Recovery After Critical Covid-19 Infection (RECOVID)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Covid-19

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

Study Locations

• Finland
  • Capital Province Of Finland
    • Helsinki, Capital Province Of Finland, Finland, 00290
      • Helsinki university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who are recovering from critical covid-infection and controls that are either patients recovering from a hospital regular ward treated for covid or covid that has not required hospitalisation. Non-covid controls are age and sex-matched persons (matched to ICU treated group of participants) with no covid-19 in history.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Patients: ICU treated covid-19 patients; 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; As above, without 6 minute walk test or routine chest x-ray
Control group 2, persons with covid-19 without hospitalization; As above, but without respiratory testing
Control group 3, non-covid controls; As control group 2

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Helsinki
• Collaborators: Uppsala University; Göteborg University

Publications and helpful links

General Publications

• Ollila H, Pihlaja R, Koskinen S, Tuulio-Henriksson A, Salmela V, Tiainen M, Hokkanen L, Hastbacka J. Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study. Crit Care. 2022 Jul 20;26(1):223. doi: 10.1186/s13054-022-04092-z.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): July 25, 2024
• Study Completion (Anticipated): July 25, 2024

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: intensive care unit; delirium; cognitive function; post-traumatic stress
• 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: HUS/1949/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No