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: 1. Cases whose treatment process resulted in death will be included in the study. 2. The cases must be confirmed with the diagnosis of COVID-19 by the RT-PCR (real time polymerase chain reaction) test. 3. The first-degree relatives must consent for the participation of the subjects in the study by their first-degree relatives. 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.
Procedure: Liver, lung, heart and kidney biopsy
Liver, lung, heart and kidney biopsies will be performed on each case in the COVID-19 group.
Inclusion Criteria:
- Cases 18 years and older than 18 years.
- Cases diagnosed with COVID-19 confirmed by PCR test.
- Cases whose treatment resulted in death.
- Cases that was allowed the participation in the study by signing the informed consent
form by their first degree relatives.
Exclusion Criteria:
- Cases less than 18 years old.
- Cases for which the diagnosis of COVID-19 could not be confirmed.
- Cases for which informed consent could not be obtained.
- Cases whose treatment continues or results in healing.
Dokuz Eylul University
İzmir, Balçova, Turkey