Clinical, Virological, and Histopathological Manifestations of Fatal Human Infections by Avian Influenza A(H7N9) Virus

Abstract

BACKGROUND: Systematic analysis of histopathological and serial virological changes of fatal influenza A(H7N9) cases is lacking. METHODS: Patients with A(H7N9) infection admitted to our intensive care unit during 10-23 April 2013 were included. Viral loads in the respiratory tract, as inferred from the cycle threshold (Ct) value of reverse transcription polymerase chain reaction (RT-PCR), and the serum hemagglutination inhibition (HAI) antibody titer, were analyzed. Postmortem biopsies of the lung, liver, kidney, spleen, bone marrow, and heart were examined. RESULTS: Twelve patients (6 deaths, 6 survivors) were included. Median viral load was higher in sputa than the nasopharyngeal swabs for fatal cases (median Ct, 23 vs 30.5; P = .08). RT-PCR for A(H7N9) was positive in stool samples (4/6 [67%]) of fatal 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% vs 50%). HAI titers increased by >/=4-fold in those with convalescent sera. Postmortem biopsy for 3 patients showed acute diffuse alveolar damage. Patient 1, who died 8 days after symptom onset, had intra-alveolar hemorrhage. Patients 2 and 3, who died 11 days after symptom onset, had pulmonary fibroproliferative changes. 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 are compatible with impaired renal or liver function. CONCLUSIONS: Fatal A(H7N9) infection was characterized by viral and secondary bacterial pneumonia with 67% having positive RT-PCR in stool.