HHV-6B lung infection doubles the mortality rate of transplant patients with respiratory disease

Investigators at the Fred Hutchinson Cancer Research Center and University of Washington in Seattle have found that human herpesvirus 6B in lung fluid of bone marrow transplant recipients with pneumonia is associated with a 2-fold increased risk of death. Importantly, HHV-6B  positive patients who were treated with an antiviral had a 60% lower risk of death.

Joshua Hill, MD and Michael Boeckh, MD, PhD of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center

The study was led by Joshua Hill, MD, and Michael Boeckh, MD, PhD, in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center. The team tested lung fluid from 553 patients over a 23-year period between 1992 and 2015 and found HHV-6B in 27% of samples. The authors also found that higher viral load correlated with increased mortality, whereas lower levels likely represented asymptomatic HHV-6B ‘shedding’.

The group also measured HHV-6 gene expression in lung tissue samples using a novel RNA in situ hybridization assay. This demonstrated evidence of active viral infection in each of three patients tested.  

HHV-6B reactivation has previously been associated with lower respiratory tract disease (LRTD) following bone marrow transplantation, but unlike its close relative CMV, it has not been identified as a pulmonary pathogen. For this reason, many potentially treatable cases of HHV-6B pneumonia are currently missed because testing for HHV-6B is not routine. Patients with presumed non-infectious causes of pneumonia (e.g. ‘idiopathic pneumonia syndrome’) are treated with steroids, which could exacerbate an active HHV-6B infection. As a result, recognizing HHV-6B as a lung pathogen could improve outcomes.

The subset of patients categorized as having “idiopathic” pneumonia accounted for 17% of 685 transplant patients with lower respiratory tract disease. HHV-6B was identified in 30 out of 118 (25%) in this category.

In terms of next steps, the researchers note that a clinical trial is needed to help support the conclusions from this study, either a trial that focuses on improved detection of HHV-6B in lung fluid of transplant patients with pneumonia, or a treatment trial to prevent HHV-6B from reactivating.

Additional support for the designation of HHV-6B as a lung pathogen came recently from researchers at the University of Michigan who demonstrated that a murine homolog of HHV-6B reactivates after transplantation and induces a condition similar to ‘idiopathic pneumonia syndrome’ in mice. They also found that early HHV-6 infection increased the risk of idiopathic pneumonia in transplant patients (Zhou 2019).

The study was supported by a pilot grant from the HHV-6 Foundation, as well as the National Institute of Allergy and Infectious Disease and the American Society for Blood and Marrow Transplantation.The full text can be found in the October 10th 2019 issue of the Journal of Clinical Oncology. Human Herpesvirus 6B and Lower Respiratory Tract Disease After Hematopoietic Cell Transplantation