Neuropathology in Adults Intensive Care Unit Patients With COVID 19

Study Overview
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Brief Summary
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This is a single center observational autopsy study, conducted during the first wave of the coronavirus disease (COVID-19) pandemic in France. The main objective is to evaluate brain damages in patients who died from COVID-19 to inform the cause of death. Investigations include macroscopic and histology examinations, and virology analyses.

Detailed Description
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Setting: academic center designed as a referral center for patients with COVID-19 Design: single center observational autopsy study Participants: intensive care unit (ICU) adults who died from confirmed COVID-19 during the first wave of the pandemic in France. Oversight: As per legal health authority requirement only patients with suspected or confirmed severe acute respiratory syndrome (SARS)- related to coronavirus 2 infection were admitted to the ICU. The department of pathology and forensic medicine is allowed by legal authority to perform autopsy of non-survivors from COVID-19 to inform the cause of death as per ministerial decree of July 12 2017 and March 28, 2020. In this context, of autopsy for medical purpose and public interest there is no requirement for institutional review board submission. However, consent from patients legal representative or closest relatives is required for autopsy.

Official Title
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A Prospective Observational Autopsy Study of Neuropathology in Adults Intensive Care Unit Patients With COVID 19

Conditions
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COVID 19

Intervention / Treatment
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* Procedure: autopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults admitted to the ICU confirmed COVID-19 died during ICU stay Exclusion Criteria: refusal from patient's legal representative or closest relative

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 non-survivors<br>ICU adults who died from severe COVID-19 and in whom autopsy could be performed | Procedure: autopsy<br>* autopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| detection of severe acute respiratory syndrome related to coronavirus-2 in brain tissues | Specimens treatments Genome detection by real-time reverse transcriptase-polymerase chain reaction and viral culture Next generation sequencing Specimen RNA pre-treatment and evaluation MinION sequencing | From death up to five days | 
| quantification of inflammation, necrosis and hemorrhage in different brain areas | The left hemisphere will be fixed in 10% buffered formalin. Multiple fresh samples will be acquired from different areas of the right hemisphere for freezing. For each frozen sample, a mirror sample of formalin-fixed paraffin-embedded tissue will be taken from the left hemisphere. Samples were fixed with 3.6% glutaraldehyde and embedded in plastic for electron microscopy. Paraffin sections cut to 3-µm thickness will be stained with hematoxylin and eosin stain. Immunohistochemistry will be performed with Clusters of Differentiation 3,4, 20, 68, 138, and glial fibrillary acid protein antibodies on automated immunostainer. Slides will be scanned and analyzed. Electron microscopy will be performed and images will be acquired. | From death up to five days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammation, autopsy, coronavirus, brain