Good News: Stemming the harm common virus causes in critically ill patients

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Dr. Michael Boeckh
Dr. Michael Boeckh Photo by Robert Hood / Fred Hutch News Service

Common virus can be deadly in the ICU

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 JAMA, 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. Sepsis is a highly deadly condition, the researchers said, with mortality rates of 20 to 30 percent. And it’s common, affecting more than a million patients per year in the U.S.

“It’s exciting to think about translating what we’ve learned in the immunocompromised setting to a population that is orders of magnitude greater,” Limaye said.

The National Institutes of Health funded the study, and the biotech company Genentech supplied the antiviral drug used in the research.

— Rachel Tompa / Fred Hutch News Service

Dr. Raphael Gottardo
Dr. Raphael Gottardo Photo by Robert Hood / Fred Hutch News Service

Fred Hutch-led computational study on HIV vaccine wins Mitchell Prize

A  Fred Hutchinson Cancer Research Center-led study uncovering the role of rare immune cells in a working HIV vaccine has won the Mitchell Prize, an annual award given by the International Society for Bayesian Analysis. Fred Hutch computational biologist Dr. Raphael Gottardo led the study, which was published in the journal Nature Biotechnology May 25, 2015. The prize is awarded to a paper that uses Bayesian analysis, a type of statistical approach, to solve an applied problem.

“We knew the paper was already having a significant impact in the vaccine field, but it’s nice to see it be recognized by our peers, i.e., statisticians,” said Gottardo, a member of the Vaccine and Infectious Disease Division at the Hutch.

Gottardo, who is also part of the HIV Vaccine Trials Network headquartered at the Hutch, led an international research team that devised a unique, computational method to sift through the immune cells and their importance in HIV-vaccine recipients. Using that method, the team found that a certain type of T cell — known as “polyfunctional T cells” for their ability to produce several different immune molecules — was linked to a lower risk of infection.

Because of that finding, trials run through the HVTN since the paper was published now incorporate tests for this special class of T cells to help the researchers screen new candidate HIV vaccines faster and know which candidate vaccines are eliciting a potentially protective immune response.

“[It helps] us understand what are the things that we need to make a better vaccine,” Gottardo said in a previous interview.

— Rachel Tompa / Fred Hutch News Service

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