RESUMO
OBJECTIVE: To develop a novel whole-blood epigenetic biomarker of immune system status, or EpiMarker, that would indicate whether a person with a recent COVID-19 diagnosis is at risk for severe symptoms including Acute Respiratory Distress Syndrome. METHODS: Using a novel methyl-sensitive restriction endonuclease approach to measure site-specific DNA methylation profiles, immune system phentoype EpiMarkers are identified using a machine-learning computational bioinformatics platform. The result is a diagnostic network of 20 to 40 immuno DNA methylation sites having the greatest predictive power for identifying patients whose COVID-19 disease will likely progress to ARDS requiring ICU/intubation care. RESULTS: Immune system status in peripheral whole blood provides a sensitive and responsive sentinel signal reflecting how different functional pathways are currently being regulated in a subject. Deciphering this signal status of how immune cells are set to respond provides deep functional information regarding patient health and potential disease phenotypes resulting from a cytokine storm characteristic of a hyper immune inflammatory response to COVID-19 infection. CONCLUSIONS: The ability to identify future potential changes in patient health using this novel EpiMarker technology opens new avenues for defending populations from severe disease risks of Acute Respiratory Distress Syndrome. POLICY IMPLICATIONS: A successful EpiMarker Assay for COVID-19 disease severity risk would allow for two important applications: (1) patients could be triaged early in the course of infection to allow for critical decisions for allocating resources, both in terms of hospital infrastructure (ICU beds, ventilators) and therapeutic drug treatments; and (2) pre-infection, individuals could be screened to identify personnel at low-risk for mission critical assignments (first responders, doctors, nurses, military personnel, etc.) during future pandemics and ongoing battles with viral pathogens like influenza.
