Recovery After Critical Covid-19 Infection

Study Overview
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Brief Summary
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The study focuses on the recovery of respiratory, cardiovascular and neurological/neuropsychological recovery after intensive care treatment for covid-19. The results will be compared with those obtained from patients treated in the regular wards for covid-19, persons with home treated covid-19 and non-covid controls.

Detailed Description
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Eligible patients who have been treated in the intensive care units of Helsinki University Hospital are invited to participate. Controls are recruited from follow-up clinics, and with announcements in media and websites. The participants receive an invitation to a follow-up clinic where their experiences from the ICU treatment and recovery will be discussed. The investigators will perform neuropsychologic testing (6 months post-discharge), a telephone interview (3 months) and send written questionnaires (3, 6 and 24 months) to the participants. The participants will undergo MRI imaging of the brain and laboratory tests will be taken. The olfactory function will be tested at a follow-up clinic. Data on the patients´ respiratory function from clinical spirometry and diffusion capacity testing 3 and 6 months after discharge are collected. The patients will perform a 6 min walk test. Data on coagulation laboratory values will be registered from acute phase and 6 months after discharge. The investigators will also analyse ApoE alleles, neurofilament light and NAD-metabolites and study their correlation with neuropsychologic findings and long term symptoms (up to 5 years after hospital discharge). Participants will also undergo magnetic resonance imaging of the heart at 6-12 months after the hospital discharge, and laboratory samples, a symptom questionnaire and electrocardiogram are collected. Inflammatory parameters and variables associated with regulating inflammation and coagulation will be analysed. Clinical data from the acute and post-acute phase and demographic data are collected from the patient data management systems. The target patient number is 75 intensive care treated patients and 50 control persons in each three control group.

Official Title
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Recovery After Critical Covid-19 Infection

Conditions
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Covid-19

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-100 Positive PCR for Sars-CoV-2 (except non-covid controls, who must be negative) Native language Finnish or Swedish Informed consent to study to study participation Exclusion Criteria: Age under 18 Pregnant or lactating Major neurologic diagnosis (TBI, dementia, stroke, Parkinson´s disease before covid-19) Substantially impaired hearing or vision Developmental disability. No consent to study participation Contraindication to MR imaging (such as cardiac pacemaker, allergy to contrast)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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 |
| --- | --- |
| Patients: ICU treated covid-19 patients<br>Neuropsychologic testing Respiratory function testing, chest x-ray and 6 minute walk test MRI of the brain and heart Laboratory tests Olfactory function tests Neuropsychology questionnaires | |
| Control group 1, covid-19 patients treated in the regular wards<br>As above, without 6 minute walk test or routine chest x-ray | |
| Control group 2, persons with covid-19 without hospitalization<br>As above, but without respiratory testing | |
| Control group 3, non-covid controls<br>As control group 2 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive function 6 months after hospital discharge | Global score calculated from three domains: memory, executive functions and attention.Memory: WMS-III Word list delayed recall + WMS-III Logical memory delayed recall + Rey Complex Figure, delayed recall Executive: TMB (time, reversed) + Stroop interference (time, reversed) + FAB score Attention: WAIS-IV Coding + CPT (correct items) + Stroop naming (time, reversed) The global score will be compared with controls and age matched national references | 6 months after hospital discharge | 
| Diffusion capacity 6 months after hospital discharge | Diffusion capacity DLCO results (percentage of predicted) 6 months after ICU treatment for covid-19 | 6 months after hospital discharge | 
| Incidence of post myocarditis findings in MRI of the heart | Incidence of findings in cardiac MRI indicating previous myocarditis in each group | 6-12 months after hospital discharge | 
| Six minute walk test distance | The distance in meters walked by ICU treated patients in 6 minutes in controlled test environment | 6 months after hospital discharge | 
| Restriction in lung function tests | Restriction in lung function parameters vital capacity and forced vital capacity (z-scores) in measured by spirometry | 6 months after hospital discharge | 
| Cerebral microbleeds | Number and anatomical distribution of cerebral microbleeds in MRI imaging of the brain | 6 months after hospital discharge | 
| Plasma matrix metalloproteinases -8, -9 and TIMP-1 6 months after hospital discharge | Plasma matrix metalloproteinases -8, -9 and TIMP-1 levels in ng/mL 6 months after hospital discharge | 6 moths after hospital discharge | 
| Plasma neurofilament level and its correlation with global score in neuropsychological test battery | Plasma neurofilament level and its correlation with global score in neuropsychological test battery | 6 months after hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation ApoE 4 alleles with disease severity | Laboratory analysis of ApoE alleles and comparison of their frequencies among groups | 6 months post-covid | 
| Correlation of cerebral microbleeds with neuropsychological global score | Correlation of type and location of cerebral microbleeds with neuropsychological global score | 6 moths after hospital discharge | 
| Association of the incidence of cerebral microbleeds with findings in cardiac MRI | Association of the incidence of cerebral microbleeds with findings in cardiac MRI | 6-12 months after hospital discharge | 
| Correlation of plasma neurofilament with cerebral microbleeds | Correlation of plasma neurofilament with cerebral microbleeds in brain MR imaging | 6 months after hospital discharge | 
| Correlation of 6 minute walk test heart rate variables with cardiac function | Correlation of heart rate in rest, exercise and 5 minutes after exercise with cardiac output measured in heart MRI | 6-12 months after hospital discharge | 
| Correlation of matrix metalloproteinase 9 with diffusion capacity | Correlation of matrix metalloproteinase 9 (ng/mL) with lung diffusion capacity z-score | 6 months after hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post-traumatic stress, intensive care unit, cognitive function, delirium