Postmortem Findings in Italian Patients With COVID-19: A Descriptive Full Autopsy Study of Cases With and Without Comorbidities

Abstract

Background: Descriptions of the pathological features of coronavirus disease-2019 (COVID-19) caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emanate from tissue biopsies, case reports, and small postmortem studies restricted to the lung and specific organs. Whole-body autopsy studies of COVID-19 patients have been sparse.

Methods: To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Tissues from the lung, heart, liver, kidney, spleen, and bone marrow (but not the brain) were examined. Only lung tissues were subject to transmission electron microscopy.

Results: COVID-19 caused multisystem pathology. Pulmonary and cardiovascular involvement were dominant pathological features. Extrapulmonary manifestations included hepatic, kidney, splenic, and bone marrow involvement, and microvascular injury and thrombosis were also detected. These findings were similar in patients with or without preexisting medical comorbidities.

Conclusions: SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without comorbidities.

Keywords: COVID-19; SARS-CoV-2; autopsy; comorbidities; pathology.

Figure 1.

Pathological findings in lung. A1, Lungs showed an increase in volume and were firmer and heavier than normal. A2 and A3, Light microscopic analysis shows parenchymal multifocal damage with intraalveolar inflammation, fibrin, and hyaline membranes consistent with a diagnosis of diffuse alveolar damage. Both acute exudative inflammatory process and fibrous proliferative phase were found. A3 and A4, Hyperplasia of type II pneumocyte, characterized by amphophilic cytoplasm, large nuclei, and prominent nucleoli, are shown (arrows). B1, Alveolar duct fibrosis. B2, Fibrin thrombi in capillaries. B3, Vascular injury including vessel vasculitis and vascular edema. B4, Pleural fibrosis. Abbreviation: H&E, haematoxylin and eosin. Scale bars: A2, 14 µm; A3–B3, 7 µm; B4, 21 µm.

Figure 2.

Immunohistological characterization of lung tissue. A1–A4, CD26/dipeptidyl peptidase-4 expression in lung tissue. Numerous strongly positive CD26⁺ cells are seen in the alveolar septa. A3, Intense staining is seen in the type II pneumocytes (arrows). A4, Positive cells are also seen entrapped with fibrin in the vascular lumen. B1–B4, CXCR3/CD183 immunostaining shows intense staining of lymphocytes localized in the inflammatory perivascular aggregates and spread into alveolar septa and alveolar spaces. Scale bars: A1 and B1, 100 µm; A2, A3, and B4, 7 µm; A4, B2, and B3, 14 µm.

Figure 3.

SARS-CoV-2 detection in lung tissue by transmission electron microscopy. A, SARS-CoV-2 particles are visible in virus-containing compartments in type II pneumocytes (arrows). B–D, Numerous viral particles are enclosed in single-membrane vacuoles (arrow). Other, very small vesicles contain single viral particles (arrowheads). Scale bars: A, 1 µm; B–D, 200nm.

Figure 4.

Histological changes in heart. A1, Hearts were increased in size and weight. The myocardium appeared pale and flabby. Endocardium showed punctuate petechial hemorrhages. A2, Age-related disease of the heart was represented by volume changes of the left ventricular cavity and exacerbated by systemic hypertension with valve changes including calcification of the mitral annulus and aortic valve. A3 and A4, Heart tissue shows myocytes hypertrophy, and variable degrees of interstitial and vascular fibrosis with mononuclear cells infiltrating adventitia. B1, Active myocarditis was characterized by mononuclear, predominantly lymphocytic infiltrate, associated with focal myocytes necrosis (B2). B3, Fibrinous, hemorrhagic areas with myofibers disarray were present. B4, Pericarditis with lymphocytic infiltration and increase in fibrous tissue was seen in all patients. Abbreviation: H&E, haematoxylin and eosin. Scale bars: A3 and B4, 21 µm; A4–B2,7 µm; B3, 14 µm.

Figure 5.

Pathological findings in liver and kidney. A1, Liver tissue shows sinusoidal congestion and extravasation of red blood cells into the space of Disse. In some cases, small vein congestion (A2) and hepatic necrosis (A3) were reported. A4, Inflammatory infiltration was observed. A1, A2, and A4, Macrovacuolar and microvacuolar steatosis were observed in the majority of cases. B1, Kidney glomerular endothelial cells were swollen. B2, Fibrin deposit is visible underneath the Bowman capsule. B3, Tubulointerstitial inflammation and (B4) glomerular sclerosis were observed. Abbreviation: H&E, haematoxylin and eosin. Scale bars: A1–A4, and B3, 50 µm; B1, B2, and B4, 14 µm

Figure 6.

Histology of spleen and bone marrow. A1 and A2, Lymphoid hypoplasia is visible in the splenic white pulp. B1 and B2, Bone marrows tissue shows replacement of red hematopoietic bone marrow with yellow adipocyte-rich marrow. Megakaryocyte hyperplasia is observed (arrows). Abbreviation: H&E, haematoxylin and eosin. C1, Macrophages (CD68⁺) are present in bone marrow tissue. C2, CD68⁺ cells displaying features of hemophagocytosis (arrow). Scale bars: A1, A2, B2–C2, 7 µm; B1, 100 µm.