID-19

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Critical Illness, COVID-19, Central Nervous System Injury, Delirium, Encephalopathy

Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NCoV-A-COVID<br>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<br>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<br>pediatric patients admission to hospital with suspected COVID-19 disease confirmed SARS-CoV-2 infection within 48 hours after admission | |
| NCoV-P-CONTROL<br>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?
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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 |