Access Profiling systemic physiology through blood-based multidimensional

ABSTRACT

The physiology of critical care patients is more complex than normally appreciated. Patients arrive at the intensive care unit (ICU) or the pediatric ICU (PICU) with a variety of infections, trauma, organ damage, and dysfunctional immune systems. This population is the prime target for testing and applying new precision medicine tools to decipher the unique biology occurring within each patient. This is particularly important as COVID-19 has made such an impact on the United States healthcare system. Thus, there is a need to develop strategies to find multiple levels of information while minimizing the number of tests performed, shifting the balance of testing to more proactive than reactive. With the collection of ∼2mL of blood (about half a teaspoon), our collaboration between Spectrum Health and Michigan State University has shown the ability to use PAXgene tubes and RNAseq to simultaneously map human gene/transcript signatures, score panels of corresponding risk genes, deconvolute immune cells, detect markers of organ/cell damage, detect RNA from bacteria/viruses/plants/fungi, profile the immune repertoire, address how patients are unique from other samples, and address common/rare genetic mutations. These tools have been applied to three cohorts of patients (and age matched controls) for critical care medicine physiology understanding for nearly all ages 1) Infants with Respiratory syncytial virus (RSV);2) Kids with multiple organ dysfunction syndrome;and 3) Adults with hospitalized or lethal COVID-19. Our findings from these tools shows the complexity of immune system activation, secondary infections, and under appreciated interactions of the immune cell disorder overlapping COVID-19 pathology. The promise of blood-based transcriptomics to reveal cellular and cell free signatures opens a door for building more detailed physiological mechanisms from precision medicine.