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Persistent immune dysregulation after sepsis associated with worse long-term outcomes

Persistent dysregulated immune response after hospital discharge, which was common among patients who were hospitalized for sepsis, may increase the risks for hospital readmission and death, according to data published in JAMA Network Open.

Sachin Yende, MD, MS, professor of critical care medicine and clinical and translational science at University of Pittsburgh School of Medicine, and vice president of critical care and deputy chief of staff at the Veterans Affairs Pittsburgh Healthcare System, and colleagues included 483 patients (mean age, 60.5 years; 54.9% men) who survived hospitalization for sepsis from 2012 to 2017 at multiple centers. During 1-year follow-up, 485 readmissions occurred in 205 patients (42.5%), with a median time to first readmission of 63 days. Among those readmitted, 49.3% were readmitted once, 19% were readmitted twice and 31.7% were readmitted at least three times. The most common causes for readmission were infection (49.9%), cardiovascular disease (9.6%) and cancer (4.5%).

Also during follow-up, 8.9% of patients died by 3 months, 11.6% died by 6 months and 17.6% died by 12 months. Common causes again included cancer (46.4%), infection (23.2%) and CVD (17.4%).

Many patients included in the study had elevated circulating inflammatory biomarkers after hospital discharge. Interleukin-6 (IL-6) levels were elevated in 74.2% of patients at 3 months, 70.5% at 6 months and 66.3% at 12 months, and high-sensitivity C-reactive protein (hs-CRP) levels were elevated in 25.8% of patients at 3 months, 30.2% at 6 months and 25.6% at 12 months. Similarly, levels of soluble PD-L1 were also elevated in 46.4% of patients at 3 months 44.9% at 6 months and 49.4% at 12 months.

Based on the trajectories of hs-CRP and soluble PD-L1, the researchers identified two common phenotypes. The hyperinflammation and immunosuppression phenotype, which accounted for 68.3% of patients, included those who had high hs-CRP and soluble PD-L1 levels, and the normal phenotype, which accounted for 29.6% of patients, included those with normal hs-CRP and soluble PD-L1 levels. Patients within these phenotypes had similar clinical characteristics and in-hospital course for sepsis, according to the data.

When compared with normal phenotype, the hyperinflammation and immunosuppression phenotype had a greater risk for 1-year mortality (adjusted OR = 8.26; 95% CI, 3.45-21.69), 6-month all-cause readmission or mortality (aHR = 1.53; 95% CI, 1.1-2.13) and 6-month readmission or mortality attributable to CVD (subdistribution HR = 5.07; 95% CI, 1.18-21.84) or cancer (subdistribution HR = 5.15; 95% CI, 1.25-21.18).

Results remained strong after adjustment for demographic characteristics, chronic diseases, illness severity, organ support and infection site during sepsis hospitalization and in sensitivity analyses, the researchers noted.

“The dysregulated host immune response activated during sepsis may persist up to 1 year. Individuals with persistent biomarkers of inflammation and immunosuppression had a higher risk of readmission and death due to cardiovascular disease and cancer compared with those with normal circulating biomarkers,” the researchers wrote. “Our findings suggest that long-term immunomodulation strategies should be explored in patients hospitalized with sepsis.”– by Melissa Foster

Disclosures: Yende reports he received personal fees from Atox Bio and grants from Bristol-Myers Squibb and Roche outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.