Respiratory Viruses

 Cumulative incidence curves for progression to lower respiratory tract disease following human rhinovirus infection in all subjects, stratified into 4 mutually exclusive levels of risk by score
Cumulative incidence curves for progression to lower respiratory tract disease following human rhinovirus infection in hematopoeitic cell transplant recipients, stratified into 4 mutually exclusive levels of risk by score. Waghmare et al. Human Rhinovirus Infections in Hematopoietic Cell Transplant Recipients: Risk Score for Progression to Lower Respiratory Tract Infection.Biol Blood Marrow Transplant. 2019 May; 25(5): 1011–1021.

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 and viral risk factors associated with disease progression, prolonged viral shedding, and clinical outcomes.

A specific area of focus is the identification of clinical factors associated with progression from upper to lower respiratory tract infection; we recently developed a weighted risk score for progression of human rhinovirus (HRV) from upper to lower respiratory tract infection and identified risk factors significantly associated with progression. We also found high discordance rates between upper and lower respiratory tract infection for HRV, human metapneumovirus, parainfluenza virus-3, and adenovirus. In a separate analysis to characterize risk factors for prolonged viral shedding in HCT recipients with HRV infection, we demonstrated that initial high viral load is associated with prolonged shedding. We are also 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 infection of the upper respiratory tract that were predictive of progression to lower respiratory tract infection. In complimentary efforts, we are optimizing and validating simple self-collection sampling methods for respiratory viruses that can be used by patients at home. We are also interested in determining the clinical significance of specific respiratory viruses in immunocompromised patients. An additional area of focus is evaluating new antivirals for respiratory viral infections in HCT recipients.