Clinical trial NCT05025839: Neurological Outcome After SARS-CoV-2 Infection
Official title: Long-term Neurological Outcome After SARS-CoV-2 Infection
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: SARS-CoV-2
Post-acute COVID-19 Syndrome
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
First posted: 2021-08-27
Enrollment: 355
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Prevalence of neurological manifestations in COVID-19 patients
timeFrame: 3-months
measure: Prevalence of neurological manifestations in COVID-19 patients
timeFrame: 12-months
Secondary outcomes:
measure: Association, prevalence and classification of neurologic manifestations with structural neuroimaging in hospitalised COVID-19 patients after 3-months.
timeFrame: 3-months
measure: Association, prevalence and classification of neurologic manifestations with structural neuroimaging in hospitalised COVID-19 patients after 12-months.
timeFrame: 12-months
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Department of Neurology
state: Tyrol
Study officials:
References: