The life-threatening infection sepsis remains a leading cause of death in hospitals. According to a recent study, PCR has been used to spot latent viruses that lay dormant in the body and are reactivated in sepsis. This provides evidence to support a controversial theory that patients with sepsis progress to an immunosuppressed state.

Richard Hotchkiss and Gregory Storch

When people are healthy, the immune system keeps latent viruses in check. However, according to research at Washington University School of Medicine in St Louis, the viruses begin to re-emerge and re-enter the bloodstream when sepsis lingers for more than a few days, suggesting that the original infection has suppressed the immune system. This state is particularly dangerous for patients who are very ill and vulnerable to secondary infections, such as pneumonia associated with being on a ventilator.

“A controversy has existed over whether patients with sepsis progress to a state of immune suppression,” said Gregory Storch of the School of Medicine. “The finding that critically ill patients with sepsis have a number of different viruses circulating in the bloodstream is compelling evidence they are immune-suppressed and dramatically could alter therapy for sepsis.”

The researchers took serial whole blood and plasma samples from 560 critically-ill septic patients treated in the surgical and medical intensive care units at Barnes-Jewish Hospital, with 161 critically-ill non-septic, and 164 healthy age-matched patients as comparisons. The team used quantitative-polymerase-chain-reaction (qPCR) to look for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes simplex (HSV), human herpes virus-6 (HHV-6), and torque teno virus (TTV). The team also determined levels of polyomaviruses BK and JC in urine.

“We were looking for viruses that people are commonly exposed to early in life and that persist in the body in a latent form that doesn’t cause sickness,” said Storch. “No one had really looked at this in a comprehensive fashion before. These viruses have the potential to reactivate if the immune system is suppressed.”

The levels of virus were assessed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. The team found that the patients with protracted sepsis had a marked increase in frequency of detectable virus, compared with the healthy controls and critically ill patients without sepsis. Among the sepsis patients, for example, the researchers found that 53% had Epstein-Barr virus, 24% had cytomegalovirus, 14% had herpes-simplex virus, and 10% had human herpes simplex virus-7.

In a subgroup of 209 sepsis patients tested for all viruses, 54% were positive for two or more. The septic patients with higher levels of viruses detected in their blood were more likely than critically ill patients without sepsis to have more severe illnesses, secondary fungal and bacterial infections, and longer stays in the intensive care unit. The researchers also saw that the reactivation of latent viruses was common with prolonged sepsis, at similar levels to those seen in immunosuppressed patients. It’s not yet clear from this research whether reactivated latent viruses contribute to morbidity and mortality in sepsis. The research was published in PLOS One.

Sepsis graph

Source: PLoS One

“We stumbled onto more viruses than we expected, and we don’t know yet whether some of these viruses are causing problems in their own right,” Storch said. “We think this paper will stimulate others to carry out further investigations of the role of latent viruses in sepsis.”

“This is an indicator of the degree of immune suppression in septic patients, and it tells us they are highly immune-suppressed,” explained Richard S Hotchkiss, professor of anaesthesiology.

If this theory is further supported, the emergence of latent viruses could be used as a way to monitor the immune status of patients with sepsis, track its severity, and guide treatment. Immunotherapeutics that stimulate the immune system could potentially support the treatment of prolonged sepsis, and the Washington University team is planning several clinical trials of such drugs in sepsis patients.