OBJECTIVETo identify histopathologic changes of major organs and to correlate clinical symptoms in patients infected by avian influenza H5N1.

METHODSAutopsy study was performed in two patients died of avian influenza HSN1 infection, following conventional protocols and strict safety procedures. Tissue samples from all major organs of two cases and lung samples of one case were collected and fixed in 4% formaldehyde. Histopathologic changes were evaluated by light microscope.

RESULTSDiffuse alveolar damage (DAD) of the lung was seen in both cases. Lesions at various stages of development were seen involving different areas of the lung. At the early stages, the lungs exhibited exudative changes, including capillary congestion, necrosis of alveolar epithelial cells, and intra-alveolar edema. Hyaline membranes were prominent and diffusely distributed along alveoli. In the middle-late stages of the disease, the lungs exhibited proliferative and fibrotic changes, including proliferation of pneumocytes and bronchial epithelium, fibrosis of the interstitium and alveolar spaces. Lung biopsy tissue of one case showed DAD and interstitial fibrosis in a background of bronchiectasis. Lymph nodes and spleens showed quantity reduction of lymphocytes and active hemophagocytosis. Other changes in major organs included interstitial carditis in one case and acute renal tubular necrosis in one case. In one case, the brain showed edema with cytoplasmic eosinophilia, loss of structure, axon welling and focal necrosis around ventricle. Multiple foci of trophoblastic necrosis with dystrophic calcification were observed in placenta of one pregnant patient. Acute necrotizing deciduitis was found focally. Sections of fetal lung showed edema and scattered interstitial neutrophils were consistent with acute interstitial pneumonitis.

CONCLUSIONSThe respiratory tract is the major target of avian influenza A H5N1 virus infection. The changes of DAD in the lungs resulted in hypoxia, leading to multiple organ failure and death.

Adult ; Alveolar Epithelial Cells ; pathology ; Animals ; Birds ; Fatal Outcome ; Female ; Humans ; Influenza A Virus, H5N1 Subtype ; pathogenicity ; Influenza in Birds ; pathology ; physiopathology ; virology ; Influenza, Human ; pathology ; Male ; Pregnancy ; Pulmonary Fibrosis ; etiology ; pathology

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
Adenosine Monophosphate/therapeutic use* ; Alanine/therapeutic use* ; Alveolar Epithelial Cells/virology* ; Antibodies, Neutralizing/therapeutic use* ; COVID-19/virology* ; Down-Regulation ; Drug Discovery ; Human Embryonic Stem Cells/metabolism* ; Humans ; Immunity ; Lipid Metabolism ; Lung/virology* ; RNA, Viral/metabolism* ; SARS-CoV-2/physiology* ; Virus Replication/drug effects*

OBJECTIVETo study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection.

METHODSEight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out.

RESULTSThe major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%).

CONCLUSIONNecrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.

Adolescent ; Adult ; Aged ; Alveolar Epithelial Cells ; pathology ; Antigens, Viral ; metabolism ; Apoptosis ; Autopsy ; Biopsy, Needle ; Bronchiolitis, Viral ; pathology ; Child ; Child, Preschool ; Female ; Hemagglutinin Glycoproteins, Influenza Virus ; metabolism ; Humans ; Influenza A Virus, H1N1 Subtype ; immunology ; Influenza, Human ; metabolism ; mortality ; pathology ; virology ; Lung ; immunology ; metabolism ; pathology ; Male ; Middle Aged ; Nuclear Proteins ; metabolism ; Pulmonary Alveoli ; pathology ; Pulmonary Fibrosis ; pathology ; Young Adult