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 programmes 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 per cent of sepsis survivors die within a year of leaving hospital, with a further six to eight per cent 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 and funded by the National Institute for Health and Care Research (NIHR), 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 re-hospitalisations in adults who had survived sepsis.
The findings were published in Science Translational Medicine.
The long-term health impacts of sepsis survivors may not be receiving enough attention in health care. In the UK, one in three sepsis survivors are re-hospitalised within 90 days, with the majority of these re-hospitalisations from infections, and one in six patients are 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.
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 from recurrent infections.
While sepsis survivors may receive vaccinations as part of established vaccination programmes (such as flu or pneumonia vaccinations for older adults), vaccinations are not part of standard of care for sepsis survivors.
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 re-hospitalisation with infection or death.
Overall, the vaccine did not reduce re-hospitalisation 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 altered immune system before vaccination.
The findings suggest that established vaccination programmes 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.
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.
Professor Shankar-Hari
Professor Shankar-Hari's work at King's College London, where he is Director of the King's Health Partners' Centre 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.
Professor Waljit Dhillo, Dean of the NIHR Academy
The work was funded by an NIHR Fellowship awarded to Professor Manu Shankar-Hari.
