The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities

Abstract

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m²). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.

Keywords: Autopsy; COVID-19; Coagulopathy; Diffuse alveolar damage; Heart; Kidney; Liver; SARS-CoV-2; Spleen; Viral pneumonia.

Fig. 1

Houston Case One (HC1). (A) Pulmonary alveoli exhibit congested capillaries, hyaline membranes and increased numbers of mononuclear cells in the alveolar spaces. (B) Hyaline membranes resulting from capillary leak leading to fibrinous exudate and fibrin precipitate. (C) Collection of pneumocytes showing squamous metaplasia. (D) Alveoli exhibiting congested alveolar capillaries containing leukocytes (2 arrows) and a megakaryocyte with large hyperchromatic nucleus (single arrow) and alveolar spaces containing foamy macrophages of variable size. (A, B, C, D; Hematoxylin and eosin stains). (Magnification bar: A 200 µm; B, C, and D 20 µm).

Fig. 2

Houston Case One (HC1). Immunohistochemical findings for lung pathology. Alveoli contain a mildly increased number of CD3+ T lymphocytes (A), a moderately increased number of CD68+ macrophages (B) and increased numbers of TTF+ pneumocytes (C). Clusters of pneumocytes exhibit squamous metaplasia as indicated by positive CK 5/6 expression (D). (Magnification bar: A, B, C and D; 100 µm).

Fig. 3

Houston Case One (HC1). Electron micrographs. (A) Alveolar capillaries contain erythrocytes and neutrophils identified by the presence of characteristic granules (red star). (B) Higher magnification view of cellular 500 nanometer particles which likely represent swollen lysosomes (azurophil granules).

Fig. 4

Houston Case One (HC1). Electron micrographs. (A) Alveolar capillaries contain erythrocytes and strands of electron dense fibrin (arrows). The edematous alveolar septum also has larger precipitates of fibrin outside of the capillary (stars). The alveolar lining cells have been lost. (B) Higher magnification view of fibrin deposit within an alveolar capillary (star).

Fig. 5

Houston Case One (HC1). Electron micrographs. (A) Large electron-dense, intra-alveolar fibrin deposits are in close apposition to the alveolar septum (arrow). (B) Higher magnification view of intra-alveolar fibrin deposit intermixed with collagen fibrils.

Fig. 6

Houston Case One (HC1). (A) Epicardium exhibits a focus with lymphocytic infiltrate indicative of lymphocytic pericarditis. (B) Myocardium is edematous as manifest as separation of the cardiomyocytes (CMC) and capillaries. The CMC in the center shows vacuolar degenerative change (star). No inflammatory cells are present. (C) Liver shows moderate macro-steatosis and altered, shrunken hepatocytes likely representing incipient apoptosis. (D) Renal glomerulus with focally congested capillaries. (A, C and D, Hematoxylin and eosin stains; B, 1-micron section, toluidine blue stain). (Magnification bar: A and C, 100 µm; B and D, 20 µm).

Fig. 7

Houston Case One (HC1). Spleen. (A) Expansion of red pulp and shrinking of white pulp with absent marginal zones. (B) Red pulp with lymphoplasmacytic infiltrate. (C) White pulp with scattered immunoblasts. (D) Red pulp with lymphoplasmacytic infiltrate. (Hematoxylin and eosin stains).

Fig. 8

Houston Case Two (HC2). (A and B) Axial CT images which demonstrate bilateral upper and lower lobe ground-glass and early consolidative alveolar opacities some of rounded morphology, classically described with COVID-19.

Fig. 9

Houston Case Two (HC2). (A) Pulmonary thromboembolus obstructing segmental pulmonary artery; one of several in both lungs. (B) Terminal bronchiole with interstitial lymphocytic infiltrates. (C) Interstitial and intra-alveolar infiltrates composed predominantly of lymphocytes. (D) Intra-alveolar fibrin deposit (star). The pulmonary arteriole has a thickened wall indicative of chronic pulmonary hypertension. (A, B, C, D; Hematoxylin and eosin stains). (Magnification bar: A, 500 µm; B, 100 µm; C and D, 50 µm).

Fig. 10

Houston Case Two (HC2). (A and B) Myocardium is edematous and small blood vessels are congested. The CMC exhibit multifocal vacuolar degenerative changes. No inflammatory cellular infiltrates are present. Note the increased width of these CMC compared to those of HCO (Fig. 6B). The patient's heart weighed 1070 g. (C) The epicardium exhibits a lymphocytic infiltrate adjacent to a vein. (D) Testis with thrombi in peritesticular veins. (A and B, one-micron sections, toluidine blue stain; C and D, hematoxylin and eosin stains). (Magnification bar: A and B, 20 µm; C, 100 µm; D 500 µm).

Fig. 11

Houston Case Three (HC3). (A) Pulmonary parenchyma showing interstitial pneumonia with DAD pattern. (B) Bronchiole with fibrinous exudate. (C) Alveolar capillaries contain numerous megakaryocytes with large hyperchromatic nuclei. (D) Alveoli contain enlarged reactive pneumocytes and fibrin deposit. (A, B, C, and D; Hematoxylin and eosin stains). (Magnification bar: A, 200 µm; B, 100 µm; C and D, 20 µm).

Fig. 12

(A) Immunohistochemistry for CD61 (Glycoprotein IIIa) shows numerous megakaryocytes and platelets (small punctate bodies) in alveolar capillaries. From Houston Case Two (HC2). (Magnification bar, 20 µm). (B) Electron micrograph shows a collection of viral particles in a vacuole inside a renal glomerular endothelial cell from Houston Case One (HC1). X50,000. (C) Electron micrograph of a single 100 nanometer viral particle free in the cytoplasm of a renal glomerular endothelial cell from HC1. Note the nucleocapsid and membrane spike proteins. X50,000.