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The study will be conducted in Dokuz Eylül University Hospital, COVID-19 (Coronavirus Disease 2019) intensive care unit. Three primary conditions will be sought for participants:
In the study, samples will be taken from the liver, kidney, lung, and heart. The samples will be stored in a protective solution and sent to the pathology unit. The examinations will determine the microscopic damage to these organs caused by COVID-19.
Also, the presence of the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) will be investigated by RT-PCR in tissues. The presence of ACE-2 (angiotensin converting enzyme 2) receptor and SARS-CoV-2 nucleoprotein antibody will be investigated by histochemical examination in tissues.
The cases whose treatment resulted in death at Dokuz Eylül University Research and Application Hospital Anesthesiology Intensive Care Unit and whose COVID-19 diagnosis was confirmed by the RT-PCR (real time polymerase chain reaction) test and gave written consent to the inclusion of the patient in the study by a first-degree relative will be included in the study. In the study, samples will be taken from 10 cases in total.
Age, gender, length of hospital stay, respiratory rate at the time of hospitalization, oxygene saturation on ICU admission and Horwitz ratio on ICU admission will be recorded. Also, the comorbidities of these cases, the interpretation of the computed tomography findings performed at the first admission to the hospital in terms of COVID-19, the RT-PCR results routinely sent for COVID-19 examination will be recorded in the case report form. Besides, all medical and supportive treatments applied during the intensive care treatment will be recorded. Liver and kidney function tests, inflammation and coagulation markers, hemoglobin level , and cardiac markers, which are routinely examined at the patient's admission to the intensive care unit, will be recorded.
Postmortem biopsy samples will be performed within 1 hour after the diagnosis of death is confirmed by the patient's doctor. The researchers will perform the procedures in the isolated room prepared for interventional procedures in intensive care. Researchers will wear personal protective equipment (cap, mask, goggles, gloves) before the procedure under the Ministry of Health's instructions.
Biopsy specimens will be taken from the lung, liver, heart, and kidney. Heart, liver, and kidney biopsies were performed as a core biopsy with tru-cut needles under ultrasonography guidance; lung biopsy will be performed by passing through the airway using biopsy forceps.
Each of the biopsy samples will be placed separately in 10 ml of 10% phosphate-buffered formalin solution. The containers will be disinfected with 80% alcohol. It will be placed in a closed zippered bag and kept at room temperature. It will be delivered to the pathology unit after 24 hours. The procedures as tissue cassette, extended tissue tracing, paraffin blocking, sectioning, and hematoxylin-eosin staining will be performed under biosafety level 2 rules in pathology. The cases will be coded as CVDPM-1... (Coronavirus Disease Postmortem 1...). Case report forms will be shared with researchers who will conduct pathological examination over the internet. Informed consent forms received from patients' relatives will be filed in the COVID-19 Intensive Care Unit.
Routine pathology sections will be evaluated in light microscopy according to the following criteria.
Lungs; alveolar epithelial cell damage, hyaline membrane formation, type 2 pneumocyte hyperplasia, diffuse alveolar damage, fibroblastic proliferation, fibrin accumulation, inflammatory infiltration, and the nature of inflammation Liver; lobular lymphocyte infiltration, centrilobular sinusoidal dilatation Kidney; diffuse proximal tubule damage, brushed edge loss, non-isometric vacuolar degeneration, necrosis, hemosiderin, pigmented cast, capillary plugs, vasculitis, intercalary inflammation, hemorrhage, Heart; acute ischemic injury, vascular pathology, inflammation Tissues will be tested for the presence of the SARS-CoV-2 virus by RT-PCR test. ACE2 receptor and SARS-CoV-2 nucleoprotein antibody will be examined by immunohistochemistry.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| COVID-19 group | Other | Liver, lung, heart and kidney biopsies will be performed on each case in the COVID-19 group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liver, lung, heart and kidney biopsy | Procedure | Liver, lung, heart and kidney biopsies will be performed on each case in the COVID-19 group. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The level of histopathological changes | In lung; alveolar epithelial cell damage, hyaline membrane formation, type 2 pneumocyte hyperplasia, diffuse alveolar damage, fibroblastic proliferation, fibrin accumulation, inflammatory infiltration and the nature of inflammation. In liver; lobular lymphocytic infiltration, centrilobular sinusoidal dilatation. In kidney; diffuse proximal tubule damage, brushed edge loss, non-isometric vacuolar degeneration, necrosis, hemosiderin, pigment cast, capillary plugs, vasculitis, interciliary inflammation, hemorrhage. In heart; acute ischemic injury, vascular pathology, inflammation. | in three months after the participant's death |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ali N Gökmen, MD, PhD | Dokuz Eylul University, Department of Anaesthesiology and Reanimation, Division of Intensive Care | Principal Investigator |
| Mehmet N Yakar, MD, PhD | Dokuz Eylul University, Department of Anaesthesiology and Reanimation, Division of Intensive Care | Study Director |
| Safiye Aktaş, MD, PhD | Dokuz Eylul University, Oncology Institute, Department of Basic Oncology | Study Director |
| Bilgin Cömert, MD, PhD | Dokuz Eylul University, Department of Internal Medicine, Division of Intensive Care | Study Director |
| Begüm Ergan, MD, PhD | Dokuz Eylul University, Department of Chest Disease, Division of Intensive Care | Study Director |
| Bişar Ergün, MD, PhD | Dokuz Eylul University, Department of Internal Medicine, Division of Intensive Care | Study Director |
| Fırat Bayraktar, MD, PhD | Dokuz Eylul University, Department of Internal Medicine, Division of Endocrinology and Metabolism | Study Chair |
| Eyüp S Uçan, MD, PhD | Dokuz Eylul University, Department of Chest Disease |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dokuz Eylul University | Izmir | Balçova | 35330 | Turkey (Türkiye) |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D011180 | Postmortem Changes |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D008110 | Liver Extracts |
| ID | Term |
|---|---|
| D014020 | Tissue Extracts |
| D045424 | Complex Mixtures |
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| Aylin Erol | Dokuz Eylul University, Oncology Institute | Study Chair |
| Özde E Gökbayrak | Dokuz Eylul University, Oncology Institute | Study Chair |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002102 | Cadaver |
| D003643 | Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |