Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study

Dominic Wichmann, Jan-Peter Sperhake, Marc Lütgehetmann, Stefan Steurer, Carolin Edler, Axel Heinemann, Fabian Heinrich, Herbert Mushumba, Inga Kniep, Ann Sophie Schröder, Christoph Burdelski, Geraldine de Heer, Axel Nierhaus, Daniel Frings, Susanne Pfefferle, Heinrich Becker, Hanns Bredereke-Wiedling, Andreas de Weerth, Hans-Richard Paschen, Sara Sheikhzadeh-Eggers, Axel Stang, Stefan Schmiedel, Carsten Bokemeyer, Marylyn M Addo, Martin Aepfelbacher, Klaus Püschel, Stefan Kluge, Dominic Wichmann, Jan-Peter Sperhake, Marc Lütgehetmann, Stefan Steurer, Carolin Edler, Axel Heinemann, Fabian Heinrich, Herbert Mushumba, Inga Kniep, Ann Sophie Schröder, Christoph Burdelski, Geraldine de Heer, Axel Nierhaus, Daniel Frings, Susanne Pfefferle, Heinrich Becker, Hanns Bredereke-Wiedling, Andreas de Weerth, Hans-Richard Paschen, Sara Sheikhzadeh-Eggers, Axel Stang, Stefan Schmiedel, Carsten Bokemeyer, Marylyn M Addo, Martin Aepfelbacher, Klaus Püschel, Stefan Kluge

Abstract

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.

Figures

Figure 1.
Figure 1.
Antemortem versus postmortem computed tomographic imaging (case 3). Top. Contrast medium–enhanced computed tomography scan demonstrates the antemortem findings: bilateral ground glass opacities in the lower lobes of both lungs (yellow asterisks) and a chest tube (yellow arrow), which has been introduced to treat a pneumothorax (yellow arrowheads). Bottom. Computed tomography scan without contrast medium enhancement demonstrates the corresponding postmortem findings. For technical reasons, the postmortem image has a lower resolution. To protect the staff from potential infection, bodies were scanned in a double-layer body bag with the arms positioned alongside the body. Although the findings correspond to the antemortem images, ground glass opacities in both lower lobes (yellow asterisks) and a chest tube (yellow arrow) are seen. In addition, a central venous line (red arrowhead) and gastric tube (red arrow) are visible.
Figure 2.
Figure 2.
Macroscopic autopsy findings. A. Patchy aspect of the lung surface (case 1). B. Cutting surface of the lung in case 4. C. Pulmonary embolism (case 3). D. Deep venous thrombosis (case 5).
Appendix Figure 1.
Appendix Figure 1.
Thrombosis of the prostatic vein (case 1) (arrows).
Figure 3.
Figure 3.
Histopathologic findings. A. Diffuse alveolar damage with hyaline membranes (case 4) (hematoxylin–eosin [H&E] stain; original magnification,×50). B. Hyaline membranes (case 4) (cytokeratin AE1/AE3 stain, original magnification×50). C. Squamous metaplasia in the lung (case 5) (H&E stain; original magnification,×100). D. Pulmonary embolism (case 1) (H&E stain; original magnification,×100).
Appendix Figure 2.
Appendix Figure 2.
Mononuclear infiltrations consisting of lymphocytes (arrows) in the myocardium of the right ventricle (case 3) (hematoxylin–eosin stain; original magnification,×100).

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Source: PubMed

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