The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation

Abstract

The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy.

Keywords: Autopsy; COVID-19; Capillaritis; Lung; Microthrombosis.

Fig. 1

Laboratory data patient 3

Fig. 2

Patient 1. a Significant increase of IL-1beta and IL-6 mRNA in lung tissue of patient 1 as compared with patients 2 and 3. b Neutrophilic septal capillaritis (arrowheads) with associated intra-alveolar edema. H&E (× 200). The insert shows nuclear dust in higher magnification. c Neutrophilic capillaritis associated with microthrombosis (arrowheads) and intra-alveolar hemorrhage. H&E (× 200). The insert shows endothelial necrosis with nuclear dust (arrow) and transmigration of neutrophils (× 400). d NASD chloroacetate esterase histochemistry highlights intra- und perivascular accumulation of neutrophils (granulocytes appear red) (× 200)

Fig. 3

Patient 2. a Gross image of cut surface of the lower pulmonary lobe with multiple thrombi in small vessels, focally accompanied by perifocal hemorrhage (arrows) and consolidation and discoloration of the parenchyma. b The lower lobes show advanced diffuse alveolar damage with fibrinous exudate (black arrowheads), hyaline membranes (blue arrowheads), incipient hyperplasia of alveolar epithelium, and increased desquamation of macrophages. H&E (× 200). c Thrombosis of two medium-sized pulmonary blood vessels with marked endotheliitis (black arrowheads), fibrinoid necrosis of the vessel wall (blue arrowheads), and thrombi in engorged surrounding capillaries. H&E (× 200). d Massive hyperplasia of type 2 pneumocytes surrounding the fibrinous exudate with macrophages. Pan-cytokeratin (AE1/3) immunohistochemical stain (× 200)

Fig. 4

Patients 3 and 4. Patient 3. a Lower lobe with diffuse alveolar damage with multinuclear alveolar macrophages (arrows) and striking leukostasis (insert), both H&E (× 200). b Virus particles (red arrowhead) are often found in endothelial cells (white arrowhead, erythrocyte; gray arrowhead, nucleus of endothelial cell); insert bottom, bar scale 100 nm. The majority of viruses are located in membrane-bound compartments, likely representing endosomes, insert top (bar scale 200 nm). Patient 4. c The lung shows features of prolonged ARDS with extensive epithelial hyperplasia and focal squamous metaplasia. H&E (× 100). d Typical changes of organizing pneumonia with plugs of loose connective tissue with concentrically arranged fibroblasts and central accumulation of inflammatory cells filling alveolar spaces. H&E (× 100)