TABLE 2.

Candidate protein biomarkers

	Description	Limitations
Interleukin-6 (IL-6)	Prototypical cytokine involved in many pro-inflammatory states, associated with comparatively poor prognosis in the setting of sepsis and SIRS. Numerous IL-6 inhibitor therapies approved for auto-inflammatory conditions.	Broadly pro-inflammatory and nonspecific for infectious states.
Pro-adrenomedullin (Pro-ADM)	Serum stable pro-peptide of adrenomedullin. Proposed to function similarly to procalcitonin.	Primarily related to vascular dysregulation; no well-accepted cutoffs.
Pancreatic stone protein (PSP)	Glycoprotein, associated with sepsis severity. Has been studied to differentiate infectious states in burn patients.	Limited data, has not been shown to outperform existing single biomarkers.
Myxovirus resistance protein A (MxA)	Protein elevated in the setting of acute viral infections and myositis. Utilized in FebriDx point-of-care device.	Limited data as a single biomarker to differentiate infection. Associated with connective tissue autoimmune diseases.
sTREM-1	Cell surface receptor expressed on monocytes, macrophages, and neutrophils. Expressed in states of bacterial, fungal, viral, and parasitic infection, particularly sepsis. Associated with septic shock and poor malarial prognosis.	Poor ability to differentiate a specific infectious etiology of sepsis.
TNF-related apoptosis-inducing ligand (TRAIL)	Protein ligand cytokine produced by most tissues, elevated in viral infection compared to bacterial infection. Also studied as the target for cancer immunotherapy. Utilized in the MeMed BV test.	Limited data as a single biomarker for measuring the host response to infection.