No one likes getting sick. Sore throats, runny noses, headaches, coughs – all common symptoms of a cold or flu – are objectively unpleasant. For most, these respiratory virus infections are no reason for alarm, as they usually resolve on their own within a week or two and cause no lasting harm. They are perhaps just a good excuse to take it easy and spend a few days curled up under a blanket drinking hot tea and watching movies. For people who recently received an allogeneic hematopoietic cell transplant, however, these respiratory virus infections are not only very common but also often severe and sometimes deadly.
Allogeneic hematopoietic cell transplant is a therapy used to treat various types of blood cancers and other blood diseases. It involves first depleting cancerous or nonfunctional blood cells, then adding in stem cells from a healthy donor. The stem cells engraft and produce healthy, functional cells to replace the problematic ones.
While this therapy can be lifesaving, it presents new health challenges. The process of transplantation often requires significant immunosuppression so the patient’s immune system does not reject the foreign transplanted cells. Patients receiving transplants become highly susceptible to numerous conditions, including respiratory virus infections and chronic pulmonary impairment. Lung diseases like severe airflow obstruction and bronchiolitis obliterans syndrome, which cause difficulty breathing and fatigue, create significant disability and increase mortality among transplant recipients. Despite the burden of disease in this population, the role of post-transplant respiratory virus infections in the development of lung disease is poorly understood.
In a recent study published in The Journal of Infectious Diseases, researchers in the Boeckh lab and colleagues tackled the question of how respiratory virus infections contribute to lung impairment and mortality in people who recently received a hematopoietic cell transplant. There are many viruses that cause respiratory infections: human rhinoviruses (the predominant cause of the common cold), coronaviruses, influenza viruses, parainfluenza viruses, respiratory syncytial virus, and more. A major goal of the research was to determine which viruses are most associated with poor outcomes.
In the most comprehensive analysis of respiratory infections in people receiving hematopoietic cell transplant to date, the research team followed a cohort of 471 transplant recipients in the first year after transplant. Study participants completed symptom questionnaires and performed lung function measurements weekly. They were tested for a panel of 11 common respiratory viruses weekly during the first 100 days after transplant and whenever they experienced respiratory infection symptoms thereafter. Most of this cohort was tracked for an additional two years for pulmonary impairments such as obstructed airflow and bronchiolitis obliterans syndrome.
The study found that most (62%) participants had at least one respiratory virus infection in the year following stem cell transplant. Infections with human rhinovirus were the most common, though these were not significantly associated with long-term lung impairment. Infections with respiratory syncytial virus (RSV), however, were strongly associated with the development of bronchiolitis obliterans syndrome, an often-fatal progressive condition characterized by lung inflammation and scarring. The study also found that respiratory infections due to parainfluenza (PIV) were associated with airflow obstruction and infections due to influenza were associated with increased mortality within three years of transplant.
All this shows that the virus behind the infection matters – different viruses have different impacts on lung function. Dr. Guang-Shing Cheng, lead researcher on the study, commented that, “the association of specific viruses, namely RSV with bronchiolitis obliterans syndrome and PIV with late airflow obstruction, provides strong evidence that these viruses are implicated in the pathogenesis of lung disease in hematopoietic cell transplantation.” For now, these results can inform clinicians on how to improve care for patients who develop infections with viruses like RSV, PIV, or influenza. This may mean closer monitoring of lung function or lengthened antiviral treatment courses when available. But Cheng indicated that the results won’t end here. “We want to take this observation back to the lab to figure out how these viruses actually cause airway disease.”
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. Guang-Shing Cheng, Alpana Waghmare, Paul Carpenter, Larry Corey, Brenda Sandmaier, Keith Jerome, Wendy Leisenring, Janet Englund, and Michael Boeckh contributed to this research.
The spotlighted research was funded by The National Institutes of Health, MedImmune, and Seattle Children’s Center for Clinical and Translational Research.
Cheng GS, Campbell AP, Xie H, Ogimi C, Waghmare A, Kuypers J, Nichols WG, Carpenter P, Corey L, Callais C, Sandmaier BM, Stevens-Ayers T, Jerome KR, Chien JW, Leisenring WM, Englund JA, Boeckh M. 2025. Respiratory Virus Infections and Pulmonary Impairment after Allogeneic Hematopoietic Cell Transplantation. The Journal of Infectious Diseases. doi: 10.1093/infdis/jiaf503
Science Spotlight writer Ashley Person is a PhD candidate in the Cohn lab in the Vaccine and Infectious Disease Division at Fred Hutch. She studies how HIV-infected cells persist over time in people living with HIV on long term treatment.