Objectives

The rapid emergence, spread, and disease severity of avian influenza A (H7N9) in China has prompted concerns about a possible pandemic and regional spread in the coming months. The objective of this study was to predict the risk of future human infections with H7N9 in China and neighboring countries by assessing the association between H7N9 cases at sentinel hospitals and putative agricultural, climatic, and demographic risk factors.

Methods

This cross-sectional study used the locations of H7N9 cases and negative cases from China's influenza-like illness surveillance network. After identifying H7N9 risk factors with logistic regression, we used Geographic Information Systems (GIS) to construct predictive maps of H7N9 risk across Asia.

Results

Live bird market density was associated with human H7N9 infections reported in China from March-May 2013. Based on these cases, our model accurately predicted the virus' spread into Guangxi autonomous region in February 2014. Outside China, we find there is a high risk that the virus will spread to northern Vietnam, due to the import of poultry from China.

Conclusions

Our risk map can focus efforts to improve surveillance in poultry and humans, which may facilitate early identification and treatment of human cases.

The I222K, I222R, and I222T substitutions in neuraminidase (NA) have been found in clinically derived 2009 pandemic influenza A/H1N1 viruses with altered susceptibilities to NA inhibitors (NAIs). The effects of these substitutions, together with the most frequently observed resistance-related substitution, H274Y, on viral fitness and resistance mechanisms were further investigated in this study. Reduced sensitivities to oseltamivir were observed in all three mutants (I222K, I222R, and I222T). Furthermore, the I222K and I222T substitutions had a combinational effect of further increasing resistance in the presence of H274Y, which might result from a conformational restriction in the NA binding site. Of note, by using molecular dynamics simulations, R152, the neighbor of T222, was observed to translate to a position closer to T222, resulting in the narrowing of the binding pocket, which otherwise only subtends the residue substitution of H274Y. Moreover, significantly attenuated NA function and viral growth abilities were found in the I222K+H274Y double mutant, while the I222T+H274Y double mutant exhibited slightly delayed growth but had a peak viral titer similar to that of the wild-type virus in MDCK cells. The relative growth advantage of the I222T mutant versus the I222K mutant and the higher frequency of I222T emerging in N1 subtype influenza viruses raise concerns necessitating close monitoring of the dual substitutions I222T and H274Y.

Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial inter-individual variability and have been linked to vaccine efficacy. To elucidate the underlying mechanism behind this variability, we conducted a genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK Biobank participants who were previously uninfected by SARS-CoV-2 and had received either the first dose (n = 54,066) or the second dose (n = 46,232) of COVID-19 vaccines. Our analysis revealed significant genome-wide associations between the IgG antibody serostatus following the initial vaccine and human leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1∗13:02 allele (MAF = 4.0%, OR = 0.75, p = 2.34e-16) demonstrated the most statistically significant protective effect against IgG seronegativity. This protective effect was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at position 71 on HLA-DRβ1 (p = 1.88e-25), leading to a change in the electrostatic potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA alleles on IgG responses was cell type specific, and we observed a shared genetic predisposition between IgG status and susceptibility/severity of COVID-19. These results were replicated within independent cohorts where IgG serostatus was assayed by two different antibody serology tests. Our findings provide insights into the biological mechanism underlying individual variation in responses to COVID-19 vaccines and highlight the need to consider the influence of constitutive genetics when designing vaccination strategies for optimizing protection and control of infectious disease across diverse populations.

Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.