Praktische Aspekte von COVID-19-Obduktionen

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Abstract

Hintergrund

Die COVID-19-Pandemie stellt die medizinische Fachwelt vor eine bislang ungekannte Herausforderung. Obduktionen sind für die Erforschung dieser neuen Krankheit wesentlich, ihre sichere Durchführbarkeit wurde aber anfangs infrage gestellt.

Fragestellung

Unter welchen rechtlichen Rahmenbedingungen und unter welchen Schutzmaßnahmen können COVID-19-Obduktionen durchgeführt werden?

Material und Methoden

Das obduktionstechnische Vorgehen in 5 Zentren in Deutschland, Österreich und der Schweiz wird unter Berücksichtigung der jeweiligen rechtlichen Grundlagen und der ergriffenen Schutzmaßnahmen dargestellt.

Ergebnisse

In allen Institutionen konnten die Obduktionen in technisch geeigneten Räumen sicher durchgeführt werden. Die persönliche Schutzausrüstung umfasste Augenschutz, Mund-Nasen-Masken (mindestens FFP2), Kopfhauben, Funktionskleidung, Mäntel, Schürzen und 2 Paar Handschuhe. In 4 Instituten wurden die Leichen nach unterschiedlichen Techniken eröffnet. In einem Institut wurde ein minimal-invasives Verfahren, die postmortale ultraschallunterstützte Gewebeentnahme im Rahmen des „postmortal imaging and biopsy programs“, durchgeführt. Letztere gibt zwar keine makroskopischen Einblicke in die inneren Organe, ermöglicht aber eine standardisierte bioptische Gewinnung von Gewebe für Diagnostik und Forschung. Aus den Obduktionen resultierten mehrere Arbeiten in hochrangigen Journalen, die profunde Einblicke in die Organveränderungen ermöglichten und wesentliche Schlüsse auf die Pathomechanismen zuließen. Virus-RNA konnte häufig in COVID-19-Verstorbenen nachgewiesen werden. Vereinzelt gelang auch die Anzüchtung der Viren. Die Frage nach der postmortalen Infektiosität bleibt aber unklar und bei Ct-Werten über 30 umstritten.

Fazit

Unter Beachtung geeigneter Schutzmaßnahmen sind Obduktionen von COVID-19-Verstorbenen sicher durchführbar und für die medizinische Forschung hoch relevant.

Zusatzmaterial online

Zusätzliche Informationen sind in der Online-Version dieses Artikels (10.1007/s00292-021-00925-w) enthalten.

Translated abstract

Background

The COVID-19 pandemic represents a so far unknown challenge for the medical community. Autopsies are important for studying this disease, but their safety was challenged at the beginning of the pandemic.

Objectives

To determine whether COVID-19 autopsies can be performed under existing legal conditions and which safety standards are required.

Materials and methods

The autopsy procedure undertaken in five institutions in Germany, Austria, and Switzerland is detailed with respect to legal and safety standards.

Results

In all institutions the autopsies were performed in technically feasible rooms. The personal equipment consisted of functional clothing including a disposable gown and apron, a surgical cap, eye protection, FFP‑3 masks, and two pairs of gloves. In four institutions, complete autopsies were performed; in one institution the ultrasound-guided biopsy within the postmortal imaging and biopsy program. The latter does not allow the appreciation of gross organ pathology; however, it is able to retrieve standardized biopsies for diagnostic and research purposes. Several scientific articles in highly ranked journals resulted from these autopsies and allowed deep insights into organ damage and conclusions to better understand the pathomechanisms. Viral RNA was frequently detectable in the COVID-19 deceased, but the issue of infectivity remains unresolved and it is questionable if Ct values are greater than 30.

Conclusions

With appropriate safeguards, autopsies of people who have died from COVID-19 can be performed safely and are highly relevant to medical research.

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Most cited references 31

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Endothelial cell infection and endotheliitis in COVID-19

Zsuzsanna Varga, Andreas J. Flammer, Peter Steiger … (2020)

Cardiovascular complications are rapidly emerging as a key threat in coronavirus disease 2019 (COVID-19) in addition to respiratory disease. The mechanisms underlying the disproportionate effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities, however, remain incompletely understood.1, 2 SARS-CoV-2 infects the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is expressed in several organs, including the lung, heart, kidney, and intestine. ACE2 receptors are also expressed by endothelial cells. 3 Whether vascular derangements in COVID-19 are due to endothelial cell involvement by the virus is currently unknown. Intriguingly, SARS-CoV-2 can directly infect engineered human blood vessel organoids in vitro. 4 Here we demonstrate endothelial cell involvement across vascular beds of different organs in a series of patients with COVID-19 (further case details are provided in the appendix). Patient 1 was a male renal transplant recipient, aged 71 years, with coronary artery disease and arterial hypertension. The patient's condition deteriorated following COVID-19 diagnosis, and he required mechanical ventilation. Multisystem organ failure occurred, and the patient died on day 8. Post-mortem analysis of the transplanted kidney by electron microscopy revealed viral inclusion structures in endothelial cells (figure A, B ). In histological analyses, we found an accumulation of inflammatory cells associated with endothelium, as well as apoptotic bodies, in the heart, the small bowel (figure C) and lung (figure D). An accumulation of mononuclear cells was found in the lung, and most small lung vessels appeared congested. Figure Pathology of endothelial cell dysfunction in COVID-19 (A, B) Electron microscopy of kidney tissue shows viral inclusion bodies in a peritubular space and viral particles in endothelial cells of the glomerular capillary loops. Aggregates of viral particles (arrow) appear with dense circular surface and lucid centre. The asterisk in panel B marks peritubular space consistent with capillary containing viral particles. The inset in panel B shows the glomerular basement membrane with endothelial cell and a viral particle (arrow; about 150 nm in diameter). (C) Small bowel resection specimen of patient 3, stained with haematoxylin and eosin. Arrows point to dominant mononuclear cell infiltrates within the intima along the lumen of many vessels. The inset of panel C shows an immunohistochemical staining of caspase 3 in small bowel specimens from serial section of tissue described in panel D. Staining patterns were consistent with apoptosis of endothelial cells and mononuclear cells observed in the haematoxylin-eosin-stained sections, indicating that apoptosis is induced in a substantial proportion of these cells. (D) Post-mortem lung specimen stained with haematoxylin and eosin showed thickened lung septa, including a large arterial vessel with mononuclear and neutrophilic infiltration (arrow in upper inset). The lower inset shows an immunohistochemical staining of caspase 3 on the same lung specimen; these staining patterns were consistent with apoptosis of endothelial cells and mononuclear cells observed in the haematoxylin-eosin-stained sections. COVID-19=coronavirus disease 2019. Patient 2 was a woman, aged 58 years, with diabetes, arterial hypertension, and obesity. She developed progressive respiratory failure due to COVID-19 and subsequently developed multi-organ failure and needed renal replacement therapy. On day 16, mesenteric ischaemia prompted removal of necrotic small intestine. Circulatory failure occurred in the setting of right heart failure consequent to an ST-segment elevation myocardial infarction, and cardiac arrest resulted in death. Post-mortem histology revealed lymphocytic endotheliitis in lung, heart, kidney, and liver as well as liver cell necrosis. We found histological evidence of myocardial infarction but no sign of lymphocytic myocarditis. Histology of the small intestine showed endotheliitis (endothelialitis) of the submucosal vessels. Patient 3 was a man, aged 69 years, with hypertension who developed respiratory failure as a result of COVID-19 and required mechanical ventilation. Echocardiography showed reduced left ventricular ejection fraction. Circulatory collapse ensued with mesenteric ischaemia, and small intestine resection was performed, but the patient survived. Histology of the small intestine resection revealed prominent endotheliitis of the submucosal vessels and apoptotic bodies (figure C). We found evidence of direct viral infection of the endothelial cell and diffuse endothelial inflammation. Although the virus uses ACE2 receptor expressed by pneumocytes in the epithelial alveolar lining to infect the host, thereby causing lung injury, the ACE2 receptor is also widely expressed on endothelial cells, which traverse multiple organs. 3 Recruitment of immune cells, either by direct viral infection of the endothelium or immune-mediated, can result in widespread endothelial dysfunction associated with apoptosis (figure D). The vascular endothelium is an active paracrine, endocrine, and autocrine organ that is indispensable for the regulation of vascular tone and the maintenance of vascular homoeostasis. 5 Endothelial dysfunction is a principal determinant of microvascular dysfunction by shifting the vascular equilibrium towards more vasoconstriction with subsequent organ ischaemia, inflammation with associated tissue oedema, and a pro-coagulant state. 6 Our findings show the presence of viral elements within endothelial cells and an accumulation of inflammatory cells, with evidence of endothelial and inflammatory cell death. These findings suggest that SARS-CoV-2 infection facilitates the induction of endotheliitis in several organs as a direct consequence of viral involvement (as noted with presence of viral bodies) and of the host inflammatory response. In addition, induction of apoptosis and pyroptosis might have an important role in endothelial cell injury in patients with COVID-19. COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19. This hypothesis provides a rationale for therapies to stabilise the endothelium while tackling viral replication, particularly with anti-inflammatory anti-cytokine drugs, ACE inhibitors, and statins.7, 8, 9, 10, 11 This strategy could be particularly relevant for vulnerable patients with pre-existing endothelial dysfunction, which is associated with male sex, smoking, hypertension, diabetes, obesity, and established cardiovascular disease, all of which are associated with adverse outcomes in COVID-19.

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Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

Maximilian Ackermann, Stijn Verleden, Mark Kuehnel … (2020)

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.

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Autopsy Findings and Venous Thromboembolism in Patients With COVID-19

Dominic Wichmann, Jan-Peter Sperhake, Marc Lütgehetmann … (2020)

Background: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. Objective: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. Design: Prospective cohort study. Setting: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. Patients: The first 12 consecutive COVID-19–positive deaths. Measurements: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. Limitation: Limited sample size. Conclusion: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. Primary Funding Source: University Medical Center Hamburg-Eppendorf.

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Author and article information

Contributors

Bruno Märkl: bruno.maerkl@uka-science.de

Journal

Journal ID (nlm-ta): Pathologe

Journal ID (iso-abbrev): Pathologe

Title: Der Pathologe

Publisher: Springer Medizin (Heidelberg )

ISSN (Print): 0172-8113

ISSN (Electronic): 1432-1963

Publication date (Electronic): 24 February 2021

Pages: 1-11

Affiliations

[1 ]GRID grid.1957.a, ISNI 0000 0001 0728 696X, Institut für Pathologie, Universitätsklinikum Aachen, , RTWH Aachen, ; Aachen, Deutschland

[2 ]GRID grid.411668.c, ISNI 0000 0000 9935 6525, Institut für Pathologie, , Universitätsklinikum Erlangen, ; Erlangen, Deutschland

[3 ]GRID grid.5110.5, ISNI 0000000121539003, Institut für Pathologie, , Landeskrankenhaus Graz II, Akademisches Lehrkrankenhaus der Medizinischen Universität Graz, ; Graz, Österreich

[4 ]GRID grid.9970.7, ISNI 0000 0001 1941 5140, Medizinische Fakultät, , Johannes-Kepler-Universität Linz, ; Linz, Österreich

[5 ]GRID grid.7307.3, ISNI 0000 0001 2108 9006, Allgemeine und Spezielle Pathologie, Medizinische Fakultät, , Universität Augsburg, ; Augsburg, Deutschland

[6 ]GRID grid.6612.3, ISNI 0000 0004 1937 0642, Institut für Medizinische Genetik und Pathologie, Universitätsspital Basel, , Universität Basel, ; Basel, Schweiz

[7 ]GRID grid.6936.a, ISNI 0000000123222966, Institut für Pathologie und pathologische Anatomie, , Technische Universität München, ; München, Deutschland

[8 ]GRID grid.419801.5, ISNI 0000 0000 9312 0220, Institut für Pathologie und Molekulare Diagnostik, , Universitätsklinikum Augsburg, ; Stenglinstr. 2, 86156 Augsburg, Deutschland

Author notes

[Schwerpunktherausgeber]

W. Roth, Mainz

P. Boor, Aachen

Article

Publisher ID: 925

DOI: 10.1007/s00292-021-00925-w

PMC ID: 7903213

PubMed ID: 33625535

SO-VID: a4770328-2113-42a5-8c1b-54a497117042

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

Praktische Aspekte von COVID-19-Obduktionen Translated title: Practical aspects of COVID-19 autopsies

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Abstract

Hintergrund

Fragestellung

Material und Methoden

Ergebnisse

Fazit

Zusatzmaterial online

Translated abstract

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 31

Endothelial cell infection and endotheliitis in COVID-19

Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19

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