(A) Schematic of study cohort. Serum samples were collected from patients from the University of Chicago hospital’s Medical Intensive Care Unit who matched the clinical definition of sepsis. Control samples were obtained from age-matched, healthy control individuals. (B) Box plot depicting the serum levels of PLA2G5 in septic patients with the sequential organ failure assessment (SOFA) scores of ≤ 7 versus ≥ 8. Box edges, interquartile range; middle line, median. **P < 0.01 by 2-tailed Student’s t test. (C) Correlation between the serum levels of PLA2G5 in patients with bacterial, fungal, or viral sepsis as indicated (colors) and SOFA score (data from B). Dots outlined in black indicate samples from patients who died from sepsis. (D) Schematic of study cohort in public blood proteomic data from patients with COVID-19. A1 is the most severe group and A5 is the least severe group. ED, Emergency Department. (E) Box plots depicting log₂ relative fluorescence units of PLA2G5 level in plasma of patients with COVID-19 by severity over time (see Methods). Patients were classified by acuity levels based on the WHO Ordinal Outcomes Scale. Acuity levels were determined by their severity condition within 28 days after enrollment as follows: A1, death within 28 days; A2, intubation, mechanical ventilation; A3, hospitalized and requiring supplemental oxygen; A4, hospitalized without requiring supplemental oxygen; and A5, discharged directly from the Emergency Department without subsequently returning and requiring admission within 28 days. A1–A2 were classified as sepsis (dark grey) and A3–A5 as nonsepsis (white). Box edges, interquartile range; middle line, median. (F) Distribution of accuracy values from a decision tree classifier analysis using PLA2G5 plasma levels at day 0 from sepsis and nonsepsis patient groups (data from E).