Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)

Abstract

Background: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV).

Methods: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue.

Results: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients.

Conclusions: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.

Figure 1

Gross and histological features of lungs in patients with severe acute respiratory syndrome. (A) Extensive consolidation with a greyish cut surface was noted in most of the patients. (B) All the patients showed features of the acute phase of diffuse alveolar damage, with pulmonary oedema and formation of a hyaline membrane. The airspaces are indicated by asterisks and some of the hyaline membranes lining the alveolar spaces are highlighted by arrows (haematoxylin and eosin stain; original magnification, ×100). (C) Mild infiltrate of interstitial inflammatory cells with interstitial thickening, accompanied by dilated airspaces (the asterisk indicates the dilated airspace). A small amount of hyaline membrane, as indicated by the arrow, was still evident (haematoxylin and eosin stain; original magnification, ×100). (D) Pronounced interstitial fibrosis with honeycombing was noted in patient 7 (asterisks indicated the abnormally dilated airspaces; Masson’s trichrome stain; original magnification, ×40).

Figure 2

Bronchiolitis obliterans organising pneumonia (BOOP)-like lesion in patients with severe acute respiratory syndrome. (A) A BOOP-like lesion was evident with cellular organising plugs within the small airways and airspaces (asterisks indicate some of the lesions). Lesions were typically located in the subpleural region (the visceral pleural surface is indicated by arrows; haematoxylin and eosin stain; original magnification, ×40). (B) Higher power view of cellular organising plugs (asterisk). The main cellular component consisted of histiocytes, which were CD68 positive (data not shown) (haematoxylin and eosin stain; original magnification, ×200).

Figure 3

Atypical pneumocytes in patients with severe acute respiratory syndrome. (A) Multi-nucleated giant pneumocytes with irregularly distributed nuclei were evident (indicated by arrows; haematoxylin and eosin stain; original magnification, ×400). (B) A giant atypical pneumocyte with prominent eosinophilic nucleoli (indicated by arrow; haematoxylin and eosin stain; original magnification, ×400).

Figure 4

Ultrastructural features of viral particle containing lung cells. (A) Ultrastructural section from patient 3. Viral-like particles with sizes ranging from 60 to 90 nm were noted within dilated cytoplasmic vesicles. Some of the better preserved structures consistent with viral envelopes are indicated by the arrows. The overall appearance was different from that of multivesicular bodies, which can be seen in some normal cells. Vero cell culture was used for comparison (B and C). (B) Section of an infected Vero cell showing similar features to those seen in the pneumocytes. The viral particles are found within the endoplasmic reticulum (indicated by the asterisk) and on the surface of the cytoplasmic membrane (indicated by the arrows). (C) Typical morphology of coronavirus particles in the supernatant of a Vero cell culture (indicated by the arrows; negative staining with 2% phosphotungstic acid).