Brain injury is one of the complications in COVID-19 intensive care unit (ICU) survivors,though the precise underlying mechanism is unclear. It is likely caused by a combinationof prolonged hypoxia, a massive systemic inflammatory response, direct infection of thebrain and small vessel vasculitis in combination with widespread hypercoagulopathy andthrombosis. Using novel MRI techniques, blood-brain barrier (BBB) permeability, as wellas other microstructural and microvascular properties of the brain tissue, will beassessed non-invasively in COVID-19 ICU survivors approximately one year after ICUadmission and compared to serial clinical and laboratory measurements of hypercoagulationand inflammation during the (ICU) admission. This study aims to relate factors ofhypercoagulability, inflammation or general illness itself (all during ICU admission) tomicrostructural and microvascular abnormalities on follow-up brain advanced 3T and 7T MRIin COVID-19 ICU survivors. In addition, neuropsychological tests and an objectivesmell/taste test will be used to evaluate neuropsychological status and sense ofsmell/taste. By gaining more insight into the pathogenesis of brain injury, the treatmentof COVID-19 patients in the acute phase might be improved.
Brain injury is one of the complications in COVID-19 intensive care unit (ICU) survivors,
though the precise underlying mechanism is unclear. It is likely caused by a combination
of prolonged hypoxia, a massive systemic inflammatory response, direct infection of the
brain and small vessel vasculitis in combination with widespread hypercoagulopathy and
thrombosis. Using novel MRI techniques, blood-brain barrier (BBB) permeability, as well
as other microstructural and microvascular properties of the brain tissue, will be
assessed non-invasively in COVID-19 ICU survivors approximately 12-24 months after ICU
admission and compared to serial clinical and laboratory measurements of hypercoagulation
and inflammation during the (ICU) admission.
This study aims to relate factors of hypercoagulability, inflammation or general illness
itself (all during ICU admission) to microstructural and microvascular abnormalities on
follow-up brain advanced 3T and 7T MRI in COVID-19 ICU survivors. By gaining more insight
into the pathogenesis of brain injury, the treatment of COVID-19 patients in the acute
phase might be improved.
This is a mono-center follow-up cohort study with measurements at 12-24 months post
hospital discharge. This study will include 70 adults who survived a severe COVID-19
infection for whom ICU admission was necessary during the second/third COVID wave (period
October 2020- ongoing). These patients will be recruited from the MaastrICCht cohort from
the Department of Intensive Care (MUMC+).
Patients will undergo an MRI scan (3T) and optionally a second MRI scan (7T) of
approximately 60 minutes each. These scans will lead to insights in microstructural and
microvascular abnormalities, BBB impairment, and in possible effects of a severe COVID-19
infection on the brainstem and the glymphatic system. In addition to the MRI
measurements, blood samples will be drawn (approximately 20ml) to evaluate ICU follow-up
levels of hypercoagulation and inflammation biomarkers. Follow-up short
neuropsychological tests and two short questionnaires will be used to assess cognitive,
neurological, olfaction and functional status. A brief objective smell and taste testing
will be done to get an objective measure of sense of smell and taste.
By gaining more insight into the pathogenesis of brain injury, the treatment of COVID-19
patients in the acute phase might be improved.
Inclusion Criteria:
- Proven COVID-19 infection for which participant was admitted to the ICU for at least
3 days
- Included in the MaastrICCht cohort (a large database of serial measurements
collected during ICU stay from patients with COVID-19 admitted to the ICU in the
Maastricht University Medical Center+)
- Informed consent is given
- Sufficient command of the Dutch language to follow test instructions and understand
the information letter, informed consent, and questionnaires
Exclusion Criteria:
- Objective cognitive impairments before hospital admission for the COVID-19 infection
- An unexpected incident leading to severe neurological damage after hospital
discharge (such as stroke or traumatic brain injury)
- Contra-indications for MRI scanning (e.g. metal implants, cardiac pacemaker,
claustrophobia, pregnancy, and tattoos in the head/neck region)
- Unwillingness to be informed about clinical relevant (abnormal) MRI-findings
- Contra-indications for a gadolinium-based MRI contrast agent (known allergy or
insufficient kidney function determined by an eGFR < 30 mL/min)
- Physical inability to travel to one of the locations (e.g. bedridden patients)
Maastricht University Medical Center+
Maastricht, Limburg, Netherlands
Marcel JH Ariës, PhD/MD, Principal Investigator
Maastricht University Medical Center