Minimal Invasive Autopsies to Investigate Changes in Deceased COVID-19 Patients

Study Overview
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Brief Summary
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Rationale In a very short time corona virus disease 2019 (COVID-19) has become a pandemic with high morbidity and mortality. The main cause of death is respiratory failure including acute respiratory distress syndrome, however the exact mechanisms and other underlying pathology is currently not yet known. In the current setting of the COVID-19 pandemic complete autopsies seem too risky due to the risk of SARS CoV-2 transmission. Yet, as so little is known, additional histopathological, microbiological and virologic study of tissue of deceased COVID-19 patients will provide important clinical and pathophysiological information. Minimal invasive autopsy combined with postmortem imaging seems therefore an optimal method combining safety on the one hand yet proving significant information on the other. This study aims to determine the cause of death and attributable conditions in deceased COVID-19 patients. This will be performed using post-mortem CT-scanning plus CT-guided MIA to obtain tissue for further histological, microbiological and pathological diagnostics. In addition, the pathophysiology of COVID-19 will be examined by further tissue analysis.

Official Title
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Increasing Our Understanding of COVID-19: Minimal Invasive Autopsies to Investigate Clinical, Radiological, Microbiological and Histopathological Changes in Deceased COVID-19 Patients

Conditions
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COVID-19

Intervention / Treatment
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* Procedure: CT-scan with minimal invasive autopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients with COVID-19 that die during hospitalization in Jessa hospital. COVID-19 is defined as either a positive SARS CoV-2 PCR result OR a high clinical suspicion combined with typical radiologic findings in the absence of an alternative explanation for the clinical picture. Exclusion Criteria: None
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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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: CT-scan with minimal invasive autopsy|CT-guided biopsies will be performed directly following the diagnostic CT-scan. Biopsies will be taken from heart, liver, lungs, spleen, kidneys and abdominal fat according to a standard operation procedure. Biopsies will be taken for further histological examination and storage in the biobank. Of the lung, additional samples will be taken for microbiological examination. Additional samples will be taken in case of (focal) abnormalities on CT-imaging. In case of pleural, cardiac or abdominal fluid, this will be aspirated for further cytological, biochemical and microbiological examination. Finally, 15 cc blood will be drawn from the heart.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of cause of death and contributing factors based on clinical, radiological, microbiological and histopathological data of the deceased patient | For each individual patient the cause of death and contributing factors will be assessed. For each individual these diagnoses will be made during a meeting of a multidisciplinary team consisting of at least an infectious diseases physician, a radiologist and a pathologist. On a case to case basis, additional medical specialists can be asked to attend, including an intensive care specialist, a geriatrician and/or a microbiologist. During the meetings, the clinical, radiological, microbiological and histopathological data will be presented to all attending specialists. The final diagnoses will be based on consensus. Outcomes will be reported as proportions with a 95% confidence interval. | up to one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detailed description of the postmortem radiological changes induced by COVID-19 | The radiological findings will be systematically scored as absent or present. These findings will be reported as proportions with a 95% confidence interval. | up to one month | 
| Detailed description of the postmortem histopathological changes induced by COVID-19 | On the basis of clinical observations at this moment in time correlations will be done between the renal histology findings of the patients with and without renal failure at death as well as between the cardiac histology findings of the patients with and without clinical signs of myocarditis. However, in the light of continuous clinical observations and new insights, this may be expanded in the future. Outcomes will be reported as proportions with a 95% confidence interval. | up to one month | 
| Postmortem quantity of viral RNA | Describe the quantity of viral RNA in the different tissues and relate this to the clinical, radiological and histopathological findings. | up to one month | 
| Postmortem disease mechanisms at cellular level | Study in detail the disease mechanisms at cellular level (including ACE-2 receptor expression in relation to quantity of viral RNA) in the different tissues. | up to one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, cause of death, pathophysiology