C24-06 Host-response Score Improves Risk Stratification in Atypical Presentations of Suspected Acute Infection or Sepsis

Rationale Early and accurate risk assessment of patients with suspected acute infection or sepsis is particularly challenging in those with atypical presentations, such as elderly, immunocompromised, or comorbid patients or those who appear clinically stable. This is because nonspecific or mild decompensation may be caused by chronic disease, obscuring early infection-related organ dysfunction, leading to under- or over-triage. Standard-of-care (SOC) tools such as the Emergency Severity Index (ESI), quick Sequential Organ Failure Assessment (qSOFA), and lactate rely on overt physiologic or metabolic abnormalities and accordingly, show limited accuracy in these groups. MeMed Severity™ (MMSev), an FDA-designated Breakthrough Device, integrates three host-response proteins to generate a score indicating risk of progression to organ failure or death. We evaluated MMSev performance compared with ESI, qSOFA, and lactate across these challenging subgroups. Methods Adults ≥ 18 years with suspected infection or sepsis were enrolled at 35 sites across Urgent Care Centers (UCC), Emergency Departments (EDs), wards and ICUs for a discovery cohort. Patients included in the sub-groups analysis needed to be one or more of: clinically stable, elderly, comorbid and immunosuppressed. Clinically stable was defined as oxygen saturation ≥ 92% on room air, respiratory rate ≤ 22/min, and systolic blood pressure ≥ 100mmHg at presentation. Elderly were defined as ≥ 65 years. Comorbid was one or more of the following: hypertension, chronic heart failure, obesity, diabetes, COPD or malignancy. Immunocompromised was defined as having an active malignancy or immunosuppressive treatment. Severe outcome was defined as invasive mechanical ventilation, vasopressor support or dialysis within 72 hours, or death within 14 days from MMSEv testing. The area under the curve (AUC) was used to compare performance. Results A total of 1951 patients were included (age - median (IQR): 64.5 (45.0,76.2) years; 46.8% female). Enrolment setting was 74.5% ED, 13.0% wards, 9.6% UCC, 2.9% ICU. Overall, 15.9% experienced a severe outcome. In the entire cohort, MeMed Severity™ (MMSev) showed an AUC of 0.84 (95% CI, 0.81-0.87). Compared to available SOC data, MMSev demonstrated AUC values of 0.83, 0.77, and 0.81 versus qSOFA (0.72), ESI (0.64), and lactate (0.73), respectively. Across subgroups, MMSev consistently showed higher discriminative performance, with AUC differences ranging from 0.07 to 0.23 in favor of MMSev (Table 1). Conclusions MMSev provides enhanced risk stratification for organ failure and mortality in patients with atypical presentations of suspected acute infection or sepsis, addressing key gaps of SOC tools. MMSev may support earlier, more targeted management.