Search

Background The high case fatality rate of influenza A(H7N9)-infected patients has been a major clinical concern. Methods To identify the common causes of death due to H7N9 as well as identify risk factors associated with the high inpatient mortality, we retrospectively collected clinical treatment information from 350 hospitalized human cases of H7N9 virus in mainland China during 2013–2017, of which 109 (31.1%) had died, and systematically analyzed the patients' clinical characteristics and risk factors for death. Results The median age at time of infection was 57 years, whereas the median age at time of death was 61 years, significantly older than those who survived. In contrast to previous studies, we found nosocomial infections comprising Acinetobacter baumannii and Klebsiella most commonly associated with secondary bacterial infections, which was likely due to the high utilization of supportive therapies, including mechanical ventilation (52.6%), extracorporeal membrane oxygenation (14%), continuous renal replacement therapy (19.1%), and artificial liver therapy (9.7%). Age, time from illness onset to antiviral therapy initiation, and secondary bacterial infection were independent risk factors for death. Age >65 years, secondary bacterial infections, and initiation of neuraminidase-inhibitor therapy after 5 days from symptom onset were associated with increased risk of death. Conclusions Death among H7N9 virus–infected patients occurred rapidly after hospital admission, especially among older patients, followed by severe hypoxemia and multisystem organ failure. Our results show that early neuraminidase-inhibitor therapy and reduction of secondary bacterial infections can help reduce mortality. Characterization of 350 hospitalized avian influenza A(H7N9)-infected patients in China shows that age >65 years, secondary bacterial infections, and initiation of neuraminidase-inhibitor therapy after 5 days from symptom onset were associated with increased risk of death. [ABSTRACT FROM AUTHOR]

Avian influenza A ( H7N9) is a severe disease with high mortality. Hypercytokinemia is thought to play an important role in the pathogenesis. This study was to investigate the efficiency of plasma exchange ( PE) + continuous veno-venous hemofiltration ( CVVH) on the removal of inflammatory mediators and their benefits in the management of fluid overload and metabolic disturbance. In total, 40 H7N9-infected patients were admitted to our hospital. Sixteen critically ill H7N9-infected patients received combination of PE and CVVH. Data from these 16 patients were collected and analyzed. The effects of PE + CVVH on plasma cytokine/chemokine levels and clinical outcomes were examined. H7N9-infected patients had increased plasma levels compared to healthy controls. After 3 h of PE + CVVH treatment, the cytokine/chemokine levels descended remarkably to lower levels and were maintained thereafter. PE + CVVH also benefited the management of fluid, cardiovascular dysfunction and metabolic disturbance. Of the 16 critically ill patients who received PE + CVVH, 10 patients survived. PE + CVVH decreased the plasma cytokine/chemokine levels significantly. PE + CVVH were also beneficial to the management of severe avian influenza A ( H7N9). [ABSTRACT FROM AUTHOR]

Summary Objectives To investigate peripheral blood lymphocyte subgroups response to the H7N9 virus and identify potential correlations between the anti-viral response and clinical outcomes in infected patients. Methods T lymphocyte subgroups, cytokine/chemokine levels in peripheral blood and H7N9 viral loads in the sputum were measured for 53 H7N9 patients (14 lethal and 39 non-lethal cases). 22 H1N1 patients and 15 healthy volunteers were selected as controls. Results Low proportions of T cells were observed in H7N9-infected individuals, particularly those who later died, and these correlated with clinical APACHE II scores and H7N9 virus loads in sputum. T-cell levels fluctuated during hospitalization and decreased suddenly on the day of death in those who succumbed to infection, whereas a dramatic increase in lymphocyte subgroups was observed in those who survived beyond the early stage of infection, with the levels of most lymphocyte subgroups significantly higher during the recovery phase compared to the early phase of infection. A cytokine/chemokine storm was also confirmed in this study. Conclusions H7N9-infected individuals have low proportions of peripheral blood T lymphocyte subgroups, particularly those suffering fatal infections. The numbers of CD3 + T cells (including CD4 + and CD8 + T cells) may predict the clinical outcome of human H7N9 infection. [ABSTRACT FROM AUTHOR]

Serological surveillance conducted in areas of an outbreak of influenza A(H7N9) infection in China found no seropositivity for antibodies specific for avian-origin influenza A(H7N9) among 1129 individuals of the general population, whereas >6% of 396 poultry workers were positive (on the basis of a hemagglutination inhibition titer of ≥ 80) for this subtype, confirming that infected poultry is the principal source of human infections and that subclinical infections are possible. Fourteen days after symptom onset, elevated levels of antibodies to A(H7N9) were found in 65.8% of patients (25/38) who survived but in only 28.6% of those (2/7) who died, suggesting that the presence of antibodies may improve clinical outcome in infected patients. [ABSTRACT FROM AUTHOR]

The avian-origin influenza A(H7N9) virus has emerged as a cause of human infections. The authors describe the clinical, virological, and histopathological changes of 6 fatal human infections by avian influenza A(H7N9) virus.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. [ABSTRACT FROM AUTHOR]

• In the past 6 years, the prevalence of PB2-V292I mutation in H7N9 viruses isolated from humans and birds has increased • The phylogenetic tree showed that influenza A/H7N9 has a lineage based on the strains containing PB2-292I. • Influenza H7N9 virus carrying PB2-292I/627 K exhibit increased replication in mammalian cells. Characterization of host adaptation markers among human isolates is important for recognizing the potential for cross-species transmission in avian influenza A viruses. Here, we studied two new potential adaptive mutations, V292I and D740A, in the PB2 protein that were identified by a multi-factor regression model. The study shows that the prevalence of the PB2-V292I mutation is increased in H7N9 influenza viruses isolated from both humans and birds over the past 6 years. The phylogenetic tree showed that influenza A/H7N9 has a lineage based on the strains containing PB2-292I. Polymerase complexes containing PB2-292I/627K derived from H7N9 exhibit increased polymerase activity. PB2-292I coupled with 627K also enhances viral transcription and replication in cells, whereas PB2-292I alone did not show the same effect in the H7N9 virus. However, PB2-740A only had a limited prevalence in 2013, and the change from D to A in PB2-740A may have a negative effect on the replication of the H7N9 virus in cells. [ABSTRACT FROM AUTHOR]