Neurological Outcome After SARS-CoV-2 Infection

Study Overview
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Brief Summary
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Wider research context: Since the recognition of SARS-CoV-2 outbreak in 2019, there are now over 126 million COVID-19 cases worldwide with more than 2.7 million deaths. Reports on neurological manifestations vary in prevalence rates (6-84%) and range from mild (headache, hyposmia, myalgia) to severe (encephalopathy, strokes, seizures). Little is known about long-term neurological outcomes of COVID-19 patients. The investigators propose a structured protocol to capture persistent and delayed neurological manifestations, neurocognitive deficits and quality of life (QoL) 3 and 12 months after COVID-19. Objectives: The investigators hypothesize that neurological manifestations and neuropsychological/cognitive deficits can be detected after COVID-19, substantially impact on patients' QoL and can be correlated with structural neuroimaging findings. Main objectives are to assess firstly long-term prevalence rates and natural history of neurological manifestations, secondly neuropsychological/cognitive deficits after COVID-19, thirdly the impact of COVID-19 on measures of mental health, QoL and functional outcome, fourthly to correlate neurological manifestations and distinct neurocognitive deficits with structural MRI abnormalities, and Fifthly to compare these results to age- and sex matched controls hospitalized with pneumonia (Cpneum) and to healthy controls for MRI-data (Chealthy). Approach: The investigators aim to enrol at least 225 patients with COVID-19, in addition to 50 Cpneum and 80 Chealthy. COVID-19 patients will include (group Oóne) outpatients presenting to the hospital, (group two) in-patients not requiring ICU admission, and (group three) patients admitted to the ICU. The investigators will not include asymptomatic patients, patients not presenting to the hospital, and those who do not consent to participate. The standardized protocol includes a firstly a structured neurological examination, secondly olfactory testing, thirdly assessment of QoL, mental health and functional outcome at 3 and 12 months, and fourthly screening for cognitive deficits (at 3 months) and a structured neuropsychological testing (at 12 months) in COVID-19 patients and controls. In a subset of at least 120 COVID-19 patients and 50 controls (Cpneum) high field MRI will be performed at 3 and 12 months. Innovation: The investigators aim to quantify COVID-19 related and specific neurological manifestations and their impact on the individual health condition. The novelty lies in the prospective design, the longitudinal follow-up including and the inclusion of a control group which allows us to explore the natural history of COVID-19 related neurological manifestations. Preliminary analysis of our ongoing 3-month follow-up suggests persistent neurological manifestations and a significant impact of COVID-19 on mental health, cognition and QoL. The investigators believe that our study results likely influence the long-term care of COVID-19 patients and help to identify those, who need further neuro-rehabilitative support

Official Title
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Long-term Neurological Outcome After SARS-CoV-2 Infection

Conditions
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SARS-CoV-2, Post-acute COVID-19 Syndrome

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Patients of either sex, aged ≥18 years with (2) confirmed SARS-CoV-2 infection (according to the Austrian Federal Ministry of Social Affairs, Health, Care and Consumer Protection), (3) signed and dated declaration of consent by the patient according to ICH-GCP Guidelines, (4) being able to speak and understand the German language Exclusion Criteria: (1) Pre-existing dementia, (2) confirmed pregnancy, (3) patients without the capacity to consent, (4) asymptomatic patients, (5) patients not presenting to the hospital Specific Inclusion/exclusion criteria for the MRI substudy Inclusion criteria: (1) Patients of either sex, aged ≥18 years with (2) confirmed SARS-CoV-2 infection (according to the Austrian Federal Ministry of Social Affairs, Health, Care and Consumer Protection), (3) signed and dated declaration of consent by the patient according to ICH-GCP Guidelines, (4) being able to speak and understand the German language (5) agree to participate for MRI Exclusion criteria: (1) Pre-existing dementia, (2) confirmed pregnancy, (3) patients without the capacity to consent, (4) asymptomatic patients, (5) patients not presenting to the hospital (6) definite contraindication to MRI (e.g. pacemakers) Controls Patients after pneumonia (Cpneum) We will enrol at least 50 hospitalized age- and sex matched patients with pneumonia based on disease severity during the acute disease as: (group One) hospitalized (moderate; n=25) and (group two) severe patients admitted to the ICU for mechanical ventilation (n=25). Inclusion criteria: (1) Patients of either sex, aged ≥18 years with (2) bacterial pneumonia according to CDC criteria, (3) signed and dated declaration of consent by the patient according to ICH-GCP Guidelines, and (4) being able to speak and understand the German language, (5) agree to participate for MRI Exclusion criteria: (1) Pre-existing dementia, (2) confirmed pregnancy, (3) patients without the capacity to consent, (4) definite contraindication to MRI (e.g. pacemakers) Healthy referents (Chealthy) Currently n=38 MRI acquisitions of prospectively recruited healthy individuals are available, fulfilling the criteria of this proposal (age- and sex matched; same MR protocol). This cohort will be prospectively extended by n=42 to reach age and sex matched criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| C healthy<br>Healthy control group | Other: No Intervention<br>* No Intervention takes place, Patients are being observed and classified according to disease severity<br>* Other names: Observation;|
| C pneum<br>Control group of patients who were hospitalised and diagnosed with pneumonia ( COVID-19 pneumonia excluded) | Other: No Intervention<br>* No Intervention takes place, Patients are being observed and classified according to disease severity<br>* Other names: Observation;|
| Mild<br>Outpatients presenting to the hospital with COVID-19 | Other: No Intervention<br>* No Intervention takes place, Patients are being observed and classified according to disease severity<br>* Other names: Observation;|
| Moderate<br>In-patients with COVID-19 not requiring ICU admission | Other: No Intervention<br>* No Intervention takes place, Patients are being observed and classified according to disease severity<br>* Other names: Observation;|
| Severe<br>Patients with COVID-19 admitted to the ICU | Other: No Intervention<br>* No Intervention takes place, Patients are being observed and classified according to disease severity<br>* Other names: Observation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of neurological manifestations in COVID-19 patients | 3-month prevalence of neurological manifestations in COVID-19 patients presenting to the hospital in comparison to control patients (Cpneum) | 3-months | 
| Prevalence of neurological manifestations in COVID-19 patients | 12-month prevalence of neurological manifestations in COVID-19 patients presenting to the hospital in comparison to control patients (Cpneum) | 12-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association, prevalence and classification of neurologic manifestations with structural neuroimaging in hospitalised COVID-19 patients after 3-months. | Association of neurologic manifestations (specifically neuropsychological deficits and smelling deficits) with structural neuroimaging (high-field MRI) in comparison to control patients (Cpneum). Prevalence and classification of neuroimaging abnormalities in hospitalized COVID-19 patients in comparison to controls (Cpneum and Chealthy). Other (exploratory) endpoints derived from the clinical database might be analyzed on data driven considerations 3-months after acute disease. | 3-months | 
| Association, prevalence and classification of neurologic manifestations with structural neuroimaging in hospitalised COVID-19 patients after 12-months. | Association of neurologic manifestations (specifically neuropsychological deficits and smelling deficits) with structural neuroimaging (high-field MRI) in comparison to control patients (Cpneum). Prevalence and classification of neuroimaging abnormalities in hospitalized COVID-19 patients in comparison to controls (Cpneum and Chealthy). Other (exploratory) endpoints derived from the clinical database might be analyzed on data driven considerations 12-months after acute disease. | 12-months |