Science Spotlight

Is the common cold a risk for hematopoietic cell transplant recipients?

From the Boeckh laboratory, Vaccine and Infectious Disease Division

Human rhinovirus (HRV) is a common cause of viral respiratory infections. Even though the virus is associated with the common cold, and is mild in most people, viral infiltration often causes more harm in immunocompromised individuals. In a paper by the Boeckh lab at Fred Hutch (Vaccine and Infectious Disease Division) the effects of HRV in the lower respiratory tract were studied for increased risk of mortality in hematopoietic cell transplantation (HCT) candidates. In a paper published in Haematologica, the group used modern molecular techniques to better identify and study HRV infection, looking at HRV RNA in the bronchoalveolar lavage (BAL) fluid. In order to investigate the potential of HRV as a significant pathogen in immunocompromised patients, the group investigated mortality of patients with HRV in the lower respiratory tract (LRT) as compared to the upper respiratory tract (URT), the effect of co-pathogen infiltration on HRV outcomes, as well as risk factors for mortality.

Kaplan-Meier estimated of overall survival by pathogen (N=222, p=0.62). Figure provided by Dr. Waghmare

The researchers divided a cohort of 697 HRV positive patients into two groups, one with URT infections (569, 82%) and a second with LRT infections (128, 18%). Of 697 patients, about half had other co-pathogens. Looking closer at the LRT infection group, the researchers found the probabilities of 90-day survival after HRV infection to be 55%, and 64% if a co-pathogen was present (Figure 1). Looking at overall mortality within this group, factors significantly associated with higher mortality were low monocyte count, need for oxygen and steroid use. If only respiratory failure was analyzed for risk, low monocyte count and steroid use were significant factors.

The researchers also looked for HRV RNA in the BAL fluid, looking for a link between viral RNA amount and its effect on mortality. Unfortunately, the amount of RNA present was not significantly associated meaning that there was not a link between high viral load and mortality. Looking closely at 20 patients with sequential BALs within 90 days of diagnosis of LRT infection, the authors of the 14 patients with decreasing viral load 6 dies and a 6 patients that had maintained or increased virus died. This suggest that sequential maintenance or increase in viral load may lead to mortality. To augment the BAL PCR data the group looked at LRT biopsy/autopsy samples from 22 patients. Of theses, 21 were positive by PCR and 6 were culture positive for HRV. Of the 52 that died in the HRV LRT group 12 were autopsied and 50% were positive for HRV by PCR. This data supports the link between mortatiltiy of paitens and HRV. In comparing mortality by HRV to other viral respiratory infections like influenza and RSV, the team found that mortality remained similar between all groups. They also found that mortality in patients with or without a co-pathogen were similar, suggesting HRV infection itself is causing the pathology; otherwise co-infections should result in worse outcomes.

In conclusion, the group found that HRV infection outcome in HTC patients was similar to other viral pathogens. They document HRV RNA in the BAL and found that to be clinical important, however the amount was not associated with mortality which is similar to other findings with other viral pathogen. Senior author, Dr. Boeckh, stated, “this study strongly suggests that human rhinovirus can be a pulmonary pathogen in HCT recipients. It provides the rationale for further studies to identify risk factors for progressive pulmonary disease as well as for the development of therapeutics”.

Funding for this work was provided by the National Institutes of Health.

Seo S,Waghmare A,Scott EM,Xie H,Kuypers JM,Hackman RC,Campbell AP,Choi SM,Leisenring WM,Jerome KR,Englund JA,Boeckh M. 2017. Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients association with mortality. Haematologica. pii: haematol.2016.153767. doi: 10.3324/haematol.2016.153767.