A common, normally dormant virus can make matters worse for patients with critical illness - and a new study hints that preventing the virus from reawakening in these critical moments could stem some of its harm.

More than half of people in the U.S. harbor cytomegalovirus, or CMV, which usually lies dormant, showing no signs or symptoms and doing no harm. In those with suppressed immune systems, however, such as organ-transplant recipients or cancer patients receiving a bone-marrow transplant, the virus can reactivate and cause severe infections - or even death.

Research has shown that CMV also may play a role in the fate of critically ill patients with “normal” immune systems. In these patients, if the virus reactivates from its latent state, it is associated with worse outcomes - but it was unclear whether the virus makes matters worse for these patients or is an innocent bystander, just along for the ride.

New findings from a study led by researchers at Fred Hutchinson Cancer Research Center and the University of Washington suggest that preventing the virus from reactivating in critically ill, CMV-positive patients with normal immune systems could prevent severe CMV-associated complications.

The study, published Aug. 22 in the Journal of the American Medical Association, was based on data from 160 ICU patients treated for trauma or sepsis, a life-threatening type of infection that happens when the body’s immune response rages out of control. The research team, led by UW organ transplant and infectious disease researcher Dr. Ajit Limaye and Fred Hutch infectious disease specialist Dr. Michael Boeckh, split the study volunteers into two groups — half received a placebo and half received ganciclovir, a potent antiviral drug that’s often used to treat or prevent CMV reactivation in transplant patients.

“The question is always with observational studies, what’s the chicken and what’s the egg?” Boeckh asked. “Do they get the virus because they are critically ill and it’s just an indication of being ill, or does the virus really cause additional harm?”

The researchers’ phase 2 trial looking at ganciclovir use in this population was not large enough to address whether the antiviral drug could significantly reduce deaths from sepsis or trauma by reducing the burden of CMV. The study instead asked whether a biomarker of inflammation, known as IL-6, changed in patients treated with the antiviral.

The biomarker levels did not significantly change, they found, but their study uncovered some interesting findings that make the researchers want to keep pursuing this strategy:

• Patients who received the antiviral were less likely to have CMV reactivation and the drug also reduced the levels of the virus in the blood.
• The drug appeared to be safe in these patients.
• The group of patients who received ganciclovir also spent significantly fewer days on a ventilator during their stays in the ICU, suggesting that the drug could reduce lung injury in this group. Other research teams have seen a similar effect in an animal model - treating CMV-positive mice with an antiviral reduces damage to their lungs from sepsis, Limaye said.

Although these hints are exciting, there’s not yet enough evidence to suggest that ICU patients should be routinely treated with ganciclovir. That decision should hinge on a much larger data set, the researchers said. They’re planning to launch a larger trial with enough study participants to capture a true difference in clinical outcomes from treating with the antiviral.

Both Boeckh and Limaye were thrilled that their careers spent treating small but vulnerable populations - bone marrow and organ transplant recipients, respectively - could potentially have a meaningful impact on a much larger group of patients in need of better treatments.