In the Journals

Persistent inflammation in sepsis survivors linked to death, readmission

Around two-thirds of patients in a 5-year, multisite study who survived hospitalization for sepsis demonstrated persistent elevated levels of inflammation and immunosuppression biomarkers for up to 1 year, placing them at risk for worse long-term outcomes, including death or readmission, researchers found.

Approximately one in three patients who survive sepsis die within a year, so sepsis survivors “aren’t out of the woods yet,” Sachin Yende, MD, MS, professor of critical care medicine and clinical and translational science at the University of Pittsburgh School of Medicine and vice president of critical care and deputy chief of staff at the VA Pittsburgh Healthcare System, said in a news release.

Yende and colleagues conducted a prospective, multicenter cohort study to evaluate if there is a persistence of “abnormalities” in the host immune response after discharge.

The study was conducted in 12 United States hospitals and included 483 adult patients who survived a hospitalization for sepsis from Jan. 10, 2012, to May 25, 2017. They followed the patients for up to 1 year and measured circulating levels of inflammation, immunosuppression, endothelial dysfunction and oxidative stress biomarkers five times during and after hospitalization.

Readmissions were common, with the researchers reporting 485 readmissions among 205 patients.

By 3 months, 8.9% of patients had died, 25.8% had elevated high-sensitivity C-reactive protein (hs-CRP) levels, and 46.4% had elevated soluble programmed death ligand 1 (sPD-L1) levels, according to Yende and colleagues. By 6 months, 11.6% of patients had died, 30.2% had elevated hs-CRP levels, and 44.9% had elevated sPD-L1 levels. By 12 months, 17.6% patients had died, 25.6% had elevated hs-CRP levels, and 49.4% had elevated sPD-L1 levels.

The researchers also identified two common phenotypes based on hs-CRP and sPDL1 trajectories. According to the study, 68.3% of patients had high hs-CRP and sPDL1 levels (referred to as hyperinflammation or immunosuppression phenotype) and 30% had normal hs-CRP and sPDL1 levels (normal phenotype). The researchers noted that clinical characteristics and clinical course during hospitalization were similar between the two phenotypes.

However, they found that patients with hyperinflammation or immunosuppression phenotype had higher 1-year mortality (odds ratio [OR] = 8.26; 95% CI, 3.45-21.69) higher 6-month all-cause readmission or mortality (hazard ratio [HR] = 1.53; 95% CI, 1.10-2.13) and higher 6-month readmission or mortality attributable to cardiovascular disease (HR = 5.07; 95% CI, 1.18-21.84) or cancer (HR = 5.15; 95% CI, 1.25-21.18) compared with patients with the normal phenotype.

“One piece that may be of interest for ID physicians is that pneumonia and sepsis have been linked to cardiovascular disease (heart disease and stroke),” Yende told Infectious Disease News. “We showed that persistent inflammation increased risk of cardiovascular readmissions and death in our study. Thus, our findings may explain why severe infections or sepsis may be linked to [a] higher risk of cardiovascular events.”

According to Yende, C-reactive protein lab tests are “easily available” and can be used to identify patients who survived sepsis hospitalization but are at risk for poor long-term outcomes, such as death and readmission.

“Future research should understand why (the mechanism of) inflammation persists for a year,” Yende said. “This research will help identify new therapies to improve long-term outcomes of sepsis patients.” - by Marley Ghizzone

Disclosures: Yende reports receiving 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.

Around two-thirds of patients in a 5-year, multisite study who survived hospitalization for sepsis demonstrated persistent elevated levels of inflammation and immunosuppression biomarkers for up to 1 year, placing them at risk for worse long-term outcomes, including death or readmission, researchers found.

Approximately one in three patients who survive sepsis die within a year, so sepsis survivors “aren’t out of the woods yet,” Sachin Yende, MD, MS, professor of critical care medicine and clinical and translational science at the University of Pittsburgh School of Medicine and vice president of critical care and deputy chief of staff at the VA Pittsburgh Healthcare System, said in a news release.

Yende and colleagues conducted a prospective, multicenter cohort study to evaluate if there is a persistence of “abnormalities” in the host immune response after discharge.

The study was conducted in 12 United States hospitals and included 483 adult patients who survived a hospitalization for sepsis from Jan. 10, 2012, to May 25, 2017. They followed the patients for up to 1 year and measured circulating levels of inflammation, immunosuppression, endothelial dysfunction and oxidative stress biomarkers five times during and after hospitalization.

Readmissions were common, with the researchers reporting 485 readmissions among 205 patients.

By 3 months, 8.9% of patients had died, 25.8% had elevated high-sensitivity C-reactive protein (hs-CRP) levels, and 46.4% had elevated soluble programmed death ligand 1 (sPD-L1) levels, according to Yende and colleagues. By 6 months, 11.6% of patients had died, 30.2% had elevated hs-CRP levels, and 44.9% had elevated sPD-L1 levels. By 12 months, 17.6% patients had died, 25.6% had elevated hs-CRP levels, and 49.4% had elevated sPD-L1 levels.

The researchers also identified two common phenotypes based on hs-CRP and sPDL1 trajectories. According to the study, 68.3% of patients had high hs-CRP and sPDL1 levels (referred to as hyperinflammation or immunosuppression phenotype) and 30% had normal hs-CRP and sPDL1 levels (normal phenotype). The researchers noted that clinical characteristics and clinical course during hospitalization were similar between the two phenotypes.

However, they found that patients with hyperinflammation or immunosuppression phenotype had higher 1-year mortality (odds ratio [OR] = 8.26; 95% CI, 3.45-21.69) higher 6-month all-cause readmission or mortality (hazard ratio [HR] = 1.53; 95% CI, 1.10-2.13) and higher 6-month readmission or mortality attributable to cardiovascular disease (HR = 5.07; 95% CI, 1.18-21.84) or cancer (HR = 5.15; 95% CI, 1.25-21.18) compared with patients with the normal phenotype.

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“One piece that may be of interest for ID physicians is that pneumonia and sepsis have been linked to cardiovascular disease (heart disease and stroke),” Yende told Infectious Disease News. “We showed that persistent inflammation increased risk of cardiovascular readmissions and death in our study. Thus, our findings may explain why severe infections or sepsis may be linked to [a] higher risk of cardiovascular events.”

According to Yende, C-reactive protein lab tests are “easily available” and can be used to identify patients who survived sepsis hospitalization but are at risk for poor long-term outcomes, such as death and readmission.

“Future research should understand why (the mechanism of) inflammation persists for a year,” Yende said. “This research will help identify new therapies to improve long-term outcomes of sepsis patients.” - by Marley Ghizzone

Disclosures: Yende reports receiving 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.