Postmortem chest computed tomography in COVID-19: A minimally invasive autopsy method

Abstract

Objectives: Performing autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology and pathology to evaluate postmortem CT lung findings and their correlation with histopathology.

Methods: Twenty-nine patients with fatal COVID-19 underwent postmortem chest CT, and multiple lung tissue samples were collected. The chest CT scans were analyzed and quantified according to lung involvement in five categories: normal, ground-glass opacities, crazy-paving, small consolidations, and large or lobar consolidations. The lung tissue samples were examined and quantified in three categories: normal lung, exudative diffuse alveolar damage (DAD), and fibroproliferative DAD. A linear index was used to estimate the global severity of involvement by CT and histopathological analysis.

Results: There was a positive correlation between patient mean CT and histopathological severity score indexes - Pearson correlation coefficient (R) = 0.66 (p = 0.0078). When analyzing the mean lung involvement percentage of each finding, positive correlations were found between the normal lung percentage between postmortem CT and histopathology (R=0.65, p = 0.0082), as well as between ground-glass opacities in postmortem CT and normal lungs in histopathology (R=0.65, p = 0.0086), but negative correlations were observed between ground-glass opacities extension and exudative diffuse alveolar damage in histological slides (R=-0.68, p = 0.005). Additionally, it was found is a trend toward a decrease in the percentage of normal lung tissue on the histological slides as the percentage of consolidations in postmortem CT scans increased (R =-0.51, p = 0.055). The analysis of the other correlations between the percentage of each finding did not show any significant correlation or correlation trends (p ≥ 0.10).

Conclusions: A minimally invasive autopsy is valid. As the severity of involvement is increased in CT, more advanced disease is seen on histopathology. However, we cannot state that one specific radiological category represents a specific pathological correspondent. Ground-glass opacities, in the postmortem stage, must be interpreted with caution, as expiratory lungs may overestimate disease.

Keywords: Autopsy; Pathology; Thorax; Tomography.

Fig. 1

3D volume rendering reformat from a postmortem chest CT from our study (using RadiAnt™ DICOM Viewer 2022.1 Software – 3D Preset: Bones and Skin 3) shows how the postmortem expired lungs (in blue) have their anterior lower limits around the 4th or 5th intercostal spaces. From this reconstruction, it is possible to understand why the 2nd anterior intercostal space was used for the tissue sample collection of the upper regions and the 3rd anterior intercostal space was used for the tissue sample collection of the inferior regions. The limit between the lateral and medial regions was the midclavicular line. The 4 regions of access to tissue sample collection are also shown: SL = superolateral; SM = superomedial; IL = inferolateral; IM = inferomedial.

Fig. 2

Examples of postmortem CT findings of our sample: A) Normal lung parenchyma (white ellipse). B) Ground-glass opacities (white asterisk). C) Crazy paving (black ellipse). D) Small consolidations (black arrows). E) Large consolidations (black arrowheads).

Fig. 3

Examples of postmortem histological findings of our sample: A) Normal lung parenchyma. B) Acute/Exudative Diffuse Alveolar Damage. C) Fibroproliferative diffuse alveolar damage.

Fig. 4

Flow diagram showing the initial number of patients and patients excluded. Afterward, from the patients not excluded, some regions had to be excluded because of insufficient and/or inappropriate material. In the end, 96 lung regions were analyzed.

Fig. 5

: The correlation between CT and Histopathological severity score indexes.

Fig. 6

: Correlation - Mean lung involvement percentage in the blades and in the CT for each finding.

Fig. 7

A) Postmortem Chest CT Image, Axial View, Left Upper Regions. There is a large area of normal lung parenchyma (ellipse). B) Histopathological sample of the same regions: Photomicrograph showing normal lung with open airspaces, thin alveolar septa, no inflammation and mild capillary congestion, commonly seen in autopsy specimens - HE Staining. Scale Bar - 200 µm - Objective 10x.

Fig. 8

A) Postmortem Chest CT Image, Axial View, Right Upper Regions: There is a considerable amount of ground-glass opacities. B) Histopathological sample of the same regions: Photomicrograph of Acute Exudative DAD showing moderate septal inflammation, intense vascular congestion (ellipse), intra-alveolar fibrin deposition (asterisk) and formation of hyaline membranes (arrows) - HE Staining. Scale Bar - 200 µm - Objective 10x.

Fig. 9

A) Postmortem Chest CT Image, Axial View, Right Upper Regions: There is a considerable amount of ‘crazy paving’ (thickened interlobular septa and intralobular lines superimposed on a background of ground-glass opacities). B) Histopathological sample of the same regions: Photomicrograph showing mixed DAD with some characteristics of acute DAD such as hyaline membranes (arrows) and abundant inflammatory cells (ellipse), as well as of fibroproliferative DAD with collagen deposition forming intra-alveolar plugs and septal thickening (asterisk) - HE Staining. Scale Bar - 200 µm - Objective 10x.

Fig. 10

A) Postmortem Chest CT Image, Axial View, Right Upper Regions: There is a considerable amount of lung consolidations – small and large. B) Histopathological sample of the same regions: Photomicrograph of intense fibroproliferative DAD showing collagen deposition forming intra-alveolar plugs throughout the slide (asterisk) - HE Staining. Scale Bar - 200 µm - Objective 10x.