Neurological Outcome After SARS-CoV-2 Infection (ATTRACT)

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

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

Study Overview

• Status: Recruiting
• Conditions: SARS-CoV-2; Post-acute COVID-19 Syndrome
• Intervention / Treatment: Other: No Intervention

• Study Type: Observational
• Enrollment (Anticipated): 355

Contacts and Locations

Study Locations

• Austria
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Recruiting
      • Medical University Innsbruck, Department of Neurology
      • Contact: Raimund Helbok, Priv.Doz. Dr.; Phone Number: 81689 +43 50 504; Email: raimund.helbok@tirol-kliniken.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

We aim to include a full dataset of at least 180 patients undergoing 3- and 12-month follow-up. Due to an estimated dropout rate of ~20%, approximately 225 patients are planned to be included in 3-month follow-up. Out of these, we estimate to include a minimum of 50 patients in each of the 3 pre-defined groups, which is feasible based on the preliminary analysis of patient distribution: severe patients: 25%, moderate patients: 50% and mild patients: 25%. In addition, we aim to include at least 120 patients in the MRI sub-study. For the control group, we plan to include 50 age- and sex matched patients (n=25 normal ward, n=25 ICU admission) who undergo the same 3- and 12-month study protocol including MR imaging and neurocognitive testing as COVID-19 patients. Out of these, we expect an estimated dropout rate of ~10% at the 12-month follow-up resulting in 40 patients who will completely finish the study protocol.

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

5

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University Innsbruck

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: August 18, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: KLI 986

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
• product manufactured in and exported from the U.S.: No