Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age 1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C) 3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population. The clinical manifestations of SARS-CoV-2 infection in children are distinct from adults. Children with COVID-19 rarely exhibit severe respiratory symptoms and often remain asymptomatic 2 , whereas adults experience respiratory symptoms of varying severity; older adults and those with comorbidities such as hypertension and diabetes have substantially higher risks of developing COVID-19-associated ARDS with high mortality 2,6. In children, a rare but severe clinical manifestation of SARS-CoV-2 infection designated MIS-C, exhibits similarities to Kawasaki disease in certain inflammatory features and cardiovascular involvement while generally lacking severe respiratory symptoms 3-5. The nature of the immune response to SARS-CoV-2 in children with different clinical manifestations ranging from asymptomatic to MIS-C relative to the more common respiratory manifestations of COVID-19 in adults is unclear. The generation of virus-specific antibodies that neutralize or block infectivity is the most consistent correlate of protective immunity for multiple infections and vaccines 7,8. Antibodies specific for the major SARS-CoV-2 antigens, including the S protein which binds the cellular receptor for viral entry and the N protein necessary for viral replication, have been detected in actively infected patients and in patients with mild disease who recovered 9-12. Anti-S antibodies, in particular, can exhibit potent neutralizing activity and are currently being pursued as a therapeutic option for infusion into patients during severe disease and for targeted generation in vaccines 13-15. Defining the nature of the antibody response to SARS-CoV-2 infection as a function of age and clinical syndrome can provide essential insights for improved screening and targeted protection for the global population that continues to suffer from this relentless pandemic. In this study, we inves...

Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to un-targeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.