Pulmonary pathologic findings of fatal 2009 pandemic influenza A/H1N1 viral infections

Abstract

Context: In March 2009, a novel swine-origin influenza A/H1N1 virus was identified. After global spread, the World Health Organization in June declared the first influenza pandemic in 41 years.

Objective: To describe the clinicopathologic characteristics of 34 people who died following confirmed A/H1N1 infection with emphasis on the pulmonary pathology findings.

Design: We reviewed medical records, autopsy reports, microbiologic studies, and microscopic slides of 34 people who died between May 15 and July 9, 2009, and were investigated either by the New York City Office of Chief Medical Examiner (32 deaths) or through the consultation service of a coauthor (2 deaths).

Results: Most of the 34 decedents (62%) were between 25 and 49 years old (median, 41.5 years). Tracheitis, bronchiolitis, and diffuse alveolar damage were noted in most cases. Influenza viral antigen was observed most commonly in the epithelium of the tracheobronchial tree but also in alveolar epithelial cells and macrophages. Most cases were reverse transcription-polymerase chain reaction positive for influenza. Histologic and microbiologic autopsy evidence of bacterial pneumonia was detected in 55% of cases. Underlying medical conditions including cardiorespiratory diseases and immunosuppression were present in 91% of cases. Obesity (body mass index, >30) was noted in 72% of adult and adolescent cases.

Conclusions: The pulmonary pathologic findings in fatal disease caused by the novel pandemic influenza virus are similar to findings identified in past pandemics. Superimposed bacterial infections of the respiratory tract were common. Preexisting obesity, cardiorespiratory diseases, and other comorbidities also were prominent findings among the decedents.

Figure 1

Representative histopathologic changes associated with fatal pandemic influenza A/H1N1 infection. Photomicrographs of hematoxylineosin–stained tissue sections and immunohistochemically stained sections to detect influenza viral antigen are shown. A, Acute necrotizing tracheitis and inflammation of the submucosal tracheal mucus glands (case 2) (hematoxylin-eosin, original magnification ×400). B and C, Immunohistochemical stain for influenza in a section of trachea. Viral antigen is stained red-brown on a hematoxylin-stained background. Arrow shows influenza antigen–positive cells in the submucosal gland. Arrowhead shows influenza antigen–positive cells in the tracheal epithelium. Section stained with anti-influenza primary antibody in B and without the primary antibody in C demonstrating specific staining (case 15) (original magnifications ×100 [B and C]). D and E, Immunohistochemical staining for influenza in a section of trachea. Viral antigen is stained red-brown on a hematoxylin-stained background. Arrows show influenza antigen-positive cells in acinar cells of a submucosal gland (D) and in ductal mucus cells, including basal cells (E) (case 17) (original magnifications ×1000 [D and E]). F, Section of lung showing a massive infiltration of neutrophils in the airspaces of alveoli associated with bacterial bronchopneumonia (case 19) (hematoxylin-eosin, original magnification ×100). G, Brown and Hopps modified tissue Gram stain showing chains of bacteria (arrow) morphologically compatible with streptococci (case 19) (original magnification ×1000). H, Immunohistochemical staining for influenza in a section of bronchus. Viral antigen is stained red-brown on a hematoxylin-stained background. Arrow shows influenza antigen–positive cells in the bronchial epithelium. Section shows an acute necrotizing bronchitis with transmural infiltration of inflammatory cells (case 25) (original magnification ×100). I, Section of lung showing diffuse alveolar damage with hyaline membranes lining an alveolar duct and adjacent alveoli (arrow). The alveolar air spaces contain edema fluid, strands of fibrin, desquamated epithelial cells, and inflammatory cells (case 10) (hematoxylin-eosin, original magnification ×100). J, Immunohistochemical staining for influenza in a bronchiole. Viral antigen is stained red-brown on a hematoxylin-stained background. Influenza antigen–positive cells are seen in the bronchiolar epithelium, including ciliated cells (arrowhead), and in the nuclei of some basilar cells (arrow) (case 25) (original magnification ×400). K through M, Immunohistochemical staining for influenza in alveolar cells. Viral antigen is stained red-brown on a hematoxylin-stained background. Influenza antigen–positive cells (arrows) include lveolar macrophages (K; case 1) and alveolar epithelial cells, both type I (L; case 15) and type II (M; case 24). The cytoplasm of the alveolar macrophages shown in K also contains bacteria morphologically compatible with Streptococcus pneumoniae (arrowhead) (original magnifications ×1000 [K, L, and M]).

Figure 2

Chest computed tomography examinations. The lungs of all 4 patients show rounded patches of ground-glass peribronchial opacity (yellow arrows) in a peripheral distribution. In A (case 24), the opacities are discrete and multifocal, while in B (case 26) they are confluent in subpleural areas, and in C (case 21) the entire right lung displays confluent ground-glass attenuation. These changes may correspond to areas of diffuse alveolar damage seen on histopathologic examination (see text). In addition to patchy ground-glass opacities, D (case 1) shows areas of denser consolidation in the right upper lobe and the superior segment of the right lower lobe (blue arrows) that are consistent with the bacterial pneumonia diagnosed in this patient.