The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery to prolonged hospitalization. Using a multicolour assay for monitoring adaptive and innate immunity, here we dissect the kinetic emergence of different effector mechanisms across the spectrum of H7N9 disease and recovery. We find that a diversity of response mechanisms contribute to resolution and survival. Patients discharged within 2–3 weeks have early prominent H7N9-specific CD8+ T-cell responses, while individuals with prolonged hospital stays have late recruitment of CD8+/CD4+ T cells and antibodies simultaneously (recovery by week 4), augmented even later by prominent NK cell responses (recovery >30 days). In contrast, those who succumbed have minimal influenza-specific immunity and little evidence of T-cell activation. Our study illustrates the importance of robust CD8+ T-cell memory for protection against severe influenza disease caused by newly emerging influenza A viruses.

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Recent research has shown that social anxiety disorder (SAD) is accompanied by abnormalities in brain functional connections. However, these findings are based on group comparisons, and, therefore, little is known about whether functional connections could be used in the diagnosis of an individual patient with SAD. Here, we explored the potential of the functional connectivity to be used for SAD diagnosis. Twenty patients with SAD and 20 healthy controls were scanned using resting-state functional magnetic resonance imaging. The whole brain was divided into 116 regions based on automated anatomical labeling atlas. The functional connectivity between each pair of regions was computed using Pearson's correlation coefficient and used as classification feature. Multivariate pattern analysis was then used to classify patients from healthy controls. The pattern classifier was designed using linear support vector machine. Experimental results showed a correct classification rate of 82.5 % (p < 0.001) with sensitivity of 85.0 % and specificity of 80.0 %, using a leave-one-out cross-validation method. It was found that the consensus connections used to distinguish SAD were largely located within or across the default mode network, visual network, sensory-motor network, affective network, and cerebellar regions. Specifically, the right orbitofrontal region exhibited the highest weight in classification. The current study demonstrated that functional connectivity had good diagnostic potential for SAD, thus providing evidence for the possible use of whole brain functional connectivity as a complementary tool in clinical diagnosis. In addition, this study confirmed previous work and described novel pathophysiological mechanisms of SAD.

Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8+ T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38+HLA-DR+PD-1+ CD8+ T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38+HLA-DR+CD8+ T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients. Delayed clonal expansion associated with an early dichotomy at a transcriptome level (as detected by single-cell RNAseq) is found in CD38+HLA-DR+CD8+ T cells from patients who succumbed to the disease, suggesting a divergent differentiation pathway of CD38+HLA-DR+CD8+ T cells from the outset during fatal disease. Our study proposes that effective expansion of cross-reactive influenza-specific TCRαβ clonotypes with appropriate transcriptome signatures is needed for early protection against severe influenza disease.