Clinical,Virological,and Histopathological Manifestations Of Fatal Humal Infections By Avian Influenza A(H7N9)Virus

Part1Cliniacl and Viral Manifestations of Severe Human Infections by Avian Influenza A(H7N9) VirusBackgroundThe avian influenza A(H7N9) virus [A(H7N9)] human infections appeared in Eastern China starting in February2013. A total of133human A(H7N9) virus infection with a case-fatality rate of32%were reported within3months after the announcement of the first case on31March2013. Systematic analysis of clinical and serial virological changes of severe influenza A(H7N9) cases is lacking.MethodPatients with A(H7N9) infection admitted to our intensive care unit during10-23April2013were included. Viral loads in the respiratory tract, and other samples, as inferred from the cycle threshold (Ct) value of reverse transcription polymerase chain reaction (RT-PCR), and the serum hemagglutination inhibition (HAI) antibody titer, cytokines and chemokines on admission and the worst clinical day were analyzed.ResultTwelve patients (6deaths,6survivors) were included. Median viral load was higher in sputa than the nasopharyngeal swabs for fetal cases (median Ct,23vs30.5; P =0.08). RT-PCR for A(H7N9) was positive in stool samples (4/6[67%]) of fetal cases and (2/6[33%]) of survivors, but was negative in the cerebrospinal fluid, urine, or blood of all patients. Nosocomial bacterial infections were more common in patients who died than in survivors (83%vs50%). HAI titers increased by≥4-fold in those with convalescent sera. Variation tendency of cytokines and chemokines were significantly different in patients who died than in survivors.ConclusionH7N9virus was tended to infect lower respiratory tract, Fatal A(H7N9) infection was characterized by deferred HAI titers, and67%having positive RT-PCR in stool. Part2Histopathological Manifestations of Fatal Human Infections by Avian Influenza A(H7N9) VirusBackgroundThere were375confirmed human infection with the H7N9avian influenza virus with a mortality over20%since the onset of the infection from February2013in China. Postmortem Finding of the patients with this novel avain influenza infection is lackingMethod6fetal cases with laboratory confirmed H7N9infection since March1,2013were included. Clinical data were retrospectively analyzed. Postmortem biopsies were examined in4patiets with informed consents. Detailed light microscopy of major organs was performed, including heart, lung, liver, spleen, kidney, brain and bone marrow. The lung tissue was further investigated by histochemistry, immunohistochestry and electron microscopy.ResultPostmortem biopsy for4patients showed acute diffuse alveolar damage. Patient1, who died8days after symptom onset, had intra-alveolar hemorrhage. Patients2and3, who died11days after symptom onset, had pulmonary fibroproliferative changes. Patient4, who died45days after symptom onset, had intraalveolar fibrin deposit and focal lymphocytic myocarditis and epicarditis. Reactive hemophagocytosis in the bone marrow and lymphoid atrophy in splenic tissues were compatible with laboratory findings of leukopenia, lymphopenia, and thrombocytopenia. Hypoxic and fatty changes of kidney and liver tissues were compatible with impaired renal or liver function. ConclusionThe pathology of patients with influenza A(H7N9) infection is similar with H5N1and compatible with pulmonary ARDS.