Sepsis survivors show widely varied vaccine responses in clinical trial

People who have survived sepsis don’t respond to vaccines in the same way as those who haven’t had sepsis, according to new clinical trial results. The findings suggest more work is needed to understand why the vaccine-related immune response is altered in sepsis survivors so that vaccination programs can be tailored to reduce sepsis survivors’ risk of infections and improve long-term health outcomes.

People who have survived intensive care unit admission with sepsis—known as sepsis survivors—can have a weakened or altered immune system, which can increase the risk of new infections and death. Fifteen percent of sepsis survivors die within a year of leaving the hospital, with a further 6% to 8% dying every year over the next five years.

The VACIRiSS trial, led by King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, found that a vaccine that helps protect against serious illnesses like pneumonia and meningitis in the general population did not reduce the risk of future infections or rehospitalizations in adults who had survived sepsis. The findings were published in Science Translational Medicine.

A high-risk recovery period

“The long-term health impacts of sepsis survivors may not be receiving enough attention in health care. In the U.K., 1 in 3 sepsis survivors is rehospitalized within 90 days, with the majority of these rehospitalizations resulting from infections, and 1 in 6 patients is no longer alive at the end of the first year after recovering from sepsis. Despite this, there is no routine long-term follow-up care for sepsis survivors in the NHS,” said Professor Manu Shankar-Hari, professor of critical care medicine at King’s College London and principal investigator on the trial.

Sepsis is a misfiring of immune responses to a bacterial, viral, fungal or other infection. If not treated quickly, sepsis can cause failure of vital organs and death. Globally, it’s estimated that there are about 166 million sepsis cases and 21 million deaths from sepsis each year. Those who survive (approximately 145 million patients globally every year) are at increased risk of long-term ill health, including recurrent infections.

While sepsis survivors may receive vaccinations as part of established vaccination programs (such as flu or pneumonia vaccinations for older adults), vaccinations are not part of the standard of care for sepsis survivors.

Trial results showed mixed immunity

In the trial, 214 sepsis survivors were randomly assigned to receive a vaccine, called PCV13, or a placebo injection. Participants were followed up for a year to see whether the vaccine reduced their risk of rehospitalization with infection or death.

Overall, the vaccine did not reduce rehospitalization with infection or death in sepsis survivors. While blood tests showed that many participants did produce immune responses to the vaccine, the responses varied widely from person to person. The differences in vaccine responses were linked to factors such as age, body weight, sex and levels of immune system alteration before vaccination.

The findings suggest that established vaccination programs may need to be modified to provide better protection to sepsis survivors. However, more needs to be done to understand the varied responses in sepsis survivors to inform what changes are needed.

Calls for post-sepsis investment

“Our findings show there is a need for investment in post-sepsis care and in research to better understand how the altered immune response could be targeted to improve outcomes for this vulnerable population,” said Shankar-Hari.

Shankar-Hari’s work at King’s College London, where he is director of the King’s Health Partners’ Center for Critical Illness Research, aims to advance understanding of the altered immune system in sepsis and other critical illnesses. He is also chair of an international commission, led by King’s Health Partners and The Lancet, focused on improving the diagnosis, management and treatment of sepsis.

“Investing in future research leaders is vital because their work helps us understand complex health problems and how we can begin to address them. For 20 years, the NIHR has supported talented researchers to develop the evidence needed to improve health and care. Research like this could ultimately help improve care and outcomes for people who have survived sepsis,” said Professor Waljit Dhillo, dean of the NIHR Academy.

Who’s behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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