Assessment of a cellular host response test to risk-stratify suspected COVID-19 patients in the Emergency Department setting

O’Neal, Hollis R.; Sheybani, Roya; Caffery, Terrell; Hamer, Diana; Laperouse, L. Mark; Musso, Mandi W.; O’Neal, Catherine; Tse, Henry T. K.; Shah, Ajay; Thomas, Christopher

doi:10.1371/journal.pone.0264220

Cited by 5 publications

(5 citation statements)

References 43 publications

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“…The ISI is pathogen agnostic test, providing rapid risk stratification independent of the pathogen, as suggested by the ISI’s ability to risk stratify patients early in the COVID-19 pandemic ( 25 ). A list of potential pathogens identified through various diagnostic methods is presented in S1-Table 6 ( http://links.lww.com/CCX/B289 ).…”

Section: Discussionmentioning

confidence: 99%

“…Details of performing the IntelliSep test ( 20 ) can be found in the Supplemental Material ( http://links.lww.com/CCX/B289 ). The IntelliSep result is reported as the ISI, a single number ranging from 0.1 to 10.0, divided into three prespecified interpretation bands using limits of less than equals to 4.9 (band 1) and greater than or equal to 6.3 (band 3), with band 2 intervening ( 25 ).…”

Section: Methodsmentioning

confidence: 99%

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Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use

O’Neal,

Sheybani,

Janz

et al. 2024

Critical Care Explorations

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OBJECTIVES: To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis. DESIGN: Prospective cohort study. SETTING: Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington. PATIENTS: Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection. INTERVENTIONS: All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians. MEASUREMENTS AND MAIN RESULTS: Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5–15.7%) in band 1, 28.1% (95% CI, 21.3–35.8%) in band 2, and 49.4% (95% CI, 41.4–57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization. CONCLUSIONS: Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use

O’Neal,

Sheybani,

Janz

et al. 2024

Critical Care Explorations

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“…Previously, we have demonstrated the performance of the IntelliSep test and its corresponding ISI as an early diagnostic test for sepsis and in risk-stratifying patients with signs or suspicion of infection in the emergency department [ 30 , 32 ]. The findings in this study provide evidence to support a connection between the biophysical measurements observed in the IntelliSep test and biological phenomena occurring during leukocyte activation in a dysregulated host response to infection and sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…The test yields an IntelliSep Index (ISI) in under ten minutes, a score between 0.1–10.0 that is stratified into three discrete interpretation bands based on probability of sepsis: Band 1, Band 2, and Band 3 [ 30 ]. The diagnostic performance of the IntelliSep test when applied to patients presenting to the ED with signs or suspicion of infection was previously evaluated in several clinical studies [ 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Biophysical Changes of Leukocyte Activation (and NETosis) in the Cellular Host Response to Sepsis

et al. 2023

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Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a cohort of subjects was segregated into Control and Diseased populations and tested for levels of NET components (citrullinated histone (cit-H3) DNA and neutrophil elastase (NE) DNA) using customized ELISA assays and correlated with ISI scores from the same patient samples. Significant increases in IntelliSep Index (ISI) scores were observed with increasing concentrations of PMA in healthy blood (0 and 200: p < 10−10; 0 and 400: p < 10−10). Linear correlation was observed between the ISI and quantities of NE DNA and Cit-H3 DNA in patient samples. Together these experiments demonstrate that the IntelliSep test is associated with the biological processes of leukocyte activation and NETosis and may indicate changes consistent with sepsis.

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“…Once applied to a standardized population, the results of a diagnostic could be more easily applied in protocolized care and/or care pathways. Integration of a sepsis diagnostic such as IntelliSep into clinical management could potentially impact a variety of aspects in sepsis care including patient outcomes, resource utilization, and antimicrobial stewardship [29]. Indeed, a recent costs and consequences modeling study found that the IntelliSep test has the potential to both lower mortality and lower costs of care on average relative to a strategy employing Procalcitonin [30].…”

Section: Discussionmentioning

confidence: 99%

Variability in Provider Assessment of Sepsis and Potential of Host Response Technology to Address this Dilemma—Results of an Online Delphi Study

Kraus,

O’Neal,

Ledeboer

et al. 2023

JPM

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Potentially septic patients have a huge clinical and economic impact on hospitals and often present to the emergency department (ED) with undifferentiated symptoms. The triage of these patients is complex and has historically relied heavily upon provider judgment. This study aims to evaluate the consistency of provider judgment and the potential of a new host response sepsis test to aid in the triage process. A modified Delphi study involving 26 participants from multiple specialties was conducted to evaluate provider agreement about sepsis risk and to test proposed actions based on the results of a sepsis test. The participants considered case vignettes of potentially septic patients designed to represent diagnostic dilemmas. Provider assessment of sepsis risk in these cases ranged from 10% to 90% and agreement was poor. Agreement about clinical actions to take in response to testing improved when participants considered their own hypothetical borderline cases. New host response testing for sepsis may have the potential to improve sepsis diagnosis and care and should be applied in a protocolized fashion to ensure consistency of results.

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Assessment of a cellular host response test to risk-stratify suspected COVID-19 patients in the Emergency Department setting

Cited by 5 publications

References 43 publications

Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use

Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use

Biophysical Changes of Leukocyte Activation (and NETosis) in the Cellular Host Response to Sepsis

Variability in Provider Assessment of Sepsis and Potential of Host Response Technology to Address this Dilemma—Results of an Online Delphi Study

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