A well-known source of misery for immunocompetent people, respiratory viruses are a major cause of morbidity and mortality in immunocompromised patients. Our group seeks to improve prevention, diagnosis and treatment strategies for respiratory virus infections (e.g., respiratory syncytial virus, parainfluenza viruses, influenza A and B, adenovirus, human metapneumovirus, rhinoviruses, coronaviruses (including SARS-CoV-2), and enteroviruses) after hematopoietic cell transplant (HCT). We are interested in clinical, host defense, and viral risk factors associated with disease progression, prolonged viral shedding, and clinical outcomes.
Areas of interest in our clinical research are (i) the identification of clinical factors associated with progression from upper to lower respiratory tract infection, (ii) the impact of pre-transplant respiratory virus infections on outcomes after transplantation, (iii) the importance of sampling techniques from different anatomical sites (including home testing from respiratory and blood compartments [Tasso devices]), (iv) the significance of viral load on shedding and outcomes, and (v) factors associated with prolonged viral shedding in HCT recipients.
We are also interested in the development and evaluation of new antiviral, immunotherapy and vaccine strategies for respiratory viral infections in immunocompromised persons.
In the laboratory, we are investigating biomarkers that may allow risk-stratification of patients for clinical trials and/or targeted disease management. Toward this goal, we recently applied RNAseq to identify host transcriptional signatures in blood collected at the time of human rhinovirus and parainfluenza virus infections of the upper respiratory tract that were predictive of progression to lower respiratory tract infection. Furthermore, we are testing multifunctional T cell immunity to respiratory viruses (e.g. parainfluenza virus 3) using multicolor flow cytometry to better understand the role of T cell immunity in the risk of progression. To characterize the humoral immune response to respiratory viruses, we are using phage immunoprecipitation sequencing (PhIP-Seq) in the form of VirScan, allowing efficient simultaneous assessment of viral epitope expansion kinetics over time of a large number of viruses, including all human respiratory viruses and herpesviruses. We also use MSD sandwich immunoassays to characterize virus-specific immune responses. Different Tasso Devices permit home-based collection for both serologic and cellular assays, including the analysis of transcriptional signatures.