Minimally invasive autopsies for the investigation of pulmonary pathology of COVID-19—experiences of a longitudinal series of 92 patients

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Abstract

Minimally invasive autopsies (MIAs) allow the collection of tissue samples for diagnostic and research purposes in special situations, e.g., when there is a high risk of infection which is the case in the context of COVID-19 or restrictions due to legal or personal reasons. We performed MIA to analyze lung tissue from 92 COVID-19 patients (mean age 78 years; range 48–98; 35 women, 57 men), representing 44% of all patients who died from the disease between October 2020 and April 2021. An intercostal approach was used with removal of a 5-cm rib section followed by manual collection of four lung tissue samples (5–8 cm in size). Diffuse alveolar damage (DAD) was found in 89 (97%) patients at various stages. Exudative DAD (eDAD) predominated in 18 (20%) patients, proliferative DAD (pDAD) in 43 (47%) patients, and mixed DAD (mDAD) in 31 (34%) patients. There were no significant differences in the predominant DAD pattern between tissue samples from the same patient. Additional purulent components were present in 46 (50%) cases. Fungi were detected in 11 (12%) patients. The pDAD pattern was associated with longer hospital stay including intensive care unit ( p=0.026 and p<0.001) and younger age ( p=0.019). Positive bronchoalveolar lavage and blood cultures were observed more frequently in pDAD patterns ( p<0.001; p=0.018). In contrast, there was no significant association between intravital positive microbiological results and superimposed bronchopneumonia or fungal infection at autopsy. Having demonstrated the characteristic lung changes in a large longitudinal autopsy series, we conclude that the presented MIA approach can be considered a reliable and safe method for performing post mortem lung diagnostics in COVID-19 and other high-risk situations. The lack of correlation between histological changes indicative of bacterial or fungal superinfection and microbiology could have clinical implications for disease and treatment surveillance.

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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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Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study

Luca Carsana, Aurelio Sonzogni, Ahmed Nasr … (2020)

Summary Background COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes. Methods We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation. Findings All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet–fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes. Interpretation The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet–fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy. Funding None.

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Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series

Sigurd Lax, Kristijan Skok, Peter Michael Zechner … (2020)

Background: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. Objective: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. Design: Prospective autopsy study. Setting: Single pathology department. Participants: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). Measurements: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. Results: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. Limitation: The sample was small. Conclusion: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. Primary Funding Source: None.

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Author and article information

Contributors

Rupert Langer:

ORCID: http://orcid.org/0000-0001-9491-3609

rupert.langer@kepleruniklinikum.at

Journal

Journal ID (nlm-ta): Virchows Arch

Journal ID (iso-abbrev): Virchows Arch

Title: Virchows Archiv

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0945-6317

ISSN (Electronic): 1432-2307

Publication date (Electronic): 1 September 2023

Publication date PMC-release: 1 September 2023

Publication date (Print): 2023

Volume: 483

Issue: 5

Pages: 611-619

Affiliations

[1 ]GRID grid.473675.4, Institute of Clinical Pathology, Kepler University Hospital, ; Krankenhausstr. 9, 4021 Linz, Austria

[2 ]GRID grid.9970.7, ISNI 0000 0001 1941 5140, Medical Faculty, , Johannes Kepler University, ; Linz, Austria

[3 ]GRID grid.473675.4, Division of Infectious Diseases and Tropical Medicine, Department of Pulmonary Medicine, , Kepler University Hospital, ; Linz, Austria

[4 ]Ignaz-Semmelweis-Institute, Interuniversity Institute for Infection Research, Vienna, Austria

[5 ]GRID grid.473675.4, Department of Anesthesiology and Intensive Care Medicine, , Kepler University Hospital, ; Linz, Austria

[6 ]GRID grid.473675.4, Department of Pulmonary Medicine, , Kepler University Hospital, ; Linz, Austria

[7 ]GRID grid.473675.4, Department of Hematology and Medical Oncology, , Kepler University Hospital, ; Linz, Austria

Author information

Rupert Langer http://orcid.org/0000-0001-9491-3609

Article

Publisher ID: 3622

DOI: 10.1007/s00428-023-03622-6

PMC ID: 10673967

PubMed ID: 37653260

SO-VID: e5060b52-7739-4212-a759-aac334f125c1

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 24 January 2023

Date revision received : 20 July 2023

Date accepted : 7 August 2023

Funding

Funded by: Johannes Kepler University Linz

Open Access :

Open access funding provided by Johannes Kepler University Linz.

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ScienceOpen disciplines: Pathology

Keywords: minimally invasive autopsy,pulmonary pathology,diffuse alveolar damage,covid-19

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ScienceOpen disciplines: Pathology

Keywords: minimally invasive autopsy, pulmonary pathology, diffuse alveolar damage, covid-19

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Minimally invasive autopsies for the investigation of pulmonary pathology of COVID-19—experiences of a longitudinal series of 92 patients

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Novel Coronavirus Disease COVID-19

Most cited references 48

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19

Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study

Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series

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